I missed a Dimia tablet, what should I do? Instructions for use of Dimia

Content

Combined oral contraceptives are one of the most popular and sought-after types of protection against unwanted pregnancy. The use of such tablets is prescribed exclusively by a gynecologist, and the patient is monitored. “Dimia” becomes a good option for contraceptives - the instructions for using the drug will tell you in detail about the nuances of its effects, contraindications and other features of administration.

Manufacturer Dimia

The hormonal drug is produced by the world-famous company Gedeon Richter. This company has been working in the pharmaceutical field since 1901, the same year it was founded. The company is based in Hungary, in the city of Budapest. The company produces not only hormonal contraception, but also other drugs. Particular attention is paid to the following areas of medicine:

• women Health;
• neurology;
• cardiovascular problems;
• over-the-counter drugs.

Dimia contraceptive pills are of high quality, however, they must be taken according to the indications and instructions for use. Gedeon Richter is the choice of people who trust time-tested professional pharmaceuticals.

Pharmacotherapeutic group and properties

The medicine belongs to the group of combined contraceptives aimed at protecting against unwanted pregnancy. This pharmacotherapeutic group includes drugs based on two active ingredients - gestagen and estrogen. The pharmacodynamic and pharmacokinetic properties of the drug are as follows:

1. Antimineralocorticoid effect - prevents weight gain and prevents fluid retention in the body.
2. Antiandrogenic effect – suppression of the effects of androgens on the body.
3. Suppression of ovulation.
4. Changes in the properties of cervical secretion.
5. Improving the regularity of the menstrual cycle.

The drug "Dimia" is quickly absorbed, regardless of food intake. The substance is eliminated through the kidneys and intestines after 40 hours. When used correctly according to the instructions, the tablets help relieve the painful condition of a woman before her period.

Composition of Dimia

Effective COCs "Dimia" are produced in tablet form. The pack contains 28 tablets, 24 of which contain active substances, and the remaining 4 green tablets are auxiliary. You can often find the name “Dimia” 24 + 4, which indicates the number of active and inactive tablets.

Important! The inactive pills in contraceptives are intended to regulate the menstrual cycle.

In the instructions for use you can find the following information about the composition:

• drospirenone is an active substance that has an antiandrogenic effect;
• ethinyl estradiol - a synthetic analogue of estradiol, promotes thickening of the endometrium;
• lactose monohydrate – used to fill tablets;
• corn starch – holds the components of the drug together;
• macrogol and polyvinyl alcohol copolymer - help the tablet dissolve in water;
• Magnesium stearate – gives tablets their shape.

Each tablet contains 3 mg of drospirenone and 0.02 mg of ethinyl estradiol. Inactive tablets consist of cellulose, starch, magnesium stearate and silicon dioxide.

Indications for use

Only a gynecologist prescribes the use of tablets, regardless of the reason for which Dimia was prescribed. You can start taking pills on your own only after you have fully read the instructions for use.

The main indication for taking a contraceptive will be the ability to protect against unwanted pregnancy. The drug is used as oral contraception - it must be taken orally with water. Doctors often prescribe the drug for medicinal purposes - to correct hormonal levels and eliminate pain before menstruation. You can learn more about the readings from the video

Contraindications to Dimia

Most hormonal contraceptives have contraindications. All prohibitions are indicated in the instructions; if the patient exhibits negative symptoms or develops these conditions after taking the pills, the pills are canceled.

Contraindications to contraceptives "Dimia":

• venous thromboembolism;
• arterial thromboembolism;
• severe liver disease;
• acute or chronic renal failure;
• bleeding from the vagina for unknown reasons;
• the presence of malignant liver tumors;
• the presence of hormone-dependent tumors;
• pregnancy.

The indicated conditions must be present in the anamnesis, then the use of Dimia is prohibited.

Attention! If side effects are observed at the start of treatment, the gynecologist cancels contraception.

How to take Dimia

Start taking the product according to the instructions for use with water. The drug must be taken every day at the same time, following the arrows on the blister. The drug is designed for a menstrual cycle of 28 days, so it contains exactly 28 tablets.

How to take Dimia for the first time

If no oral contraceptives have been used in the past month, then the medicine is taken with the first tablet from the first day of the menstrual cycle. The woman chooses a convenient time for her when it is best to take the drug. Now this will need to be done daily.

It is necessary to constantly monitor the intake according to the instructions and not to miss active pills, otherwise you will have to take additional contraceptives. Dimia hormonal tablets begin to act from the first dose, so you can forget about condoms and other methods of protection against unwanted pregnancy.

How to take Dimia green tablets

Tablets colored green do not contain the active substances drospirenone and ethinyl estradiol. On the blister they are located along the arrows, starting with the 25th tablet and ending with the 28th tablet. After the 24th day of the cycle, the reliability of active tablets decreases, so the manufacturer uses a placebo.

Comment! Placebo tablets are necessary to ensure that you do not miss your daily dose of the drug.

Missing 1 green Dimia tablet does not entail anything. If you still missed one inactive tablet, it is recommended not to use it, but simply throw it away. This move will help you avoid confusion when taking the drug further. You often get your period after taking a placebo.

What to do if you missed a Dimia tablet

There are several rules that will help a woman act competently if she missed the Dimia pill. The missed tablet must be taken as soon as the woman remembers it, however, do not forget that the maximum dosage of the drug according to the instructions is no more than two units per day.

Depending on the day of the pass, the following recommendations will apply:

1. Days 1-7: the tablet is taken as soon as you remember it. Next, the drug is taken according to the established schedule. In addition, it is necessary to use a barrier method of contraception for the next 7 days.
2. Days 8-14: The tablet is taken immediately, even if you need to drink 2 units at the same time. If the medicine was taken according to the regimen a week before the missed dose, then there is no need to take additional protection.
3. Days 15-24: Take the tablet immediately, even if you need to take 2 tablets. If the dosage regimen was followed 7 days before the missed date, additional contraception will not be required. If there were the same gaps before, then it is recommended not to take inactive tablets from the last row, but to start a new pack.

Advice! By following the instructions for using Dimia tablets and following the recommended regimen when missed, you can prevent unwanted pregnancy.

How much can you drink Dimia without a break?

In numerous sources you can find information that taking hormonal contraceptives is harmful to a woman’s health with long-term use. The instructions for the drug say the opposite: they can be taken for a long period of time.

You can take the drug without interruption, like other combined hormonal drugs for a long time. Some women take the medicine for 5 years and feel great: the menstrual cycle improves, the pain goes away, there is no need to think about additional contraception. The drug is not suitable for other women, side effects occur, and the doctor discontinues the drug.

When you can not use protection with Dimia

The hormonal drug "Dimia" was created to ensure that sexual partners do not use protection during sex. But the tablets will be effective only in the following cases:

• in full compliance with the instructions for use;
• in the absence of contraindications;
• in the absence of gaps.

If a girl begins to skip doses of the drug, there is a high chance of pregnancy: then the use of additional barrier-type contraceptives cannot be avoided. If the patient strictly follows the dosage regimen, you can forget about condoms.

Pregnancy after Dimia

Conception after taking it occurs during the period of drug withdrawal. As a rule, the lack of protection makes itself felt: unprotected sexual intercourse threatens an early pregnancy. However, doctors do not recommend rushing with fertilization, because the body is in a stage of hormonal stress after stopping oral contraception.

According to reviews from girls, pregnancy after discontinuation occurred in the 2nd month, although doctors recommend waiting at least 3-4 months. This is necessary so that the female body can rest and recover after taking hormones. By allowing the body to adjust to its previous hormonal levels, a woman contributes to natural preparation for conception.

Side effects of Dimia

The manufacturer indicates in the instructions that side effects may occur during use. The likelihood of their occurrence is small, but still a small percentage exists:

1. Gastrointestinal tract: weight gain, anorexia, nausea, diarrhea, increased appetite.
2. Allergic reactions from the immune system.
3. Nervous system: changeable mood, headaches, dizziness, nervousness, insomnia, rarely – lack of orgasm.
4. Vascular: migraine, varicose veins, rarely – fainting.
5. Reproductive system: chest pain, lack of menstruation after withdrawal, pelvic pain, painful menstruation.

According to statistics, some women experienced venous and arterial thromboembolic diseases.

Is it possible to gain weight from Dimia?

It is necessary to purchase and use hormonal contraceptives only as prescribed by a doctor and according to the instructions for use. This helps avoid unwanted side effects such as weight gain. According to statistics, hormonal pills "Dimia" in rare cases can cause weight gain.

Women note a slight increase in appetite, which contributes to a weight gain of 2-3 kg. However, not every girl experiences this side effect. Some patients do not notice that weight gain occurred for another reason, however, they associate this phenomenon with taking the drug. According to reviews, the weight gained in the first month after taking it was subsequently successfully eliminated.

Chest hurts from Dimia

Another most common side effect is breast pain. This phenomenon occurs for the following reasons:

• breast enlargement;
• approaching menstruation;
• presence of breast diseases.

If all the tests performed have shown that the listed conditions are absent and the chest hurts precisely from birth control pills, the doctor should cancel it and prescribe the patient another drug. Chest pain may be associated with hormonal changes and adaptation, then they disappear the next month and the woman continues treatment.

Special instructions and precautions

It is necessary to take contraception only according to the instructions, which also indicate special cases when caution should be exercised:

• smoking women under 35 years of age;
• tendency to obesity;
• arterial hypertension;
• migraine;
• heart defects;
• predisposition to thrombosis.

All of these conditions can lead to thromboembolism, which significantly worsens the patient’s condition when taking the medication. In addition, those women who have developed various diseases after taking other COCs should take the drug with caution.

Drug interactions

Many girls are interested in the issue of interactions with other medications. The manufacturer provides the following information in the instructions for use:

1. Primidone, barbiturates and phenytoin weaken the contraceptive effect. This also includes preparations containing St. John's wort.
2. Substances that increase or decrease the concentration of estrogen - inhibitors of HIV or hepatitis C virus proteases.
3. Drugs containing itraconazole, clarithromycin, erythromycin, and grapefruit juice can increase the concentration of estrogen in the blood plasma.

Important! While taking medications that reduce the effect, you should consult your doctor for possible additional prescription of other contraceptives.

Dimia and alcohol

The compatibility of Dimia and alcohol should not raise doubts, because both substances are absorbed and processed separately. However, with simultaneous use, there is a heavy load on the liver, where processing occurs. You should not take Dimia and alcohol for the following reasons:

• increased side effects may occur;
• The effectiveness of the drug may decrease.

If it is impossible to give up alcohol in certain situations, then it is recommended to take alcohol 3 hours after the pill.

Dimia and smoking

As mentioned above, smoking is not advisable for women under 35 years of age while taking contraceptives. This combination not only harms the woman’s general health, but also increases the risk of thrombosis. Women who have a history of problems with blood vessels need to be extremely careful, because smoking impedes the movement of blood through the veins. All listed risks can be read in the instructions for use.

Terms and conditions of storage

Dimia tablets, photos of which can be seen in this material, are sold in pharmacies with a prescription. Storage recommendations will be as follows:

• storage is carried out for no more than 2 years;
• the drug must be stored in a dark place;
• It is not allowed to store the contraceptive in a place accessible to children.

After the shelf life has expired, the medicine cannot be used, as indicated in the instructions for use. Expiration dates can be seen on the package of the drug, as well as on the blister of tablets.

Dimia price in pharmacies

The cost of Dimia will vary depending on the place of sale: you can buy the drug in city pharmacies and online. Hormonal pills are sold in small and large packs, designed for several months of use:

1. 28 pieces in a pack - from 640 to 720 rubles.
2. 84 pieces in a pack - from 1600 to 1800 rubles.

It is recommended to purchase a large pack if the woman has gone through the adaptation period without side effects. For medicinal purposes, a doctor may prescribe the drug for six months, so a large pack is designed for half of this period.

Dimia's analogs

Substitutes for the drug should be based on a similar active ingredient - ethinyl estradiol. Such drugs include:

• "Yarina";
• "Belar";
• "Silhouette";
• "Lindynet 20".

Dimia or Belara: which is better

The drug "Belara" contains ethinyl estradiol and chlormadinone. If the first component is a synthetic analogue of the female hormone, then chlormadinone in the drug is responsible for the antiandrogenic effect. Contraindications to the drug are the same as for Dimia - they are indicated in the instructions for use.

Gynecologists can transfer a patient from Dimia to Belara if individual side effects occur. "Belara" has the same cost as "Dimia".

Dimia or Silhouette: which is better

The composition of the drug "Silhouette" contains a combination of the substances ethinyl estradiol and dienogest - a gestagen close in origin to progesterone. "Silhouette" is prescribed not only for oral contraception, but also for the treatment of acne associated with hormones.

“Silhouette” will be similar to “Dimia”, only cheaper. It can be purchased from 600 rubles per pack of 21 pieces. There is a slightly different method of administration here: when all the tablets are taken, a seven-day break is taken, after which they begin to take the next pack. According to the instructions for use, your period comes during this break.

Dimia or Lindinet 20: which is better?

"Lindinet 20" in addition to ethinyl estradiol, contains gestodene - a progestogen. There are no auxiliary inactive tablets; each tablet contains an active ingredient: more details can be found in the instructions for use. Lindinet 20, like Dimia, is prescribed for oral contraception.

Lindinet 20 has a lower cost than Dimia, so gynecologists often prescribe it to women who have decided to use oral contraception for the first time. Over time, the doctor may recommend switching to Dimia.

Dimia or Yarina: which is better

COCs "Yarina" are one of the most common drugs used not only for contraception, but for medicinal purposes. "Yarina" is prescribed for:

• normalization of the menstrual cycle;
• treatment of endometriosis;
• treatment of cysts;
• eliminating pain in the first days of menstruation.

Yarina also contains drospirenone and ethinyl estradiol. The drugs are equally well tolerated by patients, so they are prescribed interchangeably.

Conclusion

The hormonal drug "Dimia", the instructions for use of which will tell you how to take the pills correctly, is prescribed to young girls and women for contraception. Compliance with all rules and dosage regimens guarantee the absence of unwanted pregnancy.

white or off-white, round, biconvex, embossed with "G73" on one side of the tablet; On a cross section, the core is white or almost white.

Excipients: lactose monohydrate - 48.53 mg, corn starch - 16.6 mg, pregelatinized corn starch - 9.6 mg, copolymer of macrogol and polyvinyl alcohol - 1.45 mg, magnesium stearate - 0.8 mg.

Film shell composition: opadry II white 85G18490 - 2 mg (polyvinyl alcohol - 0.88 mg, titanium dioxide - 0.403 mg, macrogol 3350 - 0.247 mg, talc - 0.4 mg, soy lecithin - 0.07 mg).

Placebo tablets

Film-coated tablets green, round, biconvex; On a cross section, the core is white or almost white.

Excipients: microcrystalline cellulose - 42.39 mg, lactose - 37.26 mg, pregelatinized corn starch - 9 mg, magnesium stearate - 0.9 mg, colloidal silicon dioxide - 0.45 mg.

Film shell composition: opadry II green 85F21389 - 3 mg (polyvinyl alcohol - 1.2 mg, titanium dioxide - 0.7086 mg, macrogol 3350 - 0.606 mg, talc - 0.444 mg, indigo carmine - 0.0177 mg, quinoline yellow dye - 0.0177 mg, iron oxide dye black - 0.003 mg , sunset yellow dye - 0.003 mg).

28 pcs. - blisters (1) - cardboard packs.
28 pcs. - blisters (3) - cardboard packs.

The description of the drug is based on the official instructions for use and approved by the manufacturer.

pharmachologic effect

Dimia ® is a combined monophasic oral contraceptive containing drospirenone and ethinyl estradiol. In terms of its pharmacological profile, drospirenone is close to natural progesterone: it does not have estrogenic, glucocorticoid and antiglucocorticoid activity and is characterized by pronounced antiandrogenic and moderate antimineralocorticoid effects. The contraceptive effect is based on the interaction of various factors, the most important of which are inhibition of ovulation, increased viscosity of cervical secretions and changes in the endometrium. The Pearl index, an indicator reflecting the pregnancy rate in 100 women of reproductive age during a year of contraceptive use, is less than 1.

Pharmacokinetics

Drospirenone

Suction

When taken orally, drospirenone is rapidly and almost completely absorbed from the gastrointestinal tract. Cmax of drospirenone in serum is about 38 ng/ml and is achieved approximately 1-2 hours after a single dose.

Bioavailability - 76-85%. Concomitant use with food does not affect the bioavailability of drospirenone.

Distribution

After oral administration, plasma concentrations of drospirenone decreased with a final half-life of 31 hours. Drospirenone binds to serum albumin and does not bind to sex hormone-binding globulin (SHBG) or corticosteroid-binding globulin (transcortin). Only 3-5% of total serum concentrations of drospirenone exist as free steroids. The ethinyl estradiol-induced increase in SHBG does not affect the binding of drospirenone to serum proteins. The average apparent Vd of drospirenone is 3.7±1.2 l/kg.

During the treatment cycle, C ss max of drospirenone in blood plasma is about 70 ng/ml, it is achieved after 8 days of treatment. Serum concentrations of drospirenone increase approximately 3-fold due to the ratio of final half-life and dosing interval.

Metabolism

Drospirenone is actively metabolized after oral administration. The main metabolites in the blood plasma are the acidic forms of drospirenone, formed during the opening of the lactone ring, and 4,5-dihydro-drospirenone-3-sulfate, both formed without the participation of the P450 system. Drospirenone is slightly metabolized by CYP3A4 and is capable of inhibiting this enzyme, as well as CYP1A1, CYP2C9 and CYP2C19 in vitro.

Removal

Renal clearance of drospirenone metabolites in blood serum is 1.5±0.2 ml/min/kg. Drospirenone is excreted only in trace amounts unchanged. Drospirenone metabolites are excreted by the kidneys and intestines with an excretion ratio of about 1.2:1.4. T1/2 of metabolites by the kidneys and through the intestines is about 40 hours.

Ethinyl estradiol

Suction

When taken orally, ethinyl estradiol is absorbed quickly and completely. Cmax in blood serum is about 33 pkg/ml and is achieved within 1-2 hours after a single oral dose. Absolute bioavailability as a result of first pass conjugation and first pass metabolism is approximately 60%. Concomitant food intake decreased the bioavailability of ethinyl estradiol in approximately 25% of the patients studied; others had no changes.

Distribution

Serum concentrations of ethinyl estradiol decreased biphasically, in the final distribution phase T1/2 is approximately 24 hours. Ethinyl estradiol binds well, but nonspecifically, to serum albumin (approximately 98.5%) and induces an increase in serum concentrations of SHBG. Apparent V d - about 5 l/kg.

C ss is achieved in the second half of the treatment cycle, and the serum concentration of ethinyl estradiol increases by 2-2.3 times.

Metabolism

Ethinyl estradiol is a substrate of presystemic conjugation in the mucous membrane of the small intestine and in the liver. Ethinyl estradiol is primarily metabolized by aromatic hydroxylation, resulting in a wide range of hydroxylated and methylated metabolites, which are present both in free form and as conjugates with glucuronic acid. Renal clearance of ethinyl estradiol metabolites is approximately 5 ml/min/kg.

Removal

Unchanged ethinyl estradiol is practically not excreted from the body. Metabolites of ethinyl estradiol are excreted by the kidneys and through the intestines in a ratio of 4:6. T1/2 of metabolites is about 24 hours.

Pharmacokinetics in special clinical situations

If kidney function is impaired

Css of drospirenone in blood plasma in women with mild renal failure (creatinine clearance 50-80 ml/min) was comparable to the corresponding values ​​in women with normal renal function (creatinine clearance > 80 ml/min). In women with moderate renal failure (creatinine clearance from 30 ml/min to 50 ml/min), the plasma concentration of drospirenone was on average 37% higher than in women with normal renal function. Drospirenone was well tolerated in all groups. Taking drospirenone did not have a clinically significant effect on serum potassium levels. Pharmacokinetics in severe renal failure have not been studied.

In case of liver dysfunction

Drospirenone is well tolerated by patients with mild to moderate hepatic impairment (Child-Pugh class B). Pharmacokinetics in severe hepatic impairment have not been studied.

Indications

- oral contraception.

Dosage regimen

The tablets should be taken daily, at approximately the same time, with a small amount of water, in the order indicated on the blister pack. The tablets are taken continuously for 28 days, 1 tablet/day. Taking tablets from the next package begins after taking the last tablet from the previous package. Withdrawal bleeding usually begins 2-3 days after starting placebo tablets (last row) and does not necessarily end by the start of the next pack.

How to start taking Dimia ®

If hormonal contraceptives have not been used in the last month, Taking Dimia ® begins on the first day of the menstrual cycle (i.e., on the first day of menstrual bleeding). It is possible to start taking it on days 2-5 of the menstrual cycle; in this case, additional use of a barrier method of contraception is necessary during the first 7 days of taking the tablets from the first package.

Switching from other combined contraceptives (combined oral contraceptives in pill form, vaginal ring or transdermal patch)

You should start taking Dimia ® the next day after taking the last inactive tablet (for preparations containing 28 tablets) or the next day after taking the last active tablet from the previous package (possibly the next day after the end of the usual 7-day break) - for drugs containing 21 tablets per package. If a woman uses a vaginal ring or transdermal patch, it is preferable to start taking Dimia ® on the day of their removal or, at the latest, on the day when a new ring is planned to be inserted or the patch is replaced.

Switching from contraceptives containing only progestogens (mini-pills, injections, implants), or from an intrauterine system (IUD) that releases progestogens.

A woman can switch from taking a mini-pill to taking Dimia ® on any day (from an implant or IUD on the day of their removal, from injectable forms of drugs - on the day when the next injection was due), but in all cases it is necessary to use additionally a barrier method of contraception during the first 7 days of taking the pills.

After an abortion in the first trimester of pregnancy

Taking Dimia ® can be started as prescribed by a doctor on the day of termination of pregnancy. In this case, the woman does not need to take additional contraceptive measures.

After childbirth or abortion in the second trimester of pregnancy.

A woman is recommended to start taking the drug 21-28 days after childbirth (provided she is not breastfeeding) or abortion in the second trimester of pregnancy. If use is started later, the woman should use an additional barrier method of contraception during the first 7 days after starting to take Dimia ® . With the resumption of sexual activity (before starting to take Dimia ®), pregnancy should be excluded.

Taking missed pills

Skipping a placebo tablet from the last (4th) row of the blister can be ignored. However, they should be discarded to avoid inadvertently prolonging the placebo phase. The instructions below only apply to missed tablets containing active ingredients.

If the delay in taking the pill is less than 12 hours, contraceptive protection is not reduced. A woman should take the missed pill as soon as possible (as soon as she remembers), and the next pill at the usual time.

If you are late exceeds 12 hours, contraceptive protection may be reduced. In this case, you can be guided by two basic rules:

1. Taking pills should never be interrupted for more than 7 days;

2. To achieve adequate suppression of the hypothalamic-pituitary-ovarian axis, 7 days of continuous pill use are required.

In accordance with this, women can be given the following recommendations:

Days 1-7

A woman should take the missed pill as soon as she remembers, even if this means taking two pills at the same time. She should then take the pills at the usual time. Additionally, a barrier method such as a condom should be used for the next 7 days. If sexual intercourse occurred in the previous 7 days, the possibility of pregnancy should be considered. The more pills you miss and the closer this skip is to the 7-day break in taking the drug, the higher the risk of pregnancy.

Days 8-14

A woman should take the missed pill as soon as she remembers, even if this means taking two pills at the same time. She should then take the pills at the usual time. If during the 7 days preceding the first missed pill, a woman took her pills as prescribed, there is no need for additional contraceptive measures. However, if she missed more than 1 tablet, an additional method of contraception (barrier - for example, a condom) is required for 7 days.

Days 15-24

The reliability of the method inevitably decreases as the placebo pill phase approaches. However, adjusting your pill regimen can still help prevent pregnancy. When following one of the two regimens described below, and if in the previous 7 days before skipping the pill the woman complied with the drug regimen, there will be no need to use additional contraceptive measures. If this is not the case, she should follow the first of two regimens and use additional precautions for the next 7 days.

1. A woman should take the last missed pill as soon as she remembers, even if this means taking two pills at the same time. She should then take the tablets at the usual time until the active tablets are gone. 4 placebo tablets from the last row should not be taken; you should immediately start taking tablets from the next blister pack. Most likely, there will be no withdrawal bleeding until the end of the second package, but spotting or withdrawal bleeding may occur on the days of taking the drug from the second package.

2. A woman can also stop taking active tablets from the started package. Instead, she should take placebo tablets from the last row for 4 days, including the days she missed tablets, and then start taking tablets from the next pack.

If a woman misses a pill and subsequently does not experience withdrawal bleeding during the placebo pill phase, the possibility of pregnancy should be considered.

Use of the drug for gastrointestinal disorders

In case of severe gastrointestinal disorders (for example, vomiting or diarrhea), absorption of the drug will be incomplete and additional contraceptive measures will be required. If vomiting occurs within 3-4 hours after taking the active tablet, you must take a new (replacement) tablet as quickly as possible. If possible, the next tablet should be taken within 12 hours of the usual tablet-taking time. If more than 12 hours have passed, it is recommended to proceed as directed when missing tablets. If a woman does not want to change her usual pill regimen, she should take an additional pill from a different pack.

Delay of menstrual-like withdrawal bleeding

To delay bleeding, the woman should skip the placebo tablets from the started pack and start taking drospirenone + ethinyl estradiol tablets from the new pack. The delay can be extended until the active tablets in the second package run out. During the delay, a woman may experience acyclic heavy or spotting bleeding from the vagina. Regular use of Dimia ® is resumed after the placebo phase.

To shift bleeding to another day of the week, it is recommended to shorten the upcoming phase of taking placebo tablets by the desired number of days. When the cycle is shortened, it is more likely that the woman will not have menstrual-like “withdrawal” bleeding, but will have acyclic heavy or spotting bleeding from the vagina when taking the next package (the same as when the cycle is lengthened).

Side effect

The following adverse events have been reported while taking Dimia ®:

Organ system class	Frequent (≥1/100 to< 1/10)	Less frequent (≥1/1000 to< 1/100)	Rare (≥ 1/10,000 to< 1/1000)
Infections and infestations			candidiasis, incl. oral cavity
From the blood and lymphatic system			anemia, thrombocytopenia
From the immune system			allergic reactions
Metabolism and nutrition		weight gain	increased appetite, anorexia, hyperkalemia, hyponatremia, weight loss
From the mental side	emotional lability	depression, decreased libido, nervousness, drowsiness	anorgasmia, insomnia
From the nervous system	headache	dizziness, paresthesia	vertigo, tremor
From the side of the organ of vision			conjunctivitis, dryness of the mucous membrane of the eye, visual impairment
From the cardiovascular system		migraine, phlebeurysm, increased blood pressure	tachycardia, phlebitis, vascular damage, nose bleed, fainting
From the digestive system	nausea, abdominal pain	vomit, diarrhea
From the liver and biliary tract			gallbladder pain, cholecystitis
From the skin and subcutaneous tissue		rash (including acne), itching	chloasma, eczema, alopecia, acne dermatitis, dry skin, erythema nodosum, hypertrichosis, skin lesions, cutaneous stretch marks, contact dermatitis, photodermatitis, skin nodules
From the musculoskeletal system		backache, pain in the limbs, muscle cramps
From the reproductive system and mammary glands	chest pain, no withdrawal bleeding	vaginal candidiasis, pelvic pain, enlargement of the mammary glands, fibrocystic breast disease, vaginal discharge, rushes of blood, vaginitis, acyclic bleeding, painful menstrual-like bleeding, heavy withdrawal bleeding scanty menstrual-like bleeding, dryness of the vaginal mucosa, change in the cytological picture in the Pap smear	painful sexual intercourse, vulvovaginitis, postcoital bleeding, breast cyst, breast hyperplasia, mammary cancer, cervical polyps, endometrial atrophy, ovarian cyst, enlarged uterus
Are common disorders		asthenia, increased sweating, edema (generalized edema, peripheral edema, facial edema)	feeling of discomfort

The following serious adverse events have been reported in women using combined oral contraceptives (COCs):

- venous thromboembolic diseases;

- arterial thromboembolic diseases;

- liver tumors;

- the occurrence or exacerbation of conditions for which the connection with taking COCs has not been proven: Crohn's disease, ulcerative colitis, epilepsy, migraine, endometriosis, uterine fibroids, porphyria, systemic lupus erythematosus, herpes during previous pregnancy, rheumatic chorea, hemolytic-uremic syndrome, cholestatic jaundice;

- chloasma;

- acute or chronic liver diseases may necessitate discontinuation of COCs until liver function tests are normalized;

- In women with hereditary angioedema, exogenous estrogens can induce or worsen the symptoms of angioedema.

Contraindications

Dimia ®, like other combined oral contraceptives, is contraindicated in any of the following conditions:

- thrombosis (arterial and venous) and thromboembolism currently or in history (including thrombosis, deep vein thrombophlebitis; pulmonary embolism, myocardial infarction, stroke, cerebrovascular disorders);

- conditions preceding thrombosis (including transient ischemic attacks, angina) currently or in history;

- multiple or pronounced risk factors for venous or arterial thrombosis, incl. complicated lesions of the valvular apparatus of the heart, atrial fibrillation, diseases of the cerebral vessels or coronary arteries; uncontrolled arterial hypertension, major surgery with prolonged immobilization, smoking over the age of 35 years, obesity with a BMI >30 kg/m2;

- hereditary or acquired predisposition to venous or arterial thrombosis, for example, resistance to activated protein C, antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and antibodies against phospholipids (presence of antibodies to phospholipids - antibodies to cardiolipin, lupus anticoagulant);

- pancreatitis with severe hypertriglyceridemia currently or in history;

- existing severe liver disease (or history) provided that liver function is not currently normalized;

- severe chronic or acute renal failure;

- liver tumor (benign or malignant) currently or in history;

- hormone-dependent malignant neoplasms of the genital organs or breast, currently or in history;

- bleeding from the vagina of unknown origin;

- migraine with focal neurological symptoms in history;

- lactase deficiency, lactose intolerance, glucose-galactose malabsorption, lapp lactase deficiency (lactase deficiency in some peoples of the North);

- pregnancy and suspicion of it;

- lactation period;

- hypersensitivity to the drug or any of the components of the drug.

WITH caution

- risk factors for the development of thrombosis and thromboembolism: smoking under the age of 35, obesity, dyslipoproteinemia, controlled arterial hypertension, migraine without focal neurological symptoms, uncomplicated valvular heart disease, hereditary predisposition to thrombosis (thrombosis, myocardial infarction or cerebrovascular accident at a young age from any of the immediate relatives);

- diseases in which peripheral circulatory disorders may occur: diabetes mellitus without vascular complications, systemic lupus erythematosus (SLE), hemolytic-uremic syndrome, Crohn's disease, ulcerative colitis, sickle cell anemia, phlebitis of the superficial veins;

- hereditary angioedema;

- hypertriglyceridemia;

- severe liver disease (until normalization of liver function tests);

- diseases that first appeared or worsened during pregnancy or against the background of previous use of sex hormones (including jaundice and/or itching associated with cholestasis, cholelithiasis, otosclerosis with hearing impairment, porphyria, history of herpes during pregnancy, minor chorea (Sydenham disease), chloasma;

- postpartum period.

Use during pregnancy and breastfeeding

Dimia ® is contraindicated during pregnancy.

If pregnancy occurs while using the drug Dimia ®, its use should be stopped immediately. Extensive epidemiological studies have found neither an increased risk of birth defects in children born to women who took COCs before pregnancy, nor a teratogenic effect of COCs if taken unintentionally during pregnancy.

According to preclinical studies, it is impossible to exclude undesirable effects that affect the course of pregnancy and fetal development due to the hormonal action of the active components.

The drug Dimia ® can affect lactation: reduce the amount of milk and change its composition. Small amounts of contraceptive steroids and/or their metabolites may be excreted in milk during COC use. These amounts may affect the child. The use of Dimia ® during breastfeeding is contraindicated.

special instructions

If you have any of the conditions/risk factors listed below, the benefits of taking COCs should be assessed individually for each woman and discussed with her before starting use. If an adverse event worsens or if any of these conditions or risk factors occur, the woman should contact her doctor. The doctor must decide whether to stop taking the COC.

Circulatory disorders

Taking any combined oral contraceptive increases the risk of venous thromboembolism (VTE). The increase in the risk of VTE is most pronounced in the first year of a woman's use of a combined oral contraceptive.

Epidemiological studies have shown that the incidence of VTE in women with no risk factors who took low doses of estrogens (<0.05 мг этинилэстрадиола) в составе комбинированного перорального контрацептива, составляет примерно 20 случаев на 100 000 женщин-лет (для левоноргестрелсодержащих КПК "второго поколения") или 40 случаев на 100 000 женщин-лет (для дезогестрел/гестоденсодержащих КПК "третьего поколения"). У женщин, не пользующихся КПК, случается 5-10 ВТЭ и 60 беременностей на 100 000 женщин-лет. ВТЭ фатальна в 1-2% случаев.

Data from a large, prospective, 3-arm study showed that the incidence of VTE in women with or without other risk factors for venous thromboembolism using the combination of ethinyl estradiol and drospirenone, 0.03 mg + 3 mg, was the same as the incidence of VTE in women using levonorgestrel-containing oral contraceptives and other PDAs. The degree of risk of venous thromboembolism when taking Dimia ® has not currently been established.

Epidemiological studies have also revealed an association between COC use and an increased risk of arterial thromboembolism (myocardial infarction, transient ischemic events).

Very rarely, thrombosis of other blood vessels, such as veins and arteries of the liver, mesentery, kidney, brain or retina, has occurred in women taking oral contraceptives. There is no consensus regarding the connection of these phenomena with the use of hormonal contraceptives.

Symptoms of venous or arterial thrombotic/thromboembolic events or acute cerebrovascular accidents:

- unusual unilateral pain and/or swelling of the lower extremities;

- sudden severe pain in the chest, regardless of whether it radiates to the left arm or not;

- sudden shortness of breath;

- sudden onset of cough;

- any unusual, severe, prolonged headache;

- sudden partial or complete loss of vision;

- diplopia;

- impaired speech or aphasia;

- vertigo;

- collapse with or without partial epileptic seizures;

- weakness or very noticeable numbness that suddenly affects one side or part of the body;

- movement disorders;

- "sharp" stomach.

Before starting to take COCs, a woman should consult a specialist.

Risk venous thromboembolic disorders

- increasing age;

- hereditary predisposition (venous thromboembolism has ever occurred in siblings or parents at a relatively early age);

- prolonged immobilization, extended surgery, any surgery on the lower extremities or major trauma. In such situations, it is recommended to stop taking the drug (in the case of planned surgery, at least four weeks in advance) and not to resume until two weeks have passed after complete restoration of mobility. If the drug is not stopped promptly, anticoagulant treatment should be considered;

— obesity (body mass index more than 30 kg/m2);

— lack of consensus on the possible role of varicose veins and superficial thrombophlebitis in the appearance or exacerbation of venous thrombosis.

Risk arterial thromboembolic complications or acute cerebrovascular accident when taking COC increases with:

- increasing age;

- smoking (women over 35 years of age are strongly advised to quit smoking if they want to take COCs);

- dislipoproteinemia;

- arterial hypertension;

- migraine without focal neurological symptoms;

— obesity (BMI more than 30 kg/m2);

- hereditary predisposition (arterial thromboembolism ever in siblings or parents at a relatively early age). If a hereditary predisposition is possible, a woman should consult a specialist before starting to take COCs;

- damage to the heart valves;

- atrial fibrillation.

Having one major risk factor for venous disease or multiple risk factors for arterial disease may also be a contraindication. Anticoagulant therapy should also be considered. Women taking COCs should be properly instructed to inform their physician if symptoms of thrombosis are suspected. If thrombosis is suspected or confirmed, COC use should be discontinued. It is necessary to start adequate alternative contraception due to the teratogenicity of anticoagulant therapy (indirect anticoagulants - coumarin derivatives).

The increased risk of thromboembolism in the postpartum period should be taken into account.

Other medical conditions associated with adverse vascular events include diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis), and sickle cell disease.

An increase in the frequency or severity of migraine while taking COCs may be an indication for immediate discontinuation of combined oral contraceptives.

Tumors

The most significant risk factor for developing cervical cancer is infection with the human papillomavirus. Some epidemiological studies have reported an increased risk of cervical cancer with long-term use of combined oral contraceptives, but there remains controversy regarding the extent to which these findings are attributable to confounding factors such as testing for cervical cancer or use of barrier methods of contraception.

A meta-analysis of 54 epidemiological studies found a small increase in the relative risk (RR = 1.24) of breast cancer in women who were currently taking COCs. The risk gradually decreases over 10 years after stopping COC use. Since breast cancer rarely develops in women under 40 years of age, an increase in the number of breast cancer diagnoses among COC users has little effect on the overall likelihood of developing breast cancer. These studies did not find sufficient evidence of causality. The increased risk may result from earlier diagnosis of breast cancer in COC users, the biological effects of COCs, or a combination of both factors. Diagnosed breast cancer in women who had ever taken COCs was clinically less severe, which was due to early diagnosis of the disease.

Rarely, benign liver tumors and, even more rarely, malignant liver tumors have occurred in women taking COCs. In some cases, these tumors were life-threatening due to intra-abdominal bleeding. This should be taken into account when making a differential diagnosis in the event of severe abdominal pain, liver enlargement, or signs of intra-abdominal bleeding.

Other states

The progestogen component of the drug Dimia ® is an aldosterone antagonist that retains potassium in the body. In most cases, an increase in potassium levels is not expected. However, in a clinical study in some patients with mild to moderate kidney disease who were taking potassium-sparing medications, serum potassium levels increased slightly while taking drospirenone. Therefore, it is recommended to monitor serum potassium levels during the first cycle of treatment in patients with renal failure whose pre-treatment serum potassium concentrations were at the upper limit of normal and, especially, while taking potassium-sparing drugs.

Women with hypertriglyceridemia or a hereditary predisposition to it may have an increased risk of pancreatitis when taking COCs.

Although slight increases in blood pressure were observed in many women taking COCs, clinically significant increases were rare. Only in these rare cases is it justified to immediately stop taking the COC. If, when taking COCs in patients with concomitant arterial hypertension, blood pressure constantly increases or significantly elevated blood pressure cannot be corrected with antihypertensive drugs, taking COCs should be discontinued. After normalization of blood pressure with the help of antihypertensive drugs, COC use can be resumed.

The following diseases appeared or worsened both during pregnancy and when taking COCs, but the evidence of their relationship with taking COCs is inconclusive: jaundice and/or itching associated with cholestasis, gallstones; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; rheumatic chorea (Sydenham's chorea); herpes during pregnancy; otosclerosis with hearing loss.

In women with hereditary angioedema, exogenous estrogens may induce or worsen symptoms of edema.

Acute or chronic liver disease may be an indication to stop taking COCs until liver function tests normalize. Recurrence of cholestatic jaundice and/or pruritus associated with cholestasis, which developed during a previous pregnancy or with earlier use of sex hormones, is an indication for discontinuation of COCs.

Although COCs may influence peripheral insulin resistance and glucose tolerance, changing the treatment regimen in patients with diabetes mellitus while taking COCs with low hormone content (containing< 0.05 мг этинилэстрадиола) не показано. Однако следует внимательно наблюдать женщин с сахарным диабетом, особенно на ранних стадиях приема КПК.

While taking COCs, an increase in endogenous depression, epilepsy, Crohn's disease and ulcerative colitis was observed.

Chloasma may occur from time to time, especially in women who have a history of chloasma during pregnancy. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet light while taking COCs.

Drospirenone + ethinyl estradiol coated tablets contain 48.53 mg of lactose monohydrate, placebo tablets contain 37.26 mg of anhydrous lactose per tablet. Patients with rare hereditary diseases such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption who are on a lactose-free diet should not take this drug.

Women who are allergic to soy lecithin may experience allergic reactions.

The effectiveness and safety of Dimia ® as a contraceptive have been studied in women of reproductive age. It is assumed that in the postpubertal period up to 18 years of age, the effectiveness and safety of the drug are similar to those in women after 18 years of age. The use of the drug before menarche is not indicated.

Medical examinations

Before starting or re-using Dimia ®, obtain a complete medical history (including family history) and exclude pregnancy. It is necessary to measure blood pressure and conduct a medical examination, guided by contraindications and precautions. A woman should be reminded to carefully read the instructions for use and adhere to the recommendations contained therein. The frequency and content of the survey should be based on existing practice guidelines. The frequency of medical examinations is individual for each woman, but should be carried out at least once every 6 months.

Women should be reminded that oral contraceptives do not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Reduced efficiency

The effectiveness of COCs may be reduced, for example, if you miss a dose of drospirenone + ethinyl estradiol tablets, have gastrointestinal disorders while taking drospirenone + ethinyl estradiol tablets, or take other medications at the same time.

Insufficient cycle control

As with other COCs, a woman may experience acyclic bleeding (spotting or withdrawal bleeding), especially in the first months of use. Therefore, any irregular bleeding should be assessed after a three-month adaptation period.

If acyclic bleeding recurs or begins after several regular cycles, the possibility of developing disorders of a non-hormonal nature should be taken into account and measures should be taken to exclude pregnancy or cancer, including therapeutic and diagnostic curettage of the uterine cavity.

Some women do not experience withdrawal bleeding during the placebo phase. If the COC was taken in accordance with the instructions for use, then it is unlikely that the woman is pregnant. However, if the rules of administration were violated before the first missed menstrual-like withdrawal bleeding, or if two bleedings were missed, pregnancy should be excluded before continuing to take the COC.

Impact on the ability to drive vehicles and operate machinery

Not found.

Overdose

There have been no cases of overdose of Dimia ® yet. Based on general experience with combined oral contraceptives in potential symptoms overdose may include: nausea, vomiting, slight bleeding from the vagina.

Treatment: there are no antidotes. Treatment should be symptomatic.

Drug interactions

The influence of other drugs on the drug Dimia ®

Interactions between oral contraceptives and other drugs may result in acyclic bleeding and/or contraceptive failure. The interactions described below are reflected in the scientific literature.

Mechanism of interaction with hydantoin, barbiturates, primidone, carbamazepine and rifampicin; oxcarbazepine, topiramate, felbamate, ritonavir, griseofulvin and St. John's wort (Hypericum perforatum) preparations is based on the ability of these active substances to induce microsomal liver enzymes. Maximum induction of liver microsomal enzymes is not achieved within 2-3 weeks, but then persists for at least 4 weeks after cessation of drug therapy.

Contraceptive failure has also been reported with antibiotics such as ampicillin and tetracycline. The mechanism of this phenomenon is not clear.

Women during short-term treatment (up to one week) with any of the above groups of drugs or single drugs should temporarily use (while taking other drugs simultaneously and for another 7 days after its end), in addition to COCs, barrier methods of contraception.

Women receiving rifampin therapy other than COCs should use a barrier method of contraception and continue to use it for 28 days after stopping rifampin treatment. If the use of concomitant medications lasts longer than the expiration date of the active tablets in the package, the inactive tablets should be stopped and the drospirenone + ethinyl estradiol tablets from the next package should be started immediately.

If a woman is constantly taking drugs that induce microsomal liver enzymes, she should use other reliable non-hormonal methods of contraception.

The main metabolites of drospirenone in human plasma are formed without the participation of the cytochrome P450 system. Cytochrome P450 inhibitors are therefore unlikely to affect the metabolism of drospirenone.

Effect of Dimia ® on other drugs

Oral contraceptives may affect the metabolism of some other active ingredients. Accordingly, the concentrations of these substances in blood plasma or tissues may either increase (for example, cyclosporine) or decrease (for example, lamotrigine).

Based on in vitro inhibition studies and in vivo interaction studies in female volunteers taking omeprazole, simvastatin and midazolam as substrates, the effect of drospirenone 3 mg on the metabolism of other active substances is unlikely.

Other interactions

In patients without renal failure, simultaneous use of drospirenone and ACE inhibitors or NSAIDs does not have a significant effect on serum potassium levels. However, the simultaneous use of Dimia ® with aldosterone antagonists or potassium-sparing diuretics has not been studied. In this case, during the first cycle of treatment, the concentration of serum potassium should be monitored.

Laboratory tests

Taking contraceptive steroids may affect the results of some laboratory tests, including biochemical parameters of liver, thyroid, adrenal and kidney function, concentrations of plasma proteins (transporters), such as corticosteroid binding proteins and lipid/lipoprotein fractions, parameters of carbohydrate metabolism and blood coagulation parameters and fibrinolysis. In general, changes remain within the normal range. Drospirenone causes an increase in renin activity in the blood plasma and, due to a slight athymineralocorticoid activity, reduces the concentration of aldosterone in the plasma.

Conditions for dispensing from pharmacies

The drug is available with a prescription.

Storage conditions and periods

The drug should be stored out of the reach of children, protected from light at a temperature not exceeding 25°C. Shelf life - 2 years.

Compound

for 1 tablet:
Drospirenone + ethinyl estradiol tablets
active substance: drospirenone 3.000 mg, ethinyl estradiol 0.020 mg;
Excipients: lactose monohydrate, corn starch, pregelatinized corn starch, macrogol and polyvinyl alcohol copolymer, magnesium stearate.
Film casing (Opadray II white*): polyvinyl alcohol, titanium dioxide, macrogol-3350, talc, soy lecithin.
*code 85G18490
Placebo tablets
microcrystalline cellulose, lactose, pregelatinized corn starch, magnesium stearate, colloidal silicon dioxide.
Film casing (Opadray II green**): polyvinyl alcohol, titanium dioxide, macrogol-3350, talc, indigo carmine, quinoline yellow dye, black iron oxide dye; sunset yellow dye.
** code 85F21389

Description

For drospirenone + ethinyl estradiol tablets:
Round, biconvex, white or off-white film-coated tablets, embossed with "G73" on one side of the tablet. On a cross section, the core is white or almost white.
For placebo tablets:
Round, biconvex tablets, green film-coated. On a cross section, the core is white or almost white.

Pharmacotherapeutic group

combined contraceptive (estrogen + gestagen)

Pharmacological properties

Pharmacodynamics

The drug Dimia® is a combined hormonal contraceptive with antimineralocorticoid and antiandrogenic effects. The contraceptive effect of combined oral contraceptive drugs (COCs) is based on the interaction of various factors, the most important of which are suppression of ovulation and changes in the properties of cervical secretions, as a result of which it becomes less permeable to sperm.
When used correctly, the Pearl index (the number of pregnancies per 100 women per year) is less than 1. If you skip taking pills or use them incorrectly, the Pearl index may increase.
In women taking COCs, the menstrual cycle becomes more regular, painful menstruation is less common, and the intensity of bleeding decreases, which reduces the risk of developing anemia. In addition, according to epidemiological studies, the use of COCs reduces the risk of developing endometrial and ovarian cancer.
Drospirenone contained in Dimia® has an antimineralocorticoid effect. Prevents weight gain and the appearance of edema associated with fluid retention caused by estrogen, which ensures good tolerability of the drug. Drospirenone has a positive effect on premenstrual syndrome (PMS). The combination of drospirenone/ethinyl estradiol has been shown to be clinically effective in relieving symptoms of severe PMS, such as severe psychoemotional disturbances, breast engorgement, headache, muscle and joint pain, weight gain and other symptoms associated with the menstrual cycle. Drospirenone also has antiandrogenic activity and helps reduce the symptoms of acne (blackheads), oily skin and hair. This action of drospirenone is similar to the action of natural progesterone produced by the body.
Drospirenone does not have androgenic, estrogenic, glucocorticoid or antiglucocorticoid activity. All this, combined with antimineralocorticoid and antiandrogenic effects, provides drospirenone with a biochemical and pharmacological profile similar to natural progesterone.
When combined with ethinyl estradiol, drospirenone demonstrates a beneficial effect on the lipid profile, characterized by an increase in high-density lipoproteins.

Pharmacokinetics

Drospirenone
Suction
When taken orally, drospirenone is rapidly and almost completely absorbed from the gastrointestinal tract. The maximum concentration in blood plasma after a single oral dose is reached after approximately 1-2 hours and is about 38 ng/ml. Bioavailability 76-85%. Concomitant use with food does not affect the bioavailability of drospirenone.
Distribution
After oral administration, a biphasic decrease in the concentration of drospirenone in the blood plasma is observed, with half-lives of 1.6 ± 0.7 hours and 27.0 ± 7.5 hours, respectively. Drospirenone binds to serum albumin and does not bind to sex hormone binding globulin (SHBG) ), or with corticosteroid binding globulin. Only 3-5% of the total concentration of drospirenone in the blood plasma is present in the form of free steroids. The increase in SHBG induced by ethinyl estradiol does not affect the binding of drospirenone to plasma proteins. The average apparent volume of distribution of drospirenone is 3.7 ± 1.2 l/kg.
Metabolism
Drospirenone is actively metabolized after oral administration. Most metabolites in blood plasma are represented by acid forms of drospirenone. Drospirenone is also a substrate for oxidative metabolism catalyzed by the cytochrome P450 isoenzyme CYP3A4.
Removal
The rate of metabolic clearance of drospirenone in blood plasma is 1.5±0.2 ml/min/kg. Unmodified drospirenone is excreted only in trace amounts. Drospirenone metabolites are excreted through the intestines and kidneys in a ratio of approximately 1.2:1.4. The half-life of metabolites by the kidneys and through the intestines is about 40 hours.
Equilibrium concentration
During cyclic administration, the maximum equilibrium concentration of drospirenone in the blood plasma is achieved between the 7th and 14th day of drug administration and is approximately 70 ng/ml. Plasma concentrations of drospirenone increase approximately 2-3 times (due to accumulation), due to the relationship between the terminal half-life and the dosing interval. A further increase in the concentration of drospirenone in the blood plasma is observed between 1 and 6 cycles of administration, after which no increase in concentration is observed.
Special patient populations
Patients with renal failure
Steady-state plasma concentrations of drospirenone in women with mild renal failure (creatinine clearance (CC) 50-80 ml/min) were comparable to those in women with normal renal function (CC>80 ml/min). In women with moderate renal failure (creatinine clearance 30-50 ml/min), the plasma concentration of drospirenone was on average 37% higher than in women with normal renal function. Drospirenone treatment was well tolerated in all groups. Taking drospirenone did not have a clinically significant effect on the concentration of potassium in the blood plasma. The pharmacokinetics of drospirenone in severe renal failure have not been studied.
Patients with liver failure
Drospirenone is well tolerated in patients with mild to moderate hepatic impairment (Child-Pugh class B). Pharmacokinetics in severe hepatic impairment have not been studied.
Ethinyl estradiol
Suction
When taken orally, ethinyl estradiol is rapidly and completely absorbed. The maximum concentration in blood plasma after a single oral dose is reached after 1-2 hours and is about 88-100 pg/ml. Absolute bioavailability as a result of first-pass conjugation and first-pass metabolism is approximately 60%. Concomitant food intake reduced the bioavailability of ethinyl estradiol in approximately 25% of the patients studied, while in others such changes were not observed.
Distribution
The plasma concentration of ethinyl estradiol decreases biphasically, with a terminal phase characterized by an elimination half-life of approximately 24 hours.
Ethinyl estradiol is significantly, but nonspecifically, bound to serum albumin (approximately 98.5%) and induces an increase in plasma concentrations of SHBG. The apparent volume of distribution is about 5 l/kg.
Metabolism
Ethinyl estradiol undergoes significant first-pass metabolism in the intestine and liver. Ethinyl estradiol and its oxidized metabolites are primarily conjugated to glucuronides or sulfate. The rate of metabolic clearance of ethinyl estradiol is approximately 5 ml/min/kg.
Removal
Ethinyl estradiol is practically not excreted unchanged. Metabolites of ethinyl estradiol are excreted by the kidneys and through the intestines in a ratio of 4:6. The half-life of metabolites is about 24 hours.
Equilibrium concentration
The state of equilibrium concentration is achieved during the second half of the drug administration cycle, and the concentration of ethinyl estradiol in the blood plasma increases by approximately 1.5-2.3 times.

Preclinical safety data

Preclinical data from routine repeated dose toxicity, genotoxicity, carcinogenicity and reproductive toxicity studies do not indicate a particular risk to humans. However, it should be remembered that sex hormones can promote the growth of certain hormone-dependent tissues and tumors.

Indications for use

• Contraception.
• Contraception and treatment of moderate acne (acne vulgaris).
• Contraception and treatment of severe premenstrual syndrome (PMS).

Contraindications

Dimia® is contraindicated in the presence of any of the conditions, diseases/risk factors listed below. If any of these conditions, diseases/risk factors develop for the first time while taking it, the drug should be discontinued immediately:

• thrombosis (venous and arterial) and thromboembolism currently or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction), cerebrovascular disorders;
• conditions preceding thrombosis (including transient ischemic attacks, angina), currently or in history;
• identified acquired or hereditary predisposition to venous or arterial thrombosis, including resistance to activated protein C, antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia, antibodies to phospholipids (anticardiolipin antibodies, lupus anticoagulant);
• presence of a high risk of venous or arterial thrombosis (see section “Special instructions”);
• migraine with focal neurological symptoms currently or in history;
• diabetes mellitus with vascular complications;
• liver failure and severe liver diseases (until normalization of liver function indicators);
• liver tumors (benign or malignant) currently or in history;
• severe renal failure, acute renal failure;
• adrenal insufficiency;
• identified hormone-dependent malignant diseases (including genital organs or mammary glands) or suspicion of them;
• bleeding from the vagina of unknown origin;
• pregnancy or suspicion of it;
• breastfeeding period;
• hypersensitivity to any of the components of the drug Dimia®;
• lactose intolerance, lactase deficiency, glucose-galactose malabsorption (the drug contains lactose monohydrate);
• hypersensitivity to peanuts or soy.

Carefully

If any of the conditions, diseases/risk factors listed below currently exist, the potential risks and expected benefits of using COCs should be carefully weighed in each individual case:

• risk factors for the development of thrombosis and thromboembolism: smoking; thrombosis, myocardial infarction or cerebrovascular accident under the age of 50 in one of the immediate family; overweight (body mass index (BMI) less than 30 kg/m2); dyslipoproteinemia; controlled arterial hypertension; migraine; uncomplicated heart valve diseases; heart rhythm disturbance;
• other diseases in which peripheral circulatory disorders may occur: diabetes mellitus; systemic lupus erythematosus; hemolytic-uremic syndrome; Crohn's disease and ulcerative colitis; sickle cell anemia; as well as phlebitis of superficial veins;
• hereditary angioedema;
• hypertriglyceridemia;
• liver diseases;
• diseases that first appeared or worsened during pregnancy or against the background of previous use of sex hormones (for example, jaundice, cholestasis, cholelithiasis, otosclerosis with hearing impairment, porphyria, herpes of pregnant women, Sydenham's chorea);
• postpartum period.

Use during pregnancy and breastfeeding

Pregnancy
Dimia® is contraindicated during pregnancy. If the patient is planning a pregnancy, she can stop taking Dimia® at any time. If pregnancy is detected while using Dimia®, its use should be stopped immediately. However, extensive epidemiological studies have not shown any increased risk of developmental defects in children born to women who received sex hormones (including COCs) before pregnancy, or teratogenic effects when sex hormones were taken inadvertently in early pregnancy.
Existing data on the results of taking Dimia® during pregnancy are limited, which does not allow us to draw any conclusions about the effect of the drug on the course of pregnancy, the health of the newborn and the fetus. There are currently no significant epidemiological data on Dimia®.
Breastfeeding period
The use of Dimia® during breastfeeding is contraindicated. Taking COCs can reduce the amount of breast milk and change its composition, so their use is not recommended until breastfeeding is stopped. Small amounts of sex hormones and/or their metabolites can pass into breast milk and affect the newborn's body.

Directions for use and dosage

Directions for use: for oral administration.
How to take Dimia®
The tablets should be taken daily, at approximately the same time, with a small amount of water, in the order indicated on the blister pack. The tablets are taken continuously for 28 days, 1 tablet per day. Taking tablets from each subsequent package should begin the day after taking the last tablet from the previous package. Withdrawal bleeding usually begins 2-3 days after you start taking the green placebo pills (last row) and may not end before you start taking the next pack of pills. You should always start taking pills from a new pack on the same day of the week, and withdrawal bleeding will occur on approximately the same days each month.
How to start taking Dimia®

• If you have not taken any hormonal contraceptives in the previous month
  Taking Dimia® should be started on the first day of the menstrual cycle (i.e., on the first day of menstrual bleeding), in which case additional contraceptive measures are not required. It is possible to start taking it on days 2-5 of the menstrual cycle, but in this case it is recommended to additionally use a barrier method of contraception during the first 7 days of taking the tablets from the first package.
• When switching from other combined contraceptives (COCs, vaginal ring or transdermal patch)
  It is preferable to start taking Dimia® the next day after taking the last inactive tablet (for preparations containing 28 tablets per package) or the next day after taking the last active tablet from the previous package, but in no case later than the next day after the usual 7- daily break (for drugs containing 21 tablets). Taking Dimia® should be started on the day the vaginal ring or patch is removed, but no later than the day when a new ring is to be inserted or a new patch is applied.
• When switching from contraceptives containing only gestagens (mini-pills, injection forms, implant), or from a gestagen-releasing intrauterine contraceptive
  A woman can switch from the “mini-pill” to Dimia® any day (without a break); from an implant or intrauterine contraceptive with gestagen - on the day of its removal, from an injectable contraceptive - on the day when the next injection is due. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills.
• After an abortion in the first trimester of pregnancy
  A woman can start taking the drug immediately after a spontaneous or medical abortion in the first trimester of pregnancy. If this condition is met, the woman does not need additional contraceptive measures.
• After an abortion in the second trimester of pregnancy or childbirth
  Taking the drug can be started 21-28 days after a spontaneous or medical abortion or after childbirth, in the absence of breastfeeding. If use is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills. However, if sexual contact has already taken place, pregnancy should be excluded before starting to take Dimia® or you must wait until your first menstruation.

Stopping taking Dimia®

You can stop taking the drug at any time. If a woman is not planning a pregnancy, or if a woman is contraindicated for pregnancy because she is taking medications that are potentially harmful to the fetus, other methods of contraception should be discussed with the doctor.
If a woman is planning a pregnancy, it is recommended to stop taking the drug and wait for natural menstrual bleeding before trying to become pregnant. This will help you more accurately calculate your gestational age and delivery time.

Taking missed pills

Skipping a placebo tablet from the last (4th) row of the blister can be ignored.
However, they should be discarded to avoid inadvertently prolonging the placebo phase. The following recommendations apply only to skipping active tablets. If the delay in taking the drug was

Less than 24 hours

Contraceptive protection is not reduced. The woman should take the missed pill as soon as possible and take the next pill at the usual time.
If you are late in taking your pills

More than 24 hours

Contraceptive protection may be reduced. The more pills you skip, and the closer the missed pills are to the inactive green placebo pill phase, the higher the chance of pregnancy.
In this case, you can be guided by the following two basic rules:

1. The drug should never be interrupted for more than 7 days;
2. To achieve adequate suppression of the hypothalamic-pituitary-ovarian axis, 7 days of continuous tablet use are required.

In accordance with this, a woman can be given the following recommendations:

• If you miss pills from days 1 to 7:
  A woman should take the last missed pill as soon as she remembers, even if this means taking two pills at the same time. She continues to take her next pills at the usual time. In addition, over the next 7 days it is necessary to additionally use a barrier method of contraception (for example, a condom). If sexual intercourse took place within 7 days before missing a pill, the possibility of pregnancy should be taken into account.
• If you miss pills between days 8 and 14:
  A woman should take the last missed pill as soon as she remembers, even if this means taking two pills at the same time. She continues to take her next pills at the usual time. If a woman has taken her pills correctly in the 7 days preceding the first missed pill, there is no need for additional contraceptive measures. Otherwise, as well as if you miss two or more tablets, you must additionally use barrier methods of contraception (for example, a condom) for 7 days.
• If you miss pills between days 15 and 24:
  The risk of reduced reliability is imminent due to the approaching period of taking the inactive green placebo pills. You must strictly adhere to one of the following two options. However, if during the 7 days preceding the first missed pill, all pills were taken correctly, there is no need to use additional contraceptive methods. Otherwise, the woman must use the first of the following regimens and additionally use a barrier method of contraception (for example, a condom) for 7 days.

1. A woman should take the last missed tablet as soon as she remembers, even if this means taking two tablets at the same time. The next tablets are taken at the usual time until the active tablets in the pack are gone, the 4 green placebo tablets from the last row should be discarded and the tablets from the next pack should be started immediately.
   Withdrawal bleeding is unlikely until the second pack of tablets is gone, but spotting and/or breakthrough bleeding may occur while taking the tablets.
2. A woman can also stop taking active tablets from the current package. She should then take the green placebo pills from the last row for 4 days, including the days she missed pills, and then start taking the pills from the new pack.
   If a woman misses taking active pills and does not experience withdrawal bleeding while taking inactive green placebo pills, pregnancy must be ruled out.

Recommendations for gastrointestinal disorders

In case of severe gastrointestinal disorders, absorption may be incomplete, so additional contraceptive measures should be taken. If you have vomiting or diarrhea within 3-4 hours after taking an active tablet, you should follow the recommendations for skipping tablets. If a woman does not want to change her usual dosing regimen and postpone the onset of menstruation to another day of the week, she should take an additional active tablet.

How to change/delay the onset of withdrawal bleeding

To delay the onset of withdrawal bleeding, a woman should continue taking tablets from the next package of Dimia®, skipping the inactive green tablets from the current package. Thus, the cycle can be extended at will for any period until the active tablets from the second package run out, that is, about 3 weeks later than usual.
If you plan to start your next cycle earlier, you must stop taking the active tablets from the second pack at any time, throw away the remaining active tablets and start taking the inactive green tablets (for a maximum of 4 days), and then start taking the tablets from the new pack. In this case, approximately 2-3 days after taking the last active tablet from the previous package, withdrawal bleeding should begin. While taking the drug from the second package, a woman may experience spotting and/or breakthrough uterine bleeding. Regular use of Dimia® is then resumed after the period of taking the inactive green tablets has ended.
To postpone the onset of withdrawal bleeding to another day of the week, a woman should reduce her next period of taking the inactive green pills by the desired number of days. The shorter the interval, the higher the risk that she will not have withdrawal bleeding and will subsequently experience spotting and/or breakthrough bleeding while taking the pills from the second package.

Use in special categories of patients

Children and teenagers
Dimia® is indicated only after menarche. Available data do not suggest dose adjustment in this group of patients.
Elderly patients
Dimia® is not indicated after menopause.
Patients with liver dysfunction
Dimia® is contraindicated in women with severe liver disease until liver function tests return to normal (see also sections “Contraindications” and “Pharmacological properties”).
Patients with impaired renal function
Dimia® is contraindicated in women with severe renal failure or acute renal failure (see also sections “Contraindications” and “Pharmacological properties”).

Side effect

The following adverse drug reactions (ADRs) were observed during use of the drospirenone/ethinyl estradiol combination.
ADRs are presented according to systemic organ classes in accordance with the MedDRA classification and with the frequency of occurrence: often (>1/100 and<1/10), нечасто (>1/1000 and<1/100) и редко (>1/10,000 and<1/1000). В пределах каждой группы, выделенной в зависимости от частоты возникновения, НЛР представлены в порядке уменьшения их тяжести. Для дополнительных нежелательных реакций, выявленных только в процессе пострегистрационных наблюдений, и для которых оценку частоты возникновения провести не представлялось возможным, указано «частота неизвестна».

Open side effects table in a new window

* the frequency of irregular bleeding decreases as the duration of taking Dimia® increases.

Additional Information
Listed below are adverse reactions with a very rare incidence or with delayed symptoms, which are believed to be associated with the use of drugs from the COC group (see also sections “Contraindications” and “Special instructions”).
Tumors

• The incidence of breast cancer diagnosis in women taking COCs is slightly increased. Due to the fact that breast cancer is rare in women under 40 years of age, the increase in breast cancer diagnoses in women taking COCs is small relative to the overall risk of this disease.
• Liver tumors (benign and malignant).

Other states

• women with hypertriglyceridemia have an increased risk of pancreatitis while taking COCs;
• increased blood pressure;
• conditions that develop or worsen while taking COCs, but their relationship has not been proven: jaundice and/or itching associated with cholestasis; cholelithiasis; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; chorea; herpes during pregnancy; hearing loss associated with otosclerosis;
• in women with hereditary angioedema, taking estrogens may cause or aggravate its symptoms;
• liver dysfunction;
• changes in glucose tolerance or effects on insulin resistance;
• Crohn's disease, ulcerative colitis;
• chloasma;
• hypersensitivity (including symptoms such as rash, urticaria).

Interaction
Interaction of COCs with other drugs (enzyme inducers) may lead to breakthrough bleeding and/or decreased contraceptive effectiveness (see section “Interaction with other drugs”).
If any of the side effects indicated in the instructions get worse or you notice any other side effects not listed in the instructions, tell your doctor.

Overdose

No serious adverse events have been reported following overdose. In preclinical studies, there were also no serious adverse effects resulting from overdose.
Symptoms which may occur in case of overdose: nausea, vomiting, spotting vaginal discharge or metrorrhagia.
Treatment. There is no specific antidote; symptomatic treatment should be carried out.

Interaction with other drugs Effect of other drugs on Dimia®

It is possible to interact with drugs that induce microsomal enzymes, which may result in an increase in the clearance of sex hormones, which, in turn, can lead to breakthrough uterine bleeding and/or a decrease in the contraceptive effect. Women who are treated with such drugs in addition to Dimia® are recommended to use a barrier method of contraception or choose another non-hormonal method of contraception (if long-term use of inducer drugs is necessary).
A barrier method of contraception should be used during the entire period of taking concomitant medications, as well as for 28 days after their discontinuation. If the use of drugs that induce microsomal liver enzymes continues after the end of the active tablets in the Dimia® package, you should start taking Dimia® tablets from the new package without taking green placebo tablets from the old package.

• Substances that increase the clearance of Dimia®(impairing effectiveness by enzyme induction): phenytoin, barbiturates, primidone, carbamazepine, rifampicin and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin, as well as preparations containing St. John's wort.
• Substances with different effects on the clearance of Dimia®
  When used together with Dimia®, many HIV or hepatitis C virus protease inhibitors and non-nucleoside reverse transcriptase inhibitors can both increase and decrease the concentration of estrogens or progestogens in the blood plasma. In some cases, this effect may be clinically significant.
• Substances that reduce the clearance of COCs (enzyme inhibitors)
  Strong and moderate inhibitors of CYP3A4, such as azole antimycotics (eg, itraconazole, voriconazole, fluconazole), verapamil, macrolides (eg, clarithromycin, erythromycin), diltiazem and grapefruit juice may increase plasma concentrations of estrogen or progestogen, or both. Etoricoxib at doses of 60 and 120 mg/day, when coadministered with COCs containing 0.035 mg ethinyl estradiol, has been shown to increase plasma ethinyl estradiol concentrations by 1.4 and 1.6 times, respectively.

Effect of Dimia® on other drugs

COCs may affect the metabolism of other drugs, leading to an increase (for example, cyclosporine) or a decrease (for example, lamotrigine) in their plasma and tissue concentrations.
In vitro, drospirenone is capable of weakly or moderately inhibiting cytochrome P450 isoenzymes CYP1A1, CYP2C9, CYP2C19 and CYP3A4.
Based on in vivo interaction studies in female volunteers taking omeprazole, simvastatin or midazolam as marker substrates, it can be concluded that a clinically significant effect of 3 mg drospirenone on cytochrome P450-mediated drug metabolism is unlikely.
In vitro, ethinyl estradiol is a reversible inhibitor of the isoenzymes CYP2C19, CYP1A1 and CYP1A2, as well as an irreversible inhibitor of the isoenzymes CYP3A4/5, CYP2C8 and CYP2J2. In clinical studies, administration of a hormonal contraceptive containing ethinyl estradiol did not result in any increase or only a slight increase in plasma concentrations of CYP3A4 substrates (eg, midazolam), while plasma concentrations of CYP1A2 substrates may increase slightly (eg, theophylline) or moderate (eg, melatonin and tizanidine).

Other forms of interaction

In patients with preserved renal function, the combined use of drospirenone and angiotensin-converting enzyme inhibitors or non-steroidal anti-inflammatory drugs does not have a significant effect on the concentration of potassium in the blood plasma. However, the combined use of Dimia® with aldosterone antagonists or potassium-sparing diuretics has not been studied. In such cases, the concentration of potassium in the blood plasma must be monitored during the first cycle of taking the drug (see section "Special instructions").

special instructions

If any of the conditions, diseases/risk factors listed below currently exist, the potential risks and expected benefits of using COCs should be carefully weighed in each individual case and discussed with the woman before she decides to start taking the drug. If any of these conditions, diseases or risk factors worsen, intensify, or appear for the first time, a woman should consult her doctor, who may decide whether to discontinue the drug.
Diseases of the cardiovascular system
The results of epidemiological studies indicate a relationship between the use of COCs and an increased incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders). These diseases are rare.
The risk of developing venous thromboembolism (VTE) is greatest in the first year of using such drugs. An increased risk is present after initial use of COCs or resumption of use of the same or different COCs (after a dosing interval of 4 weeks or more). Data from a prospective study involving 3 groups of patients indicate that this increased risk is predominantly present during the first 3 months of drug use. The overall risk of VTE in patients taking low-dose COCs (<0,05 мг этинилэстрадиола) в 2-3 раза выше, чем у небеременных пациенток, которые не принимают КОК, тем не менее, этот риск остается более низким по сравнению с риском ВТЭ при беременности и родах. ВТЭ может угрожать жизни или привести к летальному исходу (в 1-2% случаев).
VTE, manifested as deep vein thrombosis or pulmonary embolism, can occur with the use of any COC.
It is extremely rare when using COCs that thrombosis of other blood vessels occurs, for example, hepatic, mesenteric, renal, cerebral veins and arteries or retinal vessels. There is no consensus regarding the relationship between the occurrence of these diseases and the use of COCs.
Symptoms of deep vein thrombosis (DVT) include the following: unilateral swelling of the lower extremity or along a vein in the lower extremity, pain or discomfort in the lower extremity only when standing or walking, localized warmth in the affected lower extremity, redness or discoloration of the skin on lower limb.
Symptoms of pulmonary embolism (PE) include: difficulty or rapid breathing; sudden cough, including with hemoptysis; sharp pain in the chest, which may intensify with deep inspiration; sense of anxiety; severe dizziness; fast or irregular heartbeat. Some of these symptoms (eg, shortness of breath, cough) are nonspecific and may be misinterpreted as signs of other more or less severe conditions (eg, respiratory tract infection).
Arterial thromboembolism can lead to stroke, vascular occlusion, or myocardial infarction.
Symptoms of a stroke include: sudden weakness or loss of sensation in the face, limbs, especially on one side of the body, sudden confusion, problems with speech and comprehension; sudden unilateral or bilateral vision loss; sudden disturbance in gait, dizziness, loss of balance or coordination; sudden, severe or prolonged headache for no apparent reason; loss of consciousness or fainting with or without an epileptic seizure.
Other signs of vascular occlusion: sudden pain, swelling and slight blue discoloration of the limbs, “acute” abdomen.
Symptoms of a myocardial infarction include: pain, discomfort, a feeling of pressure, heaviness, squeezing, or fullness in the chest, arm, or chest; discomfort radiating to the back, cheekbone, larynx, arm, stomach; cold sweat, nausea, vomiting or dizziness, severe weakness, anxiety or shortness of breath; fast or irregular heartbeat.
Arterial thromboembolism can be life-threatening or fatal. In women with a combination of several risk factors or high severity of one of them, the possibility of their mutual reinforcement should be considered. In such cases, the degree of increase in risk may be higher than with a simple summation of factors. In this case, taking Dimia® is contraindicated (see section “Contraindications”).
The risk of developing thrombosis (venous and/or arterial) and thromboembolism increases:

• with age;
• in smokers (with increasing number of cigarettes or increasing age, the risk increases, especially in women over 35 years of age);

in the presence of:

• obesity (BMI more than 30 kg/m2);
• family history (for example, venous or arterial thromboembolism ever in close relatives or parents under the age of 50 years). In the case of a hereditary or acquired predisposition, the woman should be examined by an appropriate specialist to decide on the possibility of taking COCs;
• prolonged immobilization, major surgery, any operation on the lower limb or major trauma. In these cases, the use of Dimia® should be discontinued. In case of planned surgery, the drug should be stopped at least 4 weeks before the operation and should not be resumed for two weeks after complete restoration of motor activity. Temporary immobilization (eg, air travel lasting more than 4 hours) may also be a risk factor for the development of venous thromboembolism, especially in the presence of other risk factors;
• dyslipoproteinemia;
• arterial hypertension;
• migraine;
• heart valve diseases;
• atrial fibrillation.

The use of any combined hormonal contraceptives increases the risk of developing VTE. The use of drugs containing levonorgestrel, norgestimate or norethisterone is associated with the lowest risk of developing VTE. The use of other drugs, such as Dimia®, may double the risk. The decision to use a drug other than the one with the lowest risk of developing VTE should be made only after discussion with the woman to ensure that she understands that the use of Dimia® is accompanied by the likelihood of developing VTE, and understands how her existing risk factors affect the likelihood of developing VTE, and also understands that in each first year of using the drug, her risk of developing VTE is greatest.
The possible role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism remains controversial.
The increased risk of thromboembolism in the postpartum period should be taken into account. Peripheral circulatory disorders may also occur in diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell anemia.
An increase in the frequency and severity of migraine during the use of COCs (which may precede cerebrovascular events) is grounds for immediate discontinuation of these drugs.
Biochemical indicators indicating a hereditary or acquired predisposition to venous or arterial thrombosis include the following: resistance to activated protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).
When assessing the risk-benefit ratio, it should be taken into account that adequate treatment of the relevant condition can reduce the associated risk of thrombosis. It should also be taken into account that the risk of thrombosis and thromboembolism during pregnancy is higher than when taking low-dose COCs (<0,05 мг этинилэстрадиола).
Tumors
The most significant risk factor for developing cervical cancer is persistent human papillomavirus infection. There are reports of a slight increase in the risk of developing cervical cancer with long-term use of COCs, but the relationship with COC use has not been proven. Controversy remains regarding the extent to which these findings are related to screening for cervical pathology or to sexual behavior (lower use of barrier methods of contraception).
A meta-analysis of 54 epidemiological studies showed that there is a slightly increased relative risk of developing breast cancer diagnosed in women currently taking COCs (relative risk 1.24). The increased risk gradually disappears within 10 years of stopping these drugs. Because breast cancer is rare in women under 40 years of age, the increase in breast cancer diagnoses in current or recent COC users is small relative to the overall risk of breast cancer. The observed increased risk may be due to earlier diagnosis of breast cancer in women using COCs, their biological effects, or a combination of both factors. Women who have used COCs are diagnosed with earlier stages of breast cancer than women who have never used them.
In rare cases, during the use of COCs, the development of benign, and in extremely rare cases, malignant liver tumors, which in some cases led to life-threatening intra-abdominal bleeding, was observed. These conditions should be taken into account when making a differential diagnosis in the event of severe abdominal pain, liver enlargement, or signs of intra-abdominal bleeding.
Tumors can be life-threatening or fatal.
Other states
Clinical studies have shown no effect of drospirenone on plasma potassium concentrations in patients with mild to moderate renal failure. There is a theoretical risk of developing hyperkalemia in patients with impaired renal function with an initial potassium concentration at the upper limit of normal, while simultaneously taking medications that lead to potassium retention in the body. In women with an increased risk of developing hyperkalemia, it is recommended to determine the concentration of potassium in the blood plasma during the first cycle of taking Dimia®.
Women with hypertriglyceridemia (or a family history of this condition) may have an increased risk of developing pancreatitis while taking COCs.
Although slight increases in blood pressure have been described in many women taking COCs, clinically significant increases have rarely been reported. However, if a persistent clinically significant increase in blood pressure develops while taking COCs, these drugs should be discontinued and treatment of arterial hypertension should be initiated. COC use can be continued if normal blood pressure values ​​are achieved with antihypertensive therapy.
The following conditions have been reported to develop or worsen both during pregnancy and while taking COCs, but their relationship with COC use has not been proven: jaundice and/or pruritus associated with cholestasis; cholelithiasis; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; chorea; herpes during pregnancy; hearing loss associated with otosclerosis. Cases of worsening the course of endogenous depression, epilepsy, Crohn's disease and ulcerative colitis during the use of COCs have also been described.
In women with hereditary forms of angioedema, exogenous estrogens may cause or worsen symptoms of angioedema.
Acute or chronic liver dysfunction may require discontinuation of COCs until liver function tests return to normal. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous use of sex hormones, requires discontinuation of COC use.
Although COCs may have an effect on insulin resistance and glucose tolerance, there is no need to change the dose of hypoglycemic drugs in diabetic patients using low-dose COCs (<0,05 мг этинил-эстрадиола). Тем не менее, женщины с сахарным диабетом должны тщательно наблюдаться во время приема КОК.
Chloasma can sometimes develop, especially in women with a history of chloasma during pregnancy. Women with a tendency to chloasma should avoid prolonged exposure to the sun and exposure to ultraviolet radiation while taking COCs.
Laboratory tests
Taking COCs may affect the results of some laboratory tests, including indicators of liver, kidney, thyroid, adrenal function, the concentration of transport proteins in the blood plasma, indicators of carbohydrate metabolism, parameters of coagulation and fibrinolysis. Changes usually do not go beyond normal values. Drospirenone increases the activity of plasma renin and aldosterone, which is associated with its antimineralocorticoid effect.
Medical examinations
Before starting or resuming taking the drug Dimia®, it is necessary to familiarize yourself with the woman’s life history, family history, conduct a thorough medical (including measurement of blood pressure, heart rate, determination of BMI) and gynecological examination (including examination of the mammary glands and cytological examination of scrapings from the cervix), exclude pregnancy. The scope of additional studies and the frequency of follow-up examinations are determined individually. Typically, follow-up examinations should be carried out at least once every 6 months.
The woman should be warned that COCs do not protect against HIV infection (AIDS) and other sexually transmitted diseases.
Reduced efficiency
The effectiveness of COCs may be reduced in the following cases: if active tablets are missed, with vomiting and diarrhea, or as a result of drug interactions.
Poor control of the menstrual cycle
While taking COCs, irregular bleeding may occur (“spotting” and/or “breakthrough” bleeding), especially during the first months of use. Therefore, any irregular bleeding should be assessed only after an adaptation period of approximately three cycles.
If irregular bleeding recurs or develops after previous regular cycles, a thorough diagnostic evaluation should be performed to rule out malignancy or pregnancy.
Some women may not experience withdrawal bleeding while taking green, inactive placebo pills. If the drug is taken as directed, it is unlikely that the woman is pregnant. However, if the drug has not been taken regularly before, or if there are no two withdrawal bleedings in a row, pregnancy should be ruled out before continuing to take the drug.
Lactose
Dimia®, film-coated tablets, contains lactose. Patients with rare hereditary diseases such as galactose intolerance, lactase deficiency and glucose-galactose malabsorption should not take this drug.
Soybeans
Dimia®, film-coated tablets, contains soy lecithin. Patients with peanut and soy allergies should not take this drug.

Catad_pgroup Combined oral contraceptives

The most physiological contraceptive that preserves the quality of sexual life. For the treatment of heavy and/or prolonged menstrual bleeding without organic pathology.
INFORMATION IS PROVIDED STRICTLY
FOR HEALTH PROFESSIONALS

Dimia - official instructions for use

Registration number:

LP-001179

Trade name of the drug:

Dimia®

International nonproprietary name:

drospirenone + ethinylestradiol

Dosage form:

film-coated tablets [set]

Compound:

for 1 tablet:
Drospirenone + ethinyl estradiol tablets
active substance: drospirenone 3.000 mg, ethinyl estradiol 0.020 mg;
Excipients: lactose monohydrate, corn starch, pregelatinized corn starch, macrogol and polyvinyl alcohol copolymer, magnesium stearate.
Film casing (Opadray II white*): polyvinyl alcohol, titanium dioxide, macrogol-3350, talc, soy lecithin.
*code 85G18490
Placebo tablets
microcrystalline cellulose, lactose, pregelatinized corn starch, magnesium stearate, colloidal silicon dioxide.
Film casing (Opadray II green**): polyvinyl alcohol, titanium dioxide, macrogol-3350, talc, indigo carmine, quinoline yellow dye, black iron oxide dye; sunset yellow dye.
** code 85F21389

Description:

For drospirenone + ethinyl estradiol tablets:
Round, biconvex, white or off-white film-coated tablets, embossed with "G73" on one side of the tablet. On a cross section, the core is white or almost white.
For placebo tablets:
Round, biconvex tablets, green film-coated. On a cross section, the core is white or almost white.

Pharmacotherapeutic group:

combined contraceptive (estrogen + gestagen)

ATX code:

G03AA12

Pharmacological properties

Pharmacodynamics
The drug Dimia® is a combined hormonal contraceptive with antimineralocorticoid and antiandrogenic effects. The contraceptive effect of combined oral contraceptive drugs (COCs) is based on the interaction of various factors, the most important of which are suppression of ovulation and changes in the properties of cervical secretions, as a result of which it becomes less permeable to sperm.
When used correctly, the Pearl index (the number of pregnancies per 100 women per year) is less than 1. If you skip taking pills or use them incorrectly, the Pearl index may increase.
In women taking COCs, the menstrual cycle becomes more regular, painful menstruation is less common, and the intensity of bleeding decreases, which reduces the risk of developing anemia. In addition, according to epidemiological studies, the use of COCs reduces the risk of developing endometrial and ovarian cancer.
Drospirenone contained in Dimia® has an antimineralocorticoid effect. Prevents weight gain and the appearance of edema associated with fluid retention caused by estrogen, which ensures good tolerability of the drug. Drospirenone has a positive effect on premenstrual syndrome (PMS). The combination of drospirenone/ethinyl estradiol has been shown to be clinically effective in relieving symptoms of severe PMS, such as severe psychoemotional disturbances, breast engorgement, headache, muscle and joint pain, weight gain and other symptoms associated with the menstrual cycle. Drospirenone also has antiandrogenic activity and helps reduce the symptoms of acne (blackheads), oily skin and hair. This action of drospirenone is similar to the action of natural progesterone produced by the body.
Drospirenone does not have androgenic, estrogenic, glucocorticoid or antiglucocorticoid activity. All this, combined with antimineralocorticoid and antiandrogenic effects, provides drospirenone with a biochemical and pharmacological profile similar to natural progesterone.
When combined with ethinyl estradiol, drospirenone demonstrates a beneficial effect on the lipid profile, characterized by an increase in high-density lipoproteins.

Pharmacokinetics
Drospirenone
Suction
When taken orally, drospirenone is rapidly and almost completely absorbed from the gastrointestinal tract. The maximum concentration in blood plasma after a single oral dose is reached after approximately 1-2 hours and is about 38 ng/ml. Bioavailability 76-85%. Concomitant use with food does not affect the bioavailability of drospirenone.
Distribution
After oral administration, a biphasic decrease in the concentration of drospirenone in the blood plasma is observed, with half-lives of 1.6 ± 0.7 hours and 27.0 ± 7.5 hours, respectively. Drospirenone binds to serum albumin and does not bind to sex hormone binding globulin (SHBG) ), or with corticosteroid binding globulin. Only 3-5% of the total concentration of drospirenone in the blood plasma is present in the form of free steroids. The increase in SHBG induced by ethinyl estradiol does not affect the binding of drospirenone to plasma proteins. The average apparent volume of distribution of drospirenone is 3.7 ± 1.2 l/kg.
Metabolism
Drospirenone is actively metabolized after oral administration. Most metabolites in blood plasma are represented by acid forms of drospirenone. Drospirenone is also a substrate for oxidative metabolism catalyzed by the cytochrome P450 isoenzyme CYP3A4.
Removal
The rate of metabolic clearance of drospirenone in blood plasma is 1.5±0.2 ml/min/kg. Unmodified drospirenone is excreted only in trace amounts. Drospirenone metabolites are excreted through the intestines and kidneys in a ratio of approximately 1.2:1.4. The half-life of metabolites by the kidneys and through the intestines is about 40 hours.
Equilibrium concentration
During cyclic administration, the maximum equilibrium concentration of drospirenone in the blood plasma is achieved between the 7th and 14th day of drug administration and is approximately 70 ng/ml. Plasma concentrations of drospirenone increase approximately 2-3 times (due to accumulation), due to the relationship between the terminal half-life and the dosing interval. A further increase in the concentration of drospirenone in the blood plasma is observed between 1 and 6 cycles of administration, after which no increase in concentration is observed.
Special patient populations
Patients with renal failure
Steady-state plasma concentrations of drospirenone in women with mild renal failure (creatinine clearance (CC) 50-80 ml/min) were comparable to those in women with normal renal function (CC>80 ml/min). In women with moderate renal failure (creatinine clearance 30-50 ml/min), the plasma concentration of drospirenone was on average 37% higher than in women with normal renal function. Drospirenone treatment was well tolerated in all groups. Taking drospirenone did not have a clinically significant effect on the concentration of potassium in the blood plasma. The pharmacokinetics of drospirenone in severe renal failure have not been studied.
Patients with liver failure
Drospirenone is well tolerated in patients with mild to moderate hepatic impairment (Child-Pugh class B). Pharmacokinetics in severe hepatic impairment have not been studied.
Ethinyl estradiol
Suction
When taken orally, ethinyl estradiol is rapidly and completely absorbed. The maximum concentration in blood plasma after a single oral dose is reached after 1-2 hours and is about 88-100 pg/ml. Absolute bioavailability as a result of first-pass conjugation and first-pass metabolism is approximately 60%. Concomitant food intake reduced the bioavailability of ethinyl estradiol in approximately 25% of the patients studied, while in others such changes were not observed.
Distribution
The plasma concentration of ethinyl estradiol decreases biphasically, with a terminal phase characterized by an elimination half-life of approximately 24 hours.
Ethinyl estradiol is significantly, but nonspecifically, bound to serum albumin (approximately 98.5%) and induces an increase in plasma concentrations of SHBG. The apparent volume of distribution is about 5 l/kg.
Metabolism
Ethinyl estradiol undergoes significant first-pass metabolism in the intestine and liver. Ethinyl estradiol and its oxidized metabolites are primarily conjugated to glucuronides or sulfate. The rate of metabolic clearance of ethinyl estradiol is approximately 5 ml/min/kg.
Removal
Ethinyl estradiol is practically not excreted unchanged. Metabolites of ethinyl estradiol are excreted by the kidneys and through the intestines in a ratio of 4:6. The half-life of metabolites is about 24 hours.
Equilibrium concentration
The state of equilibrium concentration is achieved during the second half of the drug administration cycle, and the concentration of ethinyl estradiol in the blood plasma increases by approximately 1.5-2.3 times.
Preclinical safety data
Preclinical data from routine repeated dose toxicity, genotoxicity, carcinogenicity and reproductive toxicity studies do not indicate a particular risk to humans. However, it should be remembered that sex hormones can promote the growth of certain hormone-dependent tissues and tumors.

Indications for use

• Contraception.
• Contraception and treatment of moderate acne (acne vulgaris).
• Contraception and treatment of severe premenstrual syndrome (PMS).

Contraindications

Dimia® is contraindicated in the presence of any of the conditions, diseases/risk factors listed below. If any of these conditions, diseases/risk factors develop for the first time while taking it, the drug should be discontinued immediately:

• thrombosis (venous and arterial) and thromboembolism currently or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction), cerebrovascular disorders;
• conditions preceding thrombosis (including transient ischemic attacks, angina), currently or in history;
• identified acquired or hereditary predisposition to venous or arterial thrombosis, including resistance to activated protein C, antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia, antibodies to phospholipids (anticardiolipin antibodies, lupus anticoagulant);
• presence of a high risk of venous or arterial thrombosis (see section “Special instructions”);
• migraine with focal neurological symptoms currently or in history;
• diabetes mellitus with vascular complications;
• liver failure and severe liver diseases (until normalization of liver function indicators);
• liver tumors (benign or malignant) currently or in history;
• severe renal failure, acute renal failure;
• adrenal insufficiency;
• identified hormone-dependent malignant diseases (including genital organs or mammary glands) or suspicion of them;
• bleeding from the vagina of unknown origin;
• pregnancy or suspicion of it;
• breastfeeding period;
• hypersensitivity to any of the components of the drug Dimia®;
• lactose intolerance, lactase deficiency, glucose-galactose malabsorption (the drug contains lactose monohydrate);
• hypersensitivity to peanuts or soy.

Carefully

If any of the conditions, diseases/risk factors listed below currently exist, the potential risks and expected benefits of using COCs should be carefully weighed in each individual case:

• risk factors for the development of thrombosis and thromboembolism: smoking; thrombosis, myocardial infarction or cerebrovascular accident under the age of 50 in one of the immediate family; overweight (body mass index (BMI) less than 30 kg/m2); dyslipoproteinemia; controlled arterial hypertension; migraine; uncomplicated heart valve diseases; heart rhythm disturbance;
• other diseases in which peripheral circulatory disorders may occur: diabetes mellitus; systemic lupus erythematosus; hemolytic-uremic syndrome; Crohn's disease and ulcerative colitis; sickle cell anemia; as well as phlebitis of superficial veins;
• hereditary angioedema;
• hypertriglyceridemia;
• liver diseases;
• diseases that first appeared or worsened during pregnancy or against the background of previous use of sex hormones (for example, jaundice, cholestasis, cholelithiasis, otosclerosis with hearing impairment, porphyria, herpes of pregnant women, Sydenham's chorea);
• postpartum period.

Use during pregnancy and breastfeeding

Pregnancy
Dimia® is contraindicated during pregnancy. If the patient is planning a pregnancy, she can stop taking Dimia® at any time. If pregnancy is detected while using Dimia®, its use should be stopped immediately. However, extensive epidemiological studies have not shown any increased risk of developmental defects in children born to women who received sex hormones (including COCs) before pregnancy, or teratogenic effects when sex hormones were taken inadvertently in early pregnancy.
Existing data on the results of taking Dimia® during pregnancy are limited, which does not allow us to draw any conclusions about the effect of the drug on the course of pregnancy, the health of the newborn and the fetus. There are currently no significant epidemiological data on Dimia®.
Breastfeeding period
The use of Dimia® during breastfeeding is contraindicated. Taking COCs can reduce the amount of breast milk and change its composition, so their use is not recommended until breastfeeding is stopped. Small amounts of sex hormones and/or their metabolites can pass into breast milk and affect the newborn's body.

Directions for use and doses

Directions for use: for oral administration.
How to take Dimia®
The tablets should be taken daily, at approximately the same time, with a small amount of water, in the order indicated on the blister pack. The tablets are taken continuously for 28 days, 1 tablet per day. Taking tablets from each subsequent package should begin the day after taking the last tablet from the previous package. Withdrawal bleeding usually begins 2-3 days after you start taking the green placebo pills (last row) and may not end before you start taking the next pack of pills. You should always start taking pills from a new pack on the same day of the week, and withdrawal bleeding will occur on approximately the same days each month.
How to start taking Dimia®

• If you have not taken any hormonal contraceptives in the previous month
  Taking Dimia® should be started on the first day of the menstrual cycle (i.e., on the first day of menstrual bleeding), in which case additional contraceptive measures are not required. It is possible to start taking it on days 2-5 of the menstrual cycle, but in this case it is recommended to additionally use a barrier method of contraception during the first 7 days of taking the tablets from the first package.
• When switching from other combined contraceptives (COCs, vaginal ring or transdermal patch)
  It is preferable to start taking Dimia® the next day after taking the last inactive tablet (for preparations containing 28 tablets per package) or the next day after taking the last active tablet from the previous package, but in no case later than the next day after the usual 7- daily break (for drugs containing 21 tablets). Taking Dimia® should be started on the day the vaginal ring or patch is removed, but no later than the day when a new ring is to be inserted or a new patch is applied.
• When switching from contraceptives containing only gestagens (mini-pills, injection forms, implant), or from a gestagen-releasing intrauterine contraceptive
  A woman can switch from the “mini-pill” to Dimia® any day (without a break); from an implant or intrauterine contraceptive with gestagen - on the day of its removal, from an injectable contraceptive - on the day when the next injection is due. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills.
• After an abortion in the first trimester of pregnancy
  A woman can start taking the drug immediately after a spontaneous or medical abortion in the first trimester of pregnancy. If this condition is met, the woman does not need additional contraceptive measures.
• After an abortion in the second trimester of pregnancy or childbirth
  Taking the drug can be started 21-28 days after a spontaneous or medical abortion or after childbirth, in the absence of breastfeeding. If use is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the pills. However, if sexual contact has already taken place, pregnancy should be excluded before starting to take Dimia® or you must wait until your first menstruation.

Stopping taking Dimia®
You can stop taking the drug at any time. If a woman is not planning a pregnancy, or if a woman is contraindicated for pregnancy because she is taking medications that are potentially harmful to the fetus, other methods of contraception should be discussed with the doctor.
If a woman is planning a pregnancy, it is recommended to stop taking the drug and wait for natural menstrual bleeding before trying to become pregnant. This will help you more accurately calculate your gestational age and delivery time.
Taking missed pills
Skipping a placebo tablet from the last (4th) row of the blister can be ignored.
However, they should be discarded to avoid inadvertently prolonging the placebo phase. The following recommendations apply only to skipping active tablets. If the delay in taking the drug was less than 24 hours, contraceptive protection is not reduced. The woman should take the missed pill as soon as possible and take the next pill at the usual time.
If you are late in taking your pills more than 24 hours, contraceptive protection may be reduced. The more pills you skip, and the closer the missed pills are to the inactive green placebo pill phase, the higher the chance of pregnancy.
In this case, you can be guided by the following two basic rules:

1. The drug should never be interrupted for more than 7 days;
2. To achieve adequate suppression of the hypothalamic-pituitary-ovarian axis, 7 days of continuous tablet use are required.

In accordance with this, a woman can be given the following recommendations:

• If you miss pills from days 1 to 7:
  A woman should take the last missed pill as soon as she remembers, even if this means taking two pills at the same time. She continues to take her next pills at the usual time. In addition, over the next 7 days it is necessary to additionally use a barrier method of contraception (for example, a condom). If sexual intercourse took place within 7 days before missing a pill, the possibility of pregnancy should be taken into account.
• If you miss pills between days 8 and 14:
  A woman should take the last missed pill as soon as she remembers, even if this means taking two pills at the same time. She continues to take her next pills at the usual time. If a woman has taken her pills correctly in the 7 days preceding the first missed pill, there is no need for additional contraceptive measures. Otherwise, as well as if you miss two or more tablets, you must additionally use barrier methods of contraception (for example, a condom) for 7 days.
• If you miss pills between days 15 and 24:
  The risk of reduced reliability is imminent due to the approaching period of taking the inactive green placebo pills. You must strictly adhere to one of the following two options. However, if during the 7 days preceding the first missed pill, all pills were taken correctly, there is no need to use additional contraceptive methods. Otherwise, the woman must use the first of the following regimens and additionally use a barrier method of contraception (for example, a condom) for 7 days.

1. A woman should take the last missed tablet as soon as she remembers, even if this means taking two tablets at the same time. The next tablets are taken at the usual time until the active tablets in the pack are gone, the 4 green placebo tablets from the last row should be discarded and the tablets from the next pack should be started immediately.
   Withdrawal bleeding is unlikely until the second pack of tablets is gone, but spotting and/or breakthrough bleeding may occur while taking the tablets.
2. A woman can also stop taking active tablets from the current package. She should then take the green placebo pills from the last row for 4 days, including the days she missed pills, and then start taking the pills from the new pack.
   If a woman misses taking active pills and does not experience withdrawal bleeding while taking inactive green placebo pills, pregnancy must be ruled out.

Recommendations for gastrointestinal disorders
In case of severe gastrointestinal disorders, absorption may be incomplete, so additional contraceptive measures should be taken. If you have vomiting or diarrhea within 3-4 hours after taking an active tablet, you should follow the recommendations for skipping tablets. If a woman does not want to change her usual dosing regimen and postpone the onset of menstruation to another day of the week, she should take an additional active tablet.
How to change/delay the onset of withdrawal bleeding
To delay the onset of withdrawal bleeding, a woman should continue taking tablets from the next package of Dimia®, skipping the inactive green tablets from the current package. Thus, the cycle can be extended at will for any period until the active tablets from the second package run out, that is, about 3 weeks later than usual.
If you plan to start your next cycle earlier, you must stop taking the active tablets from the second pack at any time, throw away the remaining active tablets and start taking the inactive green tablets (for a maximum of 4 days), and then start taking the tablets from the new pack. In this case, approximately 2-3 days after taking the last active tablet from the previous package, withdrawal bleeding should begin. While taking the drug from the second package, a woman may experience spotting and/or breakthrough uterine bleeding. Regular use of Dimia® is then resumed after the period of taking the inactive green tablets has ended.
To postpone the onset of withdrawal bleeding to another day of the week, a woman should reduce her next period of taking the inactive green pills by the desired number of days. The shorter the interval, the higher the risk that she will not have withdrawal bleeding and will subsequently experience spotting and/or breakthrough bleeding while taking the pills from the second package.
Use in special categories of patients
Children and teenagers
Dimia® is indicated only after menarche. Available data do not suggest dose adjustment in this group of patients.
Elderly patients
Dimia® is not indicated after menopause.
Patients with liver dysfunction
Dimia® is contraindicated in women with severe liver disease until liver function tests return to normal (see also sections “Contraindications” and “Pharmacological properties”).
Patients with impaired renal function
Dimia® is contraindicated in women with severe renal failure or acute renal failure (see also sections “Contraindications” and “Pharmacological properties”).

Side effect

The following adverse drug reactions (ADRs) were observed during use of the drospirenone/ethinyl estradiol combination.
ADRs are presented according to systemic organ classes in accordance with the MedDRA classification and with the frequency of occurrence: often (> 1/100 and<1/10), нечасто (>1/1000 and<1/100) и редко (>1/10,000 and<1/1000). В пределах каждой группы, выделенной в зависимости от частоты возникновения, НЛР представлены в порядке уменьшения их тяжести. Для дополнительных нежелательных реакций, выявленных только в процессе пострегистрационных наблюдений, и для которых оценку частоты возникновения провести не представлялось возможным, указано «частота неизвестна».

* the frequency of irregular bleeding decreases as the duration of taking Dimia® increases.

Additional Information
Listed below are adverse reactions with a very rare incidence or with delayed symptoms, which are believed to be associated with the use of drugs from the COC group (see also sections “Contraindications” and “Special instructions”).
Tumors

• The incidence of breast cancer diagnosis in women taking COCs is slightly increased. Due to the fact that breast cancer is rare in women under 40 years of age, the increase in breast cancer diagnoses in women taking COCs is small relative to the overall risk of this disease.
• Liver tumors (benign and malignant).

Other states

• women with hypertriglyceridemia have an increased risk of pancreatitis while taking COCs;
• increased blood pressure;
• conditions that develop or worsen while taking COCs, but their relationship has not been proven: jaundice and/or itching associated with cholestasis; cholelithiasis; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; chorea; herpes during pregnancy; hearing loss associated with otosclerosis;
• in women with hereditary angioedema, taking estrogens may cause or aggravate its symptoms;
• liver dysfunction;
• changes in glucose tolerance or effects on insulin resistance;
• Crohn's disease, ulcerative colitis;
• chloasma;
• hypersensitivity (including symptoms such as rash, urticaria).

Interaction
Interaction of COCs with other drugs (enzyme inducers) may lead to breakthrough bleeding and/or decreased contraceptive effectiveness (see section “Interaction with other drugs”).
If any of the side effects indicated in the instructions get worse or you notice any other side effects not listed in the instructions, tell your doctor.

Overdose

No serious adverse events have been reported following overdose. In preclinical studies, there were also no serious adverse effects resulting from overdose.
Symptoms which may occur in case of overdose: nausea, vomiting, spotting vaginal discharge or metrorrhagia.
Treatment. There is no specific antidote; symptomatic treatment should be carried out.

Interaction with other drugs

Effect of other drugs on Dimia®
It is possible to interact with drugs that induce microsomal enzymes, which may result in an increase in the clearance of sex hormones, which, in turn, can lead to breakthrough uterine bleeding and/or a decrease in the contraceptive effect. Women who are treated with such drugs in addition to Dimia® are recommended to use a barrier method of contraception or choose another non-hormonal method of contraception (if long-term use of inducer drugs is necessary).
A barrier method of contraception should be used during the entire period of taking concomitant medications, as well as for 28 days after their discontinuation. If the use of drugs that induce microsomal liver enzymes continues after the end of the active tablets in the Dimia® package, you should start taking Dimia® tablets from the new package without taking green placebo tablets from the old package.

• Substances that increase the clearance of Dimia®(impairing effectiveness by enzyme induction): phenytoin, barbiturates, primidone, carbamazepine, rifampicin and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin, as well as preparations containing St. John's wort.
• Substances with different effects on the clearance of Dimia®
  When used together with Dimia®, many HIV or hepatitis C virus protease inhibitors and non-nucleoside reverse transcriptase inhibitors can both increase and decrease the concentration of estrogens or progestogens in the blood plasma. In some cases, this effect may be clinically significant.
• Substances that reduce the clearance of COCs (enzyme inhibitors)
  Strong and moderate inhibitors of CYP3A4, such as azole antimycotics (eg, itraconazole, voriconazole, fluconazole), verapamil, macrolides (eg, clarithromycin, erythromycin), diltiazem and grapefruit juice may increase plasma concentrations of estrogen or progestogen, or both. Etoricoxib at doses of 60 and 120 mg/day, when coadministered with COCs containing 0.035 mg ethinyl estradiol, has been shown to increase plasma ethinyl estradiol concentrations by 1.4 and 1.6 times, respectively.

Effect of Dimia® on other drugs
COCs may affect the metabolism of other drugs, leading to an increase (for example, cyclosporine) or a decrease (for example, lamotrigine) in their plasma and tissue concentrations.
In vitro, drospirenone is capable of weakly or moderately inhibiting cytochrome P450 isoenzymes CYP1A1, CYP2C9, CYP2C19 and CYP3A4.
Based on in vivo interaction studies in female volunteers taking omeprazole, simvastatin or midazolam as marker substrates, it can be concluded that a clinically significant effect of 3 mg drospirenone on cytochrome P450-mediated drug metabolism is unlikely.
In vitro, ethinyl estradiol is a reversible inhibitor of the isoenzymes CYP2C19, CYP1A1 and CYP1A2, as well as an irreversible inhibitor of the isoenzymes CYP3A4/5, CYP2C8 and CYP2J2. In clinical studies, administration of a hormonal contraceptive containing ethinyl estradiol did not result in any increase or only a slight increase in plasma concentrations of CYP3A4 substrates (eg, midazolam), while plasma concentrations of CYP1A2 substrates may increase slightly (eg, theophylline) or moderate (eg, melatonin and tizanidine).
Other forms of interaction
In patients with preserved renal function, the combined use of drospirenone and angiotensin-converting enzyme inhibitors or non-steroidal anti-inflammatory drugs does not have a significant effect on the concentration of potassium in the blood plasma. However, the combined use of Dimia® with aldosterone antagonists or potassium-sparing diuretics has not been studied. In such cases, the concentration of potassium in the blood plasma must be monitored during the first cycle of taking the drug (see section "Special instructions").

special instructions

If any of the conditions, diseases/risk factors listed below currently exist, the potential risks and expected benefits of using COCs should be carefully weighed in each individual case and discussed with the woman before she decides to start taking the drug. If any of these conditions, diseases or risk factors worsen, intensify, or appear for the first time, a woman should consult her doctor, who may decide whether to discontinue the drug.
Diseases of the cardiovascular system
The results of epidemiological studies indicate a relationship between the use of COCs and an increased incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders). These diseases are rare.
The risk of developing venous thromboembolism (VTE) is greatest in the first year of using such drugs. An increased risk is present after initial use of COCs or resumption of use of the same or different COCs (after a dosing interval of 4 weeks or more). Data from a prospective study involving 3 groups of patients indicate that this increased risk is predominantly present during the first 3 months of drug use. The overall risk of VTE in patients taking low-dose COCs (<0,05 мг этинилэстрадиола) в 2-3 раза выше, чем у небеременных пациенток, которые не принимают КОК, тем не менее, этот риск остается более низким по сравнению с риском ВТЭ при беременности и родах. ВТЭ может угрожать жизни или привести к летальному исходу (в 1-2% случаев).
VTE, manifested as deep vein thrombosis or pulmonary embolism, can occur with the use of any COC.
It is extremely rare when using COCs that thrombosis of other blood vessels occurs, for example, hepatic, mesenteric, renal, cerebral veins and arteries or retinal vessels. There is no consensus regarding the relationship between the occurrence of these diseases and the use of COCs.
Symptoms of deep vein thrombosis (DVT) include the following: unilateral swelling of the lower extremity or along a vein in the lower extremity, pain or discomfort in the lower extremity only when standing or walking, localized warmth in the affected lower extremity, redness or discoloration of the skin on lower limb.
Symptoms of pulmonary embolism (PE) include: difficulty or rapid breathing; sudden cough, including with hemoptysis; sharp pain in the chest, which may intensify with deep inspiration; sense of anxiety; severe dizziness; fast or irregular heartbeat. Some of these symptoms (eg, shortness of breath, cough) are nonspecific and may be misinterpreted as signs of other more or less severe conditions (eg, respiratory tract infection).
Arterial thromboembolism can lead to stroke, vascular occlusion, or myocardial infarction.
Symptoms of a stroke include: sudden weakness or loss of sensation in the face, limbs, especially on one side of the body, sudden confusion, problems with speech and comprehension; sudden unilateral or bilateral vision loss; sudden disturbance in gait, dizziness, loss of balance or coordination; sudden, severe or prolonged headache for no apparent reason; loss of consciousness or fainting with or without an epileptic seizure.
Other signs of vascular occlusion: sudden pain, swelling and slight blue discoloration of the limbs, “acute” abdomen.
Symptoms of a myocardial infarction include: pain, discomfort, a feeling of pressure, heaviness, squeezing, or fullness in the chest, arm, or chest; discomfort radiating to the back, cheekbone, larynx, arm, stomach; cold sweat, nausea, vomiting or dizziness, severe weakness, anxiety or shortness of breath; fast or irregular heartbeat.
Arterial thromboembolism can be life-threatening or fatal. In women with a combination of several risk factors or high severity of one of them, the possibility of their mutual reinforcement should be considered. In such cases, the degree of increase in risk may be higher than with a simple summation of factors. In this case, taking Dimia® is contraindicated (see section “Contraindications”).
The risk of developing thrombosis (venous and/or arterial) and thromboembolism increases:

• with age;
• in smokers (with increasing number of cigarettes or increasing age, the risk increases, especially in women over 35 years of age);

in the presence of:

• obesity (BMI more than 30 kg/m2);
• family history (for example, venous or arterial thromboembolism ever in close relatives or parents under the age of 50 years). In the case of a hereditary or acquired predisposition, the woman should be examined by an appropriate specialist to decide on the possibility of taking COCs;
• prolonged immobilization, major surgery, any operation on the lower limb or major trauma. In these cases, the use of Dimia® should be discontinued. In case of planned surgery, the drug should be stopped at least 4 weeks before the operation and should not be resumed for two weeks after complete restoration of motor activity. Temporary immobilization (eg, air travel lasting more than 4 hours) may also be a risk factor for the development of venous thromboembolism, especially in the presence of other risk factors;
• dyslipoproteinemia;
• arterial hypertension;
• migraine;
• heart valve diseases;
• atrial fibrillation.

The use of any combined hormonal contraceptives increases the risk of developing VTE. The use of drugs containing levonorgestrel, norgestimate or norethisterone is associated with the lowest risk of developing VTE. The use of other drugs, such as Dimia®, may double the risk. The decision to use a drug other than the one with the lowest risk of developing VTE should be made only after discussion with the woman to ensure that she understands that the use of Dimia® is accompanied by the likelihood of developing VTE, and understands how her existing risk factors affect the likelihood of developing VTE, and also understands that in each first year of using the drug, her risk of developing VTE is greatest.
The possible role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism remains controversial.
The increased risk of thromboembolism in the postpartum period should be taken into account. Peripheral circulatory disorders may also occur in diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell anemia.
An increase in the frequency and severity of migraine during the use of COCs (which may precede cerebrovascular events) is grounds for immediate discontinuation of these drugs.
Biochemical indicators indicating a hereditary or acquired predisposition to venous or arterial thrombosis include the following: resistance to activated protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).
When assessing the risk-benefit ratio, it should be taken into account that adequate treatment of the relevant condition can reduce the associated risk of thrombosis. It should also be taken into account that the risk of thrombosis and thromboembolism during pregnancy is higher than when taking low-dose COCs (<0,05 мг этинилэстрадиола).
Tumors
The most significant risk factor for developing cervical cancer is persistent human papillomavirus infection. There are reports of a slight increase in the risk of developing cervical cancer with long-term use of COCs, but the relationship with COC use has not been proven. Controversy remains regarding the extent to which these findings are related to screening for cervical pathology or to sexual behavior (lower use of barrier methods of contraception).
A meta-analysis of 54 epidemiological studies showed that there is a slightly increased relative risk of developing breast cancer diagnosed in women currently taking COCs (relative risk 1.24). The increased risk gradually disappears within 10 years of stopping these drugs. Because breast cancer is rare in women under 40 years of age, the increase in breast cancer diagnoses in current or recent COC users is small relative to the overall risk of breast cancer. The observed increased risk may be due to earlier diagnosis of breast cancer in women using COCs, their biological effects, or a combination of both factors. Women who have used COCs are diagnosed with earlier stages of breast cancer than women who have never used them.
In rare cases, during the use of COCs, the development of benign, and in extremely rare cases, malignant liver tumors, which in some cases led to life-threatening intra-abdominal bleeding, was observed. These conditions should be taken into account when making a differential diagnosis in the event of severe abdominal pain, liver enlargement, or signs of intra-abdominal bleeding.
Tumors can be life-threatening or fatal.
Other states
Clinical studies have shown no effect of drospirenone on plasma potassium concentrations in patients with mild to moderate renal failure. There is a theoretical risk of developing hyperkalemia in patients with impaired renal function with an initial potassium concentration at the upper limit of normal, while simultaneously taking medications that lead to potassium retention in the body. In women with an increased risk of developing hyperkalemia, it is recommended to determine the concentration of potassium in the blood plasma during the first cycle of taking Dimia®.
Women with hypertriglyceridemia (or a family history of this condition) may have an increased risk of developing pancreatitis while taking COCs.
Although slight increases in blood pressure have been described in many women taking COCs, clinically significant increases have rarely been reported. However, if a persistent clinically significant increase in blood pressure develops while taking COCs, these drugs should be discontinued and treatment of arterial hypertension should be initiated. COC use can be continued if normal blood pressure values ​​are achieved with antihypertensive therapy.
The following conditions have been reported to develop or worsen both during pregnancy and while taking COCs, but their relationship with COC use has not been proven: jaundice and/or pruritus associated with cholestasis; cholelithiasis; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; chorea; herpes during pregnancy; hearing loss associated with otosclerosis. Cases of worsening the course of endogenous depression, epilepsy, Crohn's disease and ulcerative colitis during the use of COCs have also been described.
In women with hereditary forms of angioedema, exogenous estrogens may cause or worsen symptoms of angioedema.
Acute or chronic liver dysfunction may require discontinuation of COCs until liver function tests return to normal. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous use of sex hormones, requires discontinuation of COC use.
Although COCs may have an effect on insulin resistance and glucose tolerance, there is no need to change the dose of hypoglycemic drugs in diabetic patients using low-dose COCs (<0,05 мг этинил-эстрадиола). Тем не менее, женщины с сахарным диабетом должны тщательно наблюдаться во время приема КОК.
Chloasma can sometimes develop, especially in women with a history of chloasma during pregnancy. Women with a tendency to chloasma should avoid prolonged exposure to the sun and exposure to ultraviolet radiation while taking COCs.
Laboratory tests
Taking COCs may affect the results of some laboratory tests, including indicators of liver, kidney, thyroid, adrenal function, the concentration of transport proteins in the blood plasma, indicators of carbohydrate metabolism, parameters of coagulation and fibrinolysis. Changes usually do not go beyond normal values. Drospirenone increases the activity of plasma renin and aldosterone, which is associated with its antimineralocorticoid effect.
Medical examinations
Before starting or resuming taking the drug Dimia®, it is necessary to familiarize yourself with the woman’s life history, family history, conduct a thorough medical (including measurement of blood pressure, heart rate, determination of BMI) and gynecological examination (including examination of the mammary glands and cytological examination of scrapings from the cervix), exclude pregnancy. The scope of additional studies and the frequency of follow-up examinations are determined individually. Typically, follow-up examinations should be carried out at least once every 6 months.
The woman should be warned that COCs do not protect against HIV infection (AIDS) and other sexually transmitted diseases.
Reduced efficiency
The effectiveness of COCs may be reduced in the following cases: if active tablets are missed, with vomiting and diarrhea, or as a result of drug interactions.
Poor control of the menstrual cycle
While taking COCs, irregular bleeding may occur (“spotting” and/or “breakthrough” bleeding), especially during the first months of use. Therefore, any irregular bleeding should be assessed only after an adaptation period of approximately three cycles.
If irregular bleeding recurs or develops after previous regular cycles, a thorough diagnostic evaluation should be performed to rule out malignancy or pregnancy.
Some women may not experience withdrawal bleeding while taking green, inactive placebo pills. If the drug is taken as directed, it is unlikely that the woman is pregnant. However, if the drug has not been taken regularly before, or if there are no two withdrawal bleedings in a row, pregnancy should be ruled out before continuing to take the drug.
Lactose
Dimia®, film-coated tablets, contains lactose. Patients with rare hereditary diseases such as galactose intolerance, lactase deficiency and glucose-galactose malabsorption should not take this drug.
Soybeans
Dimia®, film-coated tablets, contains soy lecithin. Patients with peanut and soy allergies should not take this drug.

Impact on the ability to drive vehicles and machinery

Not found.

Release form

Film-coated tablets [set], 3 mg + 0.02 mg.
24 tablets of drospirenone + ethinyl estradiol and 4 placebo tablets in a blister made of PVC/PE/PVDC-aluminum foil.
1 or 3 blisters per cardboard box along with instructions for use. The cardboard box contains a flat cardboard case for storing the blister.

Storage conditions

In a place protected from light at a temperature not exceeding 25 ° C.
Keep out of the reach of children!

Best before date

2 years.
Do not use after the expiration date stated on the package.

Vacation conditions

Dispensed by prescription.

Manufacturer

JSC "Gedeon Richter"
1103 Budapest, st. Dymroyi 19-21, Hungary

Consumer complaints should be sent to:
Moscow Representative Office of JSC Gedeon Richter
119049 Moscow, 4th Dobryninsky lane, building 8,

Tradename

Description

For drospirenone + ethinyl estradiol tablets:
white or almost white, round, biconvex film-coated tablets, about 6 mm in diameter; On one side of the tablet there is an engraving “G73”.
For placebo tablets:
Green, round, biconvex film-coated tablets, diameter 6 mm.

Pharmacotherapeutic group

Combined contraceptive (estrogen + gestagen)

ATX Code:

Release form, composition and packaging

Active ingredient	1 film-coated tablet
Drospirenone	3 mg
Ethinyl estradiol	0.02 mg
Excipients
Core: lactose monohydrate, corn starch, pregelatinized corn starch, macrogol and polyvinyl alcohol copolymer, magnesium stearate; Film shell: Opadry II white 85G18490 (polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, soy lecithin).
Excipients (placebo tablet)
Core: microcrystalline cellulose, anhydrous lactose, pregelatinized corn starch, magnesium stearate, colloidal silicon dioxide, anhydrous. Film casing: Opadry II 85F21389 green (polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, indigo carmine aluminum varnish (E132), quinoline yellow aluminum varnish (E104), iron dioxide black (E172), sunset yellow FCF aluminum varnish (E110)).
Release form: 24 tablets of the drug and 4 tablets of placebo in a blister pack made of PVC/PE/PVDC film and aluminum foil. 1 or 3 blister packs in a cardboard case, enclosed together with instructions for medical use in a cardboard box.

Structural formula, gross formula and chemical name

Pharmacological properties

A combined oral contraceptive (COC) containing ethinyl estradiol and the progestin drospirenone. At a therapeutic dose, drospirenone also has antiandrogenic and weak antimineralocorticoid effects. Does not have estrogenic, glucocorticoid and antiglucocorticoid activity. Thus, drospirenone has a pharmacological profile close to the natural hormone progesterone.
Clinical studies have shown that the antimineralocorticoid properties of Dimia® lead to a weak antimineralocorticoid effect.
It has antiandrogenic activity, which leads to a reduction in the formation of acne and a decrease in the production of sebaceous glands, and does not affect the increase in the formation of sex hormone-binding globulin caused by ethinyl estradiol (inactivation of endogenous androgens).
: 0.31 (upper 95% confidence interval: 0.85). The contraceptive effect of the drug is based on the interaction of various factors, the most important of which are inhibition of ovulation and changes in the endometrium.

Pharmacokinetics

Drospirenone

Suction
When taken orally, drospirenone is rapidly and almost completely absorbed. The maximum serum concentration of drospirenone, equal to 37 ng/ml, is achieved 1-2 hours after a single oral dose. Bioavailability ranges from 76 to 85%. Food intake does not affect the bioavailability of drospirenone.

Distribution
Following oral administration, serum levels of drospirenone decrease with a terminal half-life of 31 hours. Drospirenone is observed to bind to serum albumin, but the drug does not bind to sex hormone binding globulin (SHBG) or corticosteroid binding globulin (CBG). Only 3-5% of total serum concentrations of active substance are present as free steroid. The ethinyl estradiol-induced increase in SHBG does not affect the binding of drospirenone to serum proteins. The average apparent V d of Drospirenone is 3.7 ± 1.2 l/kg.
During one treatment cycle, the maximum serum Cmax of drospirenone (approximately 70 ng/ml) is achieved after 8 days of treatment. Serum concentrations of drospirenone increase by approximately 3 orders of magnitude due to the final half-life ratio and dosing interval.

Metabolism
Drospirenone is actively metabolized after oral administration. The main metabolites in the blood plasma are the acid form of drospirenone, formed by opening of the lactone ring, and 4,5-dihydro-drospirenone-3-sulfate, both formed without the participation of the P450 (CYP) system. Drospirenone is slightly metabolized by CYP3A4 and is capable of inhibiting this isoenzyme, as well as CYP1A1, CYP2C9 and CYP2C19 in vitro.

Removal
The rate of metabolic clearance of drospirenone in serum is 1.5±0.2 ml/min/kg. Drospirenone is excreted only in trace amounts unchanged. Drospirenone metabolites are excreted in feces and urine in a ratio of approximately 1.2:1.4. T1/2 for excretion of metabolites in urine and feces is approximately 40 hours.

Ethinyl estradiol

Suction
Ethinyl estradiol, after oral administration, is rapidly and completely absorbed. Cmax in blood serum after a single dose of 33 pg/ml is achieved after 1-2 hours. After presystemic conjugation and presystemic metabolism in the small intestine and liver, absolute bioavailability is 60%. Concomitant food intake reduced the bioavailability of ethinyl estradiol in approximately 25% of people studied, whereas no similar changes were observed in other people.

Distribution
Serum ethinyl estradiol levels decrease in two phases, with a final pharmacokinetic phase characterized by T1/2 of approximately 24 hours. Ethinyl estradiol binds to albumin to approximately 98.5% and induces an increase in serum SHBG and DSG concentrations. The apparent V d is approximately 5 l/kg.
The C ss state is achieved during the second half of the treatment cycle, with serum ethinyl estradiol levels increasing by a factor of approximately 2.0-2.3.

Metabolism
Ethinyl estradiol undergoes presystemic conjugation in the mucosa of the small intestine and in the liver. Ethinyl estradiol is primarily metabolized by aromatic hydroxylation, resulting in the formation of a variety of hydroxylated and methylated metabolites, presented both as free metabolites and as conjugates with glucuronic and sulfuric acids. Ethinyl estradiol is completely metabolized. The rate of metabolic clearance of ethinyl estradiol is 5 ml/min/kg.

Removal
Ethinyl estradiol is practically not excreted unchanged. Ethinyl estradiol metabolites are excreted in urine and bile in a ratio of 4:6. Half life of metabolites is approximately 1 day. Elimination T1/2 is 20 hours.

Pharmacokinetics in special groups of patients

Patients with impaired renal function. C ss of drospirenone in serum in women with mild renal failure: (creatinine clearance 50-80 ml/min) was comparable to that in women with normal renal function (creatinine clearance>80 ml/min). Serum drospirenone levels were on average 37% higher in women with moderate renal impairment (CrCl = 30-50 ml/min) compared to women with normal renal function. Drospirenone therapy was well tolerated by women with both mild and moderate renal impairment.
Treatment with drospirenone did not have a clinically significant effect on serum potassium levels.

Patients with impaired liver function.
In a single-dose study, total clearance in volunteers with moderate hepatic impairment was approximately 50% reduced compared with that in subjects with normal hepatic function.
The observed decrease in clearance of drospirenone in volunteers with moderate hepatic impairment does not lead to any significant differences in serum potassium concentration. Even with diabetes and concomitant treatment with spironolactone (two factors that can precipitate hyperkalemia in the patient), there was no increase in serum potassium concentrations above the ULN. It can be concluded that the combination of drospirenone/ethinyl estradiol is well tolerated in patients with moderate hepatic impairment (Child-Pugh class B).

Ethnic groups. There were no clinically relevant differences in the pharmacokinetics of drospirenone or ethinyl estradiol between Japanese and Caucasian women.

Indications for use

• Oral contraception.

The drug has a positive effect on symptoms associated with fluid retention in the body, as well as acne and seborrhea, due to its antimineralocorticoid and antiandrogenic effects.

Directions for use and doses

The tablets must be taken every day at approximately the same time, if necessary, with a small amount of liquid, in the order indicated on the package. It is necessary to take 1 tablet/day for 28 days in a row. Each subsequent package should begin after taking the last tablet from the previous package. Withdrawal bleeding usually begins on day 23 after taking placebo tablets (last row) and may not end by the time the next pack is started.

If you have not previously used hormonal contraceptives (in the last month)
Taking Dimia® begins on the first day of a woman’s natural menstrual cycle (i.e., on the first day of menstrual bleeding).

If you are replacing another PDA, vaginal ring, or transdermal patch
It is preferable for a woman to start taking Dimia ® the next day after the usual hormone-free interval in the previous combined contraceptive regimen. When replacing a vaginal ring or transdermal patch, it is advisable to start taking Dimia ® on the day the previous product was removed; in such cases, taking Dimia ® should begin no later than the day of the planned replacement procedure.

In case of replacement of a method using only gestagens (mini-pills, injection forms, implants) or an intrauterine system (IUD) with the release of gestagens

A woman can switch from the mini-pill on any day (from an implant or IUD on the day of its removal, from an injectable form - from the day when the next injection was due). However, in all these cases it is advisable to use additionally during the first 7 days of taking the tablets.

After termination of pregnancy in the first trimester

The woman can start taking it immediately. If this condition is met, there is no need for additional contraceptive measures.

After childbirth or termination of pregnancy in the second trimester

It is advisable for a woman to start taking Dimia ® on days 21-28 after childbirth or termination of pregnancy in the second trimester. If taken later, it is necessary to use additionally during the first 7 days of taking the tablets. If you have sexual intercourse, pregnancy should be excluded before starting to take the drug or you must wait until your first menstruation.

Taking missed pills

Omission of a placebo tablet from the last (4th) row of the blister can be ignored. However, they should be discarded to avoid inadvertently prolonging the placebo phase. The instructions below apply only to missed active tablets:
If the delay in taking the pill is less than 12 hours, contraceptive protection is not reduced. A woman should take the missed pill as soon as possible and take the next pill at the usual time. If the delay in taking the pills is more than 12 hours, contraceptive protection may be reduced. Correcting missed pills should be guided by the following two simple rules:

1. Taking pills should not be stopped for more than 7 days.
2. To achieve adequate suppression of the hypothalamic-pituitary-ovarian system, 7 days of continuous tablet use are necessary.

Accordingly, the following advice can be given in daily practice:

Week 1
You should take the last missed tablet as soon as possible, even if this means taking two tablets at the same time. The next tablet is taken at the usual time. Additionally, a barrier method of contraception must be used for the next 7 days. If sexual intercourse took place within 7 days before missing a pill, the possibility of pregnancy must be taken into account. The more pills you miss and the closer this skip is to the 7-day break in taking the drug, the higher the risk of pregnancy.

Week 2
You should take the last missed tablet as soon as possible, even if this means taking two tablets at the same time. The next tablet is taken at the usual time. If a woman has taken the pills correctly over the previous 7 days, there is no need to use additional contraception. However, if she has missed more than 1 tablet, additional precautions must be taken in the next 7 days.

Week 3
The likelihood of a decrease in the contraceptive effect is significant due to the approaching phase of placebo pills. However, by adjusting the schedule for taking pills, you can prevent a decrease in contraceptive protection. If you follow any of the following two tips, you will not need additional methods of contraception if you have taken all your pills correctly in the previous 7 days before missing a pill. If this is not the case, she should follow the first of the two methods and also use additional precautions for the next 7 days.

1. You should take the last missed tablet as soon as possible, even if this means taking two tablets at the same time. The next tablets are taken at the usual time until the active tablets are gone. You should not take 4 placebo tablets from the last row; you should immediately start taking tablets from the next pack. Most likely, there will be no withdrawal bleeding until the end of the second pack, but spotting or breakthrough uterine bleeding may occur on the days of taking the pills.
2. The woman may be advised to stop taking active tablets from the started pack. Instead, she should take the placebo pills from the last row for 4 days, including the days she missed pills, and then start taking the pills from the next pack.
   If you miss taking pills and there is no withdrawal bleeding in the placebo pill phase, pregnancy must be ruled out.

Gastrointestinal disorders
In case of severe gastrointestinal reactions (such as vomiting or diarrhea), absorption may be incomplete and additional contraceptive measures must be used.
If vomiting occurs within 3-4 hours after taking the active tablet, you should take a new replacement tablet as soon as possible. If possible, the next tablet should be taken within 12 hours after the usual dosing time. If more than 12 hours are missed, if possible, you must follow the rules for taking the drug specified in the section “Taking missed tablets.” If the patient does not want to change the normal regimen of taking the drug, she should take an additional tablet (or several tablets) from a different package.

How to delay withdrawal bleeding
To delay the onset of menstruation, you must skip taking placebo tablets from the started package and start taking active Dimia ® tablets from a new package without interruption. A delay is possible until the end of the tablets in the second package.
During the lengthening of the cycle, spotting bloody discharge from the vagina or uterine breakthrough bleeding may occur. Regular use of Dimia ® ends after the placebo phase.
To move the start of your period to another day of the week on your regular schedule, shorten the upcoming placebo pill phase by as many days as necessary. The shorter the interval, the higher the risk that there will be no “withdrawal” bleeding, and while taking the second package, spotting and breakthrough bleeding will be observed (as well as in the case of a delay in the onset of menstruation).

Side effect

Undesirable effects of the drug Dimia

Often (≥ 1/100 to 1/10)	Uncommon (≥ 1/1000 to 1/100)	Rare (≥ 1/10000 to 1/1000)
- headache, – emotional lability; – depression; - nausea; – menstrual irregularities (metrorrhagia, amenorrhea); – intermenstrual bleeding; - chest pain.	- dizziness; – migraine; – nervousness; – drowsiness; – decreased mood; – paresthesia; – hypertension; - phlebeurysm; – soreness and tension of the mammary glands; – fibrocystic changes in the mammary gland; - nausea; - vomit; – gastritis; - abdominal pain; – dyspepsia; – flatulence; – diarrhea; – acne; – skin itching; – dry skin; - back pain; – pain in the limbs; – muscle cramps; – decreased libido; – vaginal discharge; – vaginal canlidiasis; – dryness in the vagina; – vaginitis; – menstrual irregularities (dysmenorrhea, hypomenorrhea, menorrhagia); – asthenia; – increased sweating; – fluid retention in the body; – increase in body weight.	– loss of body weight, – increased appetite, – anorexia, – urticaria, – anemia, – thrombocytopenia, – hyperkalemia, – hyponatremia, – anorgasmia, - insomnia, – vertigo, – tremor, - nose bleed, - fainting, – thromboembolism, – venous thrombosis/thromboembolism, – arterial thrombosis/thromboembolism, – conjunctivitis, – dry eyes, – poor tolerance to contact lenses, – tachycardia, - arterial hypertension, – liver tumors, - Crohn's disease, - nonspecific ulcerative colitis, – epilepsy, – endometriosis, – uterine fibroids, – porphyria, – systemic lupus erythematosus, – herpes of pregnant women, - Sydenham's chorea, – hemolytic uremic syndrome, – cholestatic jaundice, – chloasma, – dry skin, – acne or contact dermatitis, – angioedema, – eczema, – hypertrichosis, – photodermatitis, – erythema nodosum, – erythema multiforme, – breast cyst, – breast hyperplasia, – painful sexual intercourse, – postcoital bleeding, – withdrawal bleeding, – cervical polyps, – endometrial atrophy, - ovarian cyst, – enlargement of the uterus, – increased libido.

Contraindications

• pregnancy;
• breastfeeding period;
• the presence of venous thrombosis currently or in history (for example, deep vein thrombosis, pulmonary embolism);
• current or history of arterial thrombosis (eg, myocardial infarction) or previous conditions (eg, angina and transient ischemic attack);
• cerebrovascular diseases currently or in history; presence of severe or
• multiple risk factors for arterial thrombosis;
• diabetes mellitus with vascular complications;
• severe arterial hypertension;
• severe dyslipoproteinemia;
• hereditary or acquired predisposition to venous or arterial thrombosis, such as resistance to APC (activated protein C), antithrombin 3 deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant);
• pancreatitis with severe hypertriglyceridemia, incl. in the anamnesis;
• severe liver disease (before normalization of liver tests) currently or in history; severe chronic renal failure or acute renal failure;
• liver tumors (benign or malignant), currently or in history;
• hormone-dependent malignant diseases of the reproductive system (genital organs, mammary glands) or suspicion of them;
• vaginal bleeding of unknown origin;
• migraine with local neurological symptoms in history;
• galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome;
• hypersensitivity to the active substance or any of the excipients.

Pregnancy and lactation

If pregnancy occurs while taking Dimia ® , the drug must be discontinued immediately. Epidemiological studies have shown neither an increase in the risk of childbirth for children in women who took COCs before pregnancy, nor a teratogenic effect when COCs were inadvertently taken during pregnancy. No such studies have been conducted with the drug.
COCs may affect lactation because they can reduce the quantity and change the composition of breast milk. Therefore, the use of PDAs cannot be recommended until a breastfeeding woman has completely stopped breastfeeding. Small amounts of contraceptive hormones or their metabolites may be excreted in milk during the use of COCs. These amounts may affect the child.

special instructions

If any of the conditions/risk factors listed below currently exist, the potential risks and expected benefits of using COCs should be carefully weighed in each individual case and discussed with the woman before she decides to start taking the drug. If any of these conditions or risk factors worsen, intensify, or appear for the first time, a woman should consult her doctor, who may decide whether to discontinue the COC.

Circulatory system disorders
Epidemiological studies have shown that the incidence of VTE (venous thromboembolism) in women without risk factors for VTE taking low-dose estrogen COCs (< 50 мкг этинилэстрадиола) составляет примерно от 20 случаев на 100 000 женщин в год (для левоноргестрел-содержащих КПК второго поколения) или до 40 случаев на 100 000 женщин в год (для дезогестрел/гестоден- содержащих КОК третьего поколения). Это сравнимо с цифрами от 5 до 10 случаев на 100 000 женщин, не использующих контрацептивы, и 60 случаев на 100 000 беременностей.
Use of any combined oral contraceptives is associated with an increased risk of venous thromboembolism comparable to that without use. The additional risk is greatest during the first year of combined oral contraceptive use. Venous thromboembolism is fatal in 1-2% of cases.
Epidemiological studies have also associated COC use with an increased risk of arterial thromboembolism (myocardial infarction, transient ischemic attack).
In women taking combined oral contraceptives, extremely rare cases of thrombosis of other blood vessels, such as the hepatic, mesenteric, renal arteries and veins, the central retinal vein and its branches, have been described.

Symptoms of venous or arterial thrombosis, thromboembolism, or cerebrovascular disease may include:

• unusual unilateral pain and/or swelling of the limb;
• sudden severe chest pain, with or without radiation to the left arm; sudden shortness of breath;
• sudden attack of coughing;
• any unusual, severe, prolonged headache;
• sudden partial or complete loss of vision;
• diplopia;
• slurred speech or aphasia;
• dizziness;
• loss of consciousness with or without a seizure;
• weakness or extreme loss of sensation that suddenly appears on one side or in one part of the body;
• movement disorders;
• symptom of “acute abdomen”.

The risk of complications associated with venous thromboembolism when taking COCs increases:

• with age;
• in the presence of a family history (venous or arterial thromboembolism ever in close relatives or parents at a relatively young age); if a hereditary predisposition is suspected, the woman needs to consult a specialist before prescribing a COC;
• after prolonged immobilization, major surgery, any leg surgery or major trauma. In these situations, it is recommended to stop taking the drug (in the case of planned surgery, at least four weeks before it) and not to resume taking it for two weeks after the end of immobilization. Additionally, it is possible to prescribe antithrombotic therapy if the pills were not stopped within the recommended time frame;
• obesity (body mass index more than 30 mg/m2);
• There is no consensus on the possible role of varicose veins and superficial vein thrombophlebitis in the onset or progression of venous thrombosis.

The risk of arterial thrombotic complications of thrombosis of cerebrovascular disease in women taking COCs increases:

• with age;
• in smokers (women over 35 years of age are strictly not recommended to smoke if they want to use COCs);
• with dyslipoproteinemia;
• for hypertension;
• for migraines;
• for diseases of the heart valves;
• with atrial fibrillation.

The presence of one of the serious risk factors or multiple risk factors for arterial or venous disease, respectively, may be a contraindication. Women using COCs should consult a doctor immediately if symptoms of possible thrombosis occur. In cases of suspected or confirmed thrombosis, COC use should be discontinued. It is necessary to select an adequate method of contraception due to the teratogenicity of anticoagulant therapy (coumarins).
The increased risk of thromboembolism in the postpartum period should be taken into account.

Other diseases

Other diseases that are associated with severe vascular pathology include diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis), and sickle cell disease.
An increase in the frequency and severity of migraines during the use of COCs (which may precede cerebrovascular events) may be grounds for immediate discontinuation of these drugs.
An increased risk of cervical cancer with long-term use of combined oral contraceptives has been reported in some epidemiological studies. Its connection with the use of COCs has not been proven. Controversy remains over the extent to which these findings are attributable to sexual behavior and other factors such as human papillomavirus (HPV).

Mammary cancer

A meta-analysis of 54 epidemiological studies demonstrated that there was a slightly increased relative rate (RR=1.24) of breast cancer diagnosed in women who were using combined oral contraceptives at the time of the study. Its connection with the use of COCs has not been proven. The observed increased risk may be a consequence of earlier diagnosis of breast cancer in women using combined oral contraceptives. Breast cancer in women who had ever used combined oral contraceptives was clinically less severe than in women who had never used such drugs. In rare cases, the development of benign liver tumors has been observed during the use of COCs, and in extremely rare cases, the development of malignant liver tumors. In some cases, these tumors lead to life-threatening intra-abdominal bleeding. If severe abdominal pain, liver enlargement, or signs of intra-abdominal bleeding occur when making a differential diagnosis in a woman taking COCs, the likelihood of developing a liver tumor should be taken into account.

Other states

The progestin component in Dimia ® is an aldosterone antagonist with potassium-sparing properties. In most cases, potassium levels are not expected to increase. But in a clinical study in some patients with mild to moderate renal impairment, concomitant use of potassium-sparing drugs did not significantly increase serum potassium levels when taking drospirenone. It is therefore recommended to check serum potassium levels during the first cycle of treatment in patients with renal failure whose pre-treatment serum potassium levels were at the upper limit of normal and who are additionally using potassium-sparing drugs.
In women with hypertriglyceridemia or a family history of this disease, an increased risk of developing pancreatitis while taking COCs cannot be excluded. Although slight increases in blood pressure have been reported in many women taking combined oral contraceptives, clinically significant increases have rarely been observed. Only in rare cases is the immediate abolition of the CCP justified. If, while taking a COC with existing arterial hypertension, persistently or significantly elevated blood pressure does not adequately respond to antihypertensive treatment, you should stop taking the COC.
The following conditions have been reported to develop or worsen both during pregnancy and while taking COCs, but their relationship with COC use has not been proven: jaundice and/or pruritus associated with cholestasis, gallstone formation, porphyria, systemic red lupus, hemolytic uremic syndrome, Sydenham chorea, gestational herpes, hearing loss associated with otosclerosis. In women prone to angioedema, exogenous estrogens may induce or worsen the symptoms of angioedema.
Acute or chronic liver dysfunction may require discontinuation of COCs until liver function tests return to normal. Recurrent cholestatic jaundice and/or itching associated with cholestasis, which developed for the first time during pregnancy or previous use of sex hormones, requires discontinuation of COC use. Although COCs may have an effect on insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetic patients using combined oral contraceptives (containing< 0.05 мг этинилэстрадиола). Тем не менее, женщины с сахарным диабетом должны тщательно наблюдаться, особенно на ранней стадии приема КПК.
Cases of Crohn's disease and ulcerative colitis have also been described with the use of COCs, however, the connection with taking the drugs has not been proven.
Worsening of endogenous depression, epilepsy, Crohn's disease and ulcerative colitis has been reported with COC use.
In rare cases, chloasma may develop, especially in women with skin pigmentation during pregnancy. Women with a tendency to chloasma should avoid prolonged exposure to the sun and exposure to ultraviolet radiation while taking COCs. The drug contains 48.53 mg of lactose per tablet and 37.26 mg of anhydrous lactose per inactive tablet. Patients with rare hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption who are on a lactose-free diet should keep this in mind.
Women who are allergic to soy lecithin may experience mild allergic reactions.

Medical examinations/consultations

Before starting or resuming taking Dimia, a woman is recommended to undergo a thorough general medical examination (including anamnesis) and exclude pregnancy. Blood pressure should be measured and a physical examination performed. The doctor should be guided by contraindications for taking COCs and warnings. The woman should be instructed to read the leaflet carefully and follow the advice given. The frequency and nature of examinations should be based on specific practical guidelines and adapted to the characteristics of each woman.

PDAs do not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Reduced efficiency

The effectiveness of COCs may be reduced if pills are missed, gastrointestinal disorders, or concomitant medications are taken.

Reduced cycle control

While taking all COCs, irregular bleeding (spotting or withdrawal bleeding) may occur, especially during the first months of use. Therefore, assessing any irregular bleeding is only meaningful after an adaptation period of approximately three cycles.

If irregular bleeding recurs or develops after previous regular cycles, then non-hormonal causes should be considered and adequate diagnostic measures should be taken to exclude malignancy or pregnancy. These may include curettage.

In some women, withdrawal bleeding may not develop during a break from taking the pills. If COCs are taken as directed, it is unlikely that the woman will be pregnant. However, if COCs have not been taken regularly before or if there are no two withdrawal bleedings in a row, pregnancy should be ruled out before continuing to take COCs.

Impact on the ability to drive vehicles and operate machinery

There have been no studies examining the effect of the drug on the ability to drive a car or operate machinery with an increased risk of injury.

Overdose

Symptoms: nausea, vomiting, slight vaginal bleeding in young girls.
Treatment: symptomatic.

Interaction with other drugs

Some drugs, due to the induction of microsomal enzymes, can increase the clearance of sex hormones (hydantoin, phenytoin, barbiturates, primidone, carbamazepine and rifampicin; the same effect is also possible with oxycarbazepine, topiramate, felbamate, ritonavir, griseofulvin and herbal remedy based on St. John's wort (Hypericum perforatum)). Maximal induction of liver microsomal enzymes usually does not occur for 2–3 weeks, but may then persist for at least 4 weeks after drug therapy is stopped. The possible effects of HIV protease inhibitors (eg, ritonavir) and non-nucleoside reverse transcriptase inhibitors (eg, nevirapine) and their combinations on hepatic metabolism have been reported.
Co-administration with certain antibiotics, such as penicillins and tetracyclines, reduces the enterohepatic recirculation of estrogens, which may lead to a decrease in ethinyl estradiol concentrations.
Women receiving any of the above classes of drugs or individual active substances should use a barrier method of contraception in addition to Dimia ® or switch to any other method of contraception. Women receiving continuous treatment with drugs containing active substances that affect liver enzymes must additionally use a non-hormonal method of contraception for 28 days after their discontinuation.
Women receiving rifampicin therapy, in addition to taking COCs, should use a barrier method of contraception and continue to use it for 28 days after stopping treatment with rifampicin. If taking concomitant medications lasts longer than the expiration date of the active tablets in the package, the placebo tablets should be discarded and immediately begin taking the active tablets from the next package.
The main metabolism of drospirenone in human plasma occurs without the involvement of the CYP system. Inhibitors of this enzyme system therefore do not affect the metabolism of drospirenone.
Oral contraceptives may affect the metabolism of certain other active compounds. In addition, their concentrations in plasma and tissues may change, either increasing (for example, cyclosporine) or decreasing (for example, lamotrigine).
In female volunteers taking omeprazole, simvastatin and midazolam as tracer substrates, the effect of drospirenone 3 mg on the metabolism of other active substances is unlikely.
In patients with renal failure, simultaneous administration of drospirenone and ACE inhibitors or NSAIDs does not have a significant effect on serum potassium levels. However, the simultaneous use of Dimia ® and aldosterone antagonists or potassium-sparing diuretics has not been studied. In this case, it is necessary to study the level of potassium in the serum during the first cycle of taking the drug.
Co-administration of drugs should be discussed to identify possible drug interactions.
Taking hormones for contraception may affect the results of certain laboratory tests, including biochemical indicators of liver, thyroid, adrenal and kidney function, as well as levels of plasma transport proteins such as corticosteroid binding globulin and lipid/lipoprotein fractions, indicators of carbohydrate metabolism, coagulation and fibrinolysis. Changes usually occur within laboratory limits.
Due to its slight antimineralocorticoid activity, drospirenone increases the activity of plasma renin and aldosterone.

Storage conditions and expiration dates

The drug should be stored in its original packaging, out of the reach of children, protected from light at a temperature of 15° to 25°C. Shelf life – 2 years.

Conditions for dispensing from pharmacies

The drug is available with a prescription.

Analogs

The decision to change the drug is made by the attending physician; do not take it yourself.

Manufacturer

JSC "Gedeon Richter" 1103, Budapest, st. Demrei, 19-21, Hungary.