Hormone drospirenone in various drugs. Combined contraceptives: subtleties of use Preparations with drospirenone
What is drospirenone? It is a synthetic hormone, similar in properties to natural progesterone. The agent is a derivative of spirinolactone.
This substance belongs to the group of oral contraceptives. It is usually used in combination with other hormones. It has a therapeutic effect on androgen-dependent diseases (acne, serobeya), removes sodium ions and excess fluid from the body. In this regard, it normalizes blood pressure, swelling subsides, body weight decreases, soreness in the mammary glands disappears. Also in the process of treatment, the drug reduces the level of cholesterol in the blood and LDL, slightly increases the concentration of triglycerides.
For women: during menopause, the likelihood of colon cancer, hyperplasia and endometrial cancer is significantly reduced.
Drospirenone fights sleep disturbance, irritability with premenstrual syndrome, depression.
And, of course, the remedy is used to protect against unwanted pregnancy.
IMPORTANT! Drugs with drospirenone are prescribed by a doctor. Do not self-medicate!
Indications for use
Drospirenone has multidirectional properties: progestogenic, antiandrogenic, antigonadotropic, antimineralocorticoid.
It is prescribed for:
- Contraception (in combination with other hormones)
- Complex therapy for the prevention of postmenopausal osteoporosis
- Climacteric disorders (elimination of hot flashes, sweating)
- Severe PMS symptoms
- Acne treatment, blackheads
- folate deficiency
- Fluid retention in the body
- Involutional changes in the genitourinary tract (in women with an unremoved uterus)
Contraindications
- Allergic reactions to drospirenone
- porfiria
- Tendency to form blood clots
- Liver failure
- Lactation (the period of breastfeeding)
- Vaginal bleeding of unknown origin
- Breast (or genital) cancer
- Pregnancy
- Thromboembolism or thrombophlebitis
Side effects
- Allergy
- Dizziness, headaches
- arterial hypertension
- puffiness
- Thrombophlebitis, thrombi in retinal veins, thromboembolism pulmonary artery or cerebral vessels
- Calculous cholecystitis
- Depression, apathy, drowsiness, insomnia
- Vomiting, nausea
- Weight jumps
- Decreased visual acuity
- Vaginal discharge (bloody or unusual consistency)
- Decreased libido
- Chloasma
- Varicose veins, cramps
- Galactorrhea
- Alopecia
- Breast pain and swelling
Overdose: symptoms
- Nausea
- Vomit
- Vaginal bleeding
Instruction (method of application and dosage)
Drospirenone is prescribed according to different treatment regimens, which depend on which combination the hormone is in the drug.
Usually hormones are taken once a day at exactly the same time.
IMPORTANT! Therapy is prescribed by a doctor.
The duration and nuances of treatment should also be discussed by your doctor.
Drospirenone is available from pharmacies by prescription only.
Interaction
Drospirenone reduces the effectiveness of anabolic steroids and drugs that stimulate the smooth muscles of the uterus.
Reduces the effectiveness of drugs that enhance liver enzymes (barbiturates, carbamazepine, oscarbazepine, hydantoin derivatives, primidone, rifampicin, topiramate, griseofulvin, felbamate).
Some antibiotics may interfere with the metabolism of drospirenone.
Contraceptives with drospirenone (analogues, cost)
The most common question about this remedy on the Internet is: “What contraceptives contain?” Here is a list of drugs:
Angelique(Drospirenone + Estradiol) 28 pcs., 2 mg - 1160-1280 rub.
Dailla
(Drospirenone + Ethinylestradiol) 28 pcs. – 900-1000 rub.
Modell Pro(Drospirenone + Ethinylestradiol)
Simicia(Drospirenone + Ethinylestradiol)
Modell Trend(Drospirenone + Ethinylestradiol)
Midian(Drospirenone + Ethinylestradiol) Midiana, 21 pcs. – 680-700 rub.
(Drospirenone + Ethinylestradiol) 21 pcs. – 1000-1300 rub.
Vidor(Drospirenone + Ethinylestradiol)
Zentiva(Drospirenone + Ethinylestradiol)
Jess Plus
(Drospirenone + Ethinylestradiol with the addition of calcium levomefolicate)
Dimia, 28 pcs. – 980-990 rub.
Composition of COC
Hormonal contraceptives from the COC category (combined oral contraceptives) are a combination of two hormones (estrogen + gestagen).
Estrogen is always the same in all preparations and is presented as ethinyl estradiol. But as a progesterone, both drosperinone and another active substance can be used.
Distinctive features of drospirenone
- Good antimineralcorticoid activity
- Helps block steroid hormone binding to mineralocorticoid receptors
Gestodene or Drospirenone?
Both synthetic hormones are effective. Side effects from taking them are minimized. Differences:
Preparations with gestodene are prescribed for dysmenorrhea, as well as for setting a regular menstrual cycle.
Drospirenone reduces the severity of PMS, relieves acne and removes excess fluid from the body. However, there is a risk of developing thromboembolism and hyperkalemia with long-term use of drugs with this substance.
Desogestrel or Drospirenone?
Desogestrel is used to eliminate dysmenorrhea.
While taking drugs with drospirenone, the risk of weight gain is slightly higher.
BUT! In any case, only a qualified specialist should decide what suits you best. Treatment with hormonal drugs is no joke.
Formula: C24H30O3, chemical name: (6R,7R,8R,9S,10R,13S,14S,15S,16S,17S)-1,3",4",6,6a,7,8,9,10,11,12 ,13,14,15,15a,16-hexadecahydro-10,13-dimethylspiro-cyclopenta[a]phenanthrine-17.2"(5H)-furan]-3.5"(2H)-dione).
Pharmacological group: hormones and their antagonists / estrogens, gestagens; their homologues and antagonists.
Pharmachologic effect: gestagenic, antiandrogenic, antigonadotropic, antimineralocorticoid.
Pharmacological properties
Drospirenone is a derivative of spironolactone. Drospirenone has a therapeutic effect on androgen-dependent diseases: seborrhea, acne, androgenetic alopecia. Drospirenone increases the excretion of water and sodium ions, which may prevent weight gain, blood pressure, soreness of the mammary glands, swelling and other symptoms that are associated with fluid retention. Drospirenone does not have androgenic, estrogenic, antiglucocorticosteroid, glucocorticosteroid activity, does not affect insulin resistance and glucose tolerance, which, together with antiandrogenic and antimineralocorticoid effects, provides it with a pharmacological and biochemical profile that is similar to natural progesterone. Drospirenone reduces the rise in triglyceride levels, which is caused by estradiol. The mechanism of action of drospirenone is still unclear. When administered orally, drospirenone is completely and rapidly absorbed. The bioavailability of drospirenone is 76 - 85%. Food intake does not affect bioavailability. The maximum concentration is reached after 1 hour and is 22 ng / ml with multiple and single doses of 2 mg of drospirenone. This is followed by a biphasic decrease in plasma levels of drospirenone with a terminal elimination half-life of approximately 35 to 39 hours. Approximately 10 days later daily intake drospirenone reaches equilibrium concentration. Due to the long half-life of drospirenone, the steady-state concentration is 2 to 3 times the concentration at a single dose. Drospirenone binds to plasma albumin and does not bind to corticoid-binding globulin and globulin, which binds sex hormones. Approximately 3 - 5% of drospirenone does not bind to proteins. The main metabolites of drospirenone are 4,5-dihydrodrospirenone-3-sulfate and the acidic form of drospirenone, which are formed without the participation of the cytochrome P450 system. The clearance of drospirenone is 1.2 - 1.5 ml / min / kg. Drospirenone is excreted mainly in the form of metabolites with feces and urine in a ratio of 1.4: 1.2, with a half-life of approximately 40 hours; an insignificant part of drospirenone is excreted unchanged.
Indications
As part of combined treatment: prevention of postmenopausal osteoporosis; substitution hormonal treatment with menopausal disorders in the post-menopausal period, including vasomotor symptoms (increased sweating, hot flashes), depression, sleep disturbance, irritability, involutional changes in the genitourinary tract and skin in women with an unremoved uterus; contraception; contraception and treatment of severe premenstrual syndrome; contraception and treatment of moderate acne); contraception in women with folate deficiency; contraception for women with symptoms of hormone-dependent fluid retention in the body.
Dosing and Administration of Drospirenone
The method of administration and doses are set individually by the doctor, depending on the indications and the dosage form used.
Contraindications for use
Hypersensitivity, porphyria, tendency to thrombosis, pronounced violations of the functional state of the liver, acute forms of thromboembolic diseases or phlebitis, vaginal bleeding of unknown origin, cancer of the breast and genital organs, pregnancy, breast-feeding.
Application restrictions
Pathology of the circulatory system, including arterial hypertension, severe violations of the functional state of the kidneys, bronchial asthma, diabetes mellitus, pathology of the central nervous system including depression, epilepsy, migraine.
Use during pregnancy and lactation
Drospirenone is contraindicated in pregnancy and lactation.
Side effects of drospirenone
Allergic reactions, thromboembolism (including cerebral and pulmonary arteries), retinal vein thrombosis, thrombophlebitis, dizziness, increased blood pressure, calculous cholecystitis, edema, cholestatic hepatitis, headache, drowsiness, depression, dysphoria, apathy, blurred vision, nausea, loss of appetite, vomiting, galactorrhea, changes in body weight, alopecia, hirsutism, enlargement, tension and pain in the mammary glands, menstrual disorders (intermittent bleeding, contraction), decreased libido , spotting, breakthrough uterine bleeding, a change in the nature of vaginal discharge, a condition similar to premenstrual syndrome, an increase in the size of fibroids, benign breast formations, skin itching, skin rash, chloasma, erythema multiforme, erythema nodosum, migraine, anxiety, fatigue, insomnia, palpitations, edema, varicose veins, muscle cramps, intolerance contact lenses.
Interaction of drospirenone with other substances
Long-term therapy with drugs that induce liver enzymes (including barbiturates, hydantoin derivatives, primidone, rifampicin, carbamazepine, oxcarbazepine, felbamate, topiramate, griseofulvin) may increase the clearance of sex hormones and reduce their effectiveness. Drospirenone may reduce the effectiveness of anabolic steroids and drugs that stimulate uterine smooth muscle.
Overdose
With an overdose of drospirenone, nausea, vomiting, vaginal bleeding are possible. Necessary symptomatic treatment there is no antidote.
Trade names of drugs with the active substance drospirenone
Used in combined preparations:
Drospirenone + Estradiol: Angeliq®;
Drospirenone + Ethinylestradiol: Dailla®, Jess®, Midiana®, Yarina®;
Drospirenone + Ethinylestradiol + [Calcium levometholinate]: Jess® Plus, Yarina® Plus;
Ethinylestradiol + Drospirenone: Dimia®, Yarina®.
To protect against unwanted pregnancy, there are many types of contraceptives. They come in different groups and compositions, also have different dosage and acceptance rules. The active ingredient in many drugs is drospirenone. What is this hormone? All the necessary information can be found in the article.
Properties
Drospirenone belongs to the hormonal group of substances. These are estrogens, gestagens. The agent is a derivative of spirinolactone. This hormone has a therapeutic effect in androgen-dependent diseases such as seborrhea, acne. Drospirenone also helps to remove excess fluid and sodium ions from the body, which provoke an increase in body weight, increased pressure, and swelling of the mammary gland.
In general, all those unpleasant conditions that are observed in the premenstrual period can be eliminated by the hormone. Therefore, women who take drospirenone-based drugs rarely suffer from PMS. When ingested, the substance is rapidly absorbed. Do all women need drospirenone? What is this hormone? And endometriosis, and menstrual irregularities - with all these disorders, hormonal treatment is indicated.
Where else is drospirenone used?
The hormone is prescribed for the combined treatment of osteoporosis in the postmenopausal period. The substance is used as replacement therapy with all the symptoms of postmenopausal syndrome, which are accompanied by increased sweating, fever.
The remedy copes well with sleep disturbance, depression, irritability in women before menstruation and at the beginning of menopause. In pharmacies you can find the drug "Drospirenone" (suppresses ovulation). This remedy is widely used to prevent pregnancy. The hormone is prescribed by a doctor on an individual basis. It is not recommended to use drugs based on drospirenone on your own.
Contraindications
You can not prescribe this hormone with hypersensitivity. Also with thrombosis, vaginal bleeding of unknown etiology, thromboembolism. It is forbidden to take during pregnancy and lactation, with cancer of the female genital organs and breast. With caution, you need to prescribe a remedy for circulatory disorders, high blood pressure, bronchial asthma, diabetes mellitus.
Do not use in case of pathology of the liver, central nervous system, which are accompanied by depression, epilepsy. Drospirenone - what is this hormone? Why not take it uncontrollably? Experts say that unpleasant symptoms can develop.
Side effects
The hormone can cause an allergic reaction, which is manifested by a rash and itching of the skin. The substance may cause dizziness, headache, thromboembolism, increased pressure, blurred vision, vomiting, nausea, stomach pain, diarrhea. can lead to such unpleasant consequences as a change in body weight, sleep disturbance, apathy.
On the part of the reproductive system, there are violations of the menstrual cycle, intermediate bleeding, enlargement of the mammary glands. There may be benign tumors in the breast and uterus, a change in the index of the vaginal smear, an increase in fibroids. V rare cases there is intolerance to contact lenses, swelling, increased heart rate, thrombophlebitis. Drospirenone suppresses ovulation. Women who are planning a pregnancy should avoid hormone-based drugs.
If we consider contraceptives with drospirenone, the most popular is Yarina. The features of its use will be described below.
The drug "Yarina"
It is monophasic which has antiandrogenic properties. Available in the form of yellow tablets. The composition of the drug includes drospirenone and enilestradiol. Produced in blister packs.
The main effect of the drug is based on the suppression of ovulation and an increase in viscosity. In women taking a combined contraceptive, menstruation normalizes, pain decreases, bleeding becomes less pronounced, which reduces the risk of anemia. After many studies, scientists announced that the hormone, which is part of birth control pills prevents the development of ovarian and endometrial cancer. Drospirenone prevents the formation of edema, increased pressure and The indication for taking the pills is contraception.
You can not prescribe the drug for thrombosis in the acute and chronic period. If there is a history of migraine, diabetes mellitus, the risk of venous and arterial thrombosis, the medication is also not used.
The tablets must be taken daily. The medicine should be swallowed whole and washed down with a small amount of water. The appointment is for 21 days. Then you need to take a break of seven days and start drinking the medicine from another package. It is better to take the tablets at the same time of day.
Should I use drugs that include drospirenone?
What is this hormone, it was possible to figure it out. Its main purpose is to suppress ovulation. Therefore, the use of drugs is for those women who do not plan pregnancy. However, it is worth remembering that side effects has drospirenone. What contraceptives contain a hormone? Enough for many. Before using birth control pills, you should carefully study the instructions.
Russian name
Drospirenone + EstradiolLatin name of substances Drospirenone + Estradiol
Drospirenonum + Oestradiolum ( genus. Drospirenoni + Oestradioli)Pharmacological group of substances Drospirenone + Estradiol
Model clinical and pharmacological article 1
Pharma action. Combined estrogen-gestagenic drug. Estradiol in the human body turns into natural 17 beta-estradiol. Drospirenone is a spironolactone derivative with progestogenic, antigonadotropic and antiandrogenic, as well as antimineralocorticoid effects. Estradiol compensates for the deficiency of estrogen in the body after menopause and provides effective treatment psycho-emotional and vegetative menopausal symptoms (such as hot flashes, increased sweating, sleep disturbance, increased nervous irritability, irritability, palpitations, cardialgia, dizziness, headache, decreased libido, myalgia, arthralgia); involution of the skin and mucous membranes, especially the mucous membranes of the genitourinary system (urinary incontinence, dryness and irritation of the vaginal mucosa, dyspareunia). Prevents bone loss caused by estrogen deficiency, which is mainly associated with the suppression of osteoclast function and a shift in the process of bone remodeling towards bone formation. It has been proven that long-term use of HRT can reduce the risk of peripheral bone fractures in postmenopausal women. With the abolition of HRT, the rate of decrease in bone mass is comparable to that characteristic of the period immediately after menopause. It has not been proven that, using HRT, it is possible to restore bone mass to pre-menopausal levels. HRT also has a positive effect on the content of collagen in the skin, skin density, and slows down the formation of wrinkles. Due to the antiandrogenic properties of drospirenone, the drug has a therapeutic effect on androgen-dependent diseases such as acne, seborrhea, androgenetic alopecia. Drospirenone has antimineralocorticoid activity, increases the excretion of Na + and water, which can prevent an increase in blood pressure, body weight, edema, breast tenderness, and other symptoms associated with fluid retention. After 12 weeks of using the drug, there is a slight decrease in blood pressure (systolic - an average of 2-4 mm Hg, diastolic - 1-3 mm Hg). The effect on blood pressure is more pronounced in women with borderline arterial hypertension. After 12 months of using the drug, the average body weight remains unchanged or decreases by 1.1-1.2 kg. Drospirenone is devoid of androgenic, estrogenic, glucocorticosteroid and antiglucocorticosteroid activity, does not affect glucose tolerance and insulin resistance, which, in combination with antimineralocorticoid and antiandrogenic effects, provides drospirenone with a biochemical and pharmacological profile similar to natural progesterone. Taking the drug leads to a decrease in the concentration of total cholesterol and LDL, as well as a slight increase in the concentration of triglycerides. Drospirenone reduces the rise in triglycerides caused by estradiol. The addition of drospirenone prevents the development of hyperplasia and endometrial cancer. Observational studies suggest that among postmenopausal women, the use of HRT reduces the incidence of colon cancer. The mechanism of action is still unclear.
Pharmacokinetics. Estradiol: after oral administration, it is rapidly and completely absorbed. During absorption and "primary passage" through the liver, estradiol is largely metabolized (including estrone, estriol and estrone sulfate). Bioavailability - about 5%. Eating does not affect the bioavailability of estradiol. C max - 22 pg / ml, TC max - 6-8 hours. C ss of estradiol after repeated administration is approximately 2 times higher than after a single dose. On average, the concentration of estradiol in the blood serum is in the range of 20-43 pg / ml. After stopping the drug, the concentrations of estradiol and estrone return to their original values within 5 days. Estradiol binds to albumin and sex hormone-binding globulin (SHBG). The free fraction of estradiol in serum is approximately 1-12%, and the fraction of the substance associated with SHBG is 40-45%. The apparent volume of distribution is about 1 l / kg. It is metabolized mainly in the liver, and also partially in the intestines, kidneys, skeletal muscles and target organs with the formation of estrone, estriol, catechol estrogens, as well as sulfate and glucuronide conjugates of these compounds, which have significantly less estrogenic activity or are pharmacologically inactive. The clearance of estradiol is about 30 ml / min / kg. Estradiol metabolites are excreted in the urine and bile with T 1/2 - 24 hours. Drospirenone: after oral administration, it is rapidly and completely absorbed. Bioavailability - 76-85%. Eating does not affect bioavailability. Cmax - 22 ng / ml, TC max - 1 hour after single and multiple doses of 2 mg of drospirenone. After that, a two-phase decrease in serum concentration is observed with a final T 1/2 of about 35-39 hours. C ss is achieved after about 10 days of daily administration of the drug. Due to the long T 1/2 of drospirenone, C ss is 2-3 times higher than the concentration after a single dose. Drospirenone binds to serum albumin and does not bind to SHBG and corticoid-binding globulin. About 3-5% of drospirenone does not bind to proteins. The main metabolites are the acidic form of drospirenone and 4,5-dihydrodrospirenone-3-sulfate, which are formed without the participation of the cytochrome P450 system. Drospirenone clearance - 1.2-1.5 ml / min / kg. It is excreted mainly in the form of metabolites with urine and feces in a ratio of 1.2:1.4, with a T 1/2 of about 40 hours; a small part is displayed unchanged.
Indications. HRT for menopausal disorders in the post-menopausal period in women with an unremoved uterus. Prevention of postmenopausal osteoporosis.
Contraindications. Hypersensitivity, vaginal bleeding of unknown origin, established or suspected breast cancer, established or suspected hormone-dependent precancerous diseases or hormone-dependent malignant tumors, benign or malignant liver tumors (including history), serious illnesses liver, severe kidney disease, incl. in history (before normalization of renal function), acute arterial thrombosis or thromboembolism (including myocardial infarction, stroke), deep vein thrombosis in art. exacerbations, venous thromboembolism (including history), severe hypertriglyceridemia, pregnancy, lactation.
Carefully. Arterial hypertension, congenital hyperbilirubinemia (Gilbert, Dubin-Johnson and Rotor syndrome), cholestatic jaundice or cholestatic itching during pregnancy, endometriosis, uterine fibroids, diabetes mellitus.
Dosing. Inside, 1 tablet daily. The tablet is swallowed whole with a small amount of liquid. If a woman is not taking estrogen or is switching from another combination hormonal drug for continuous use, she can start treatment at any time. Patients who are switching from a combination drug for cyclic HRT should start taking the drug after the end of the "withdrawal" bleeding.
After finishing taking 28 tablets from the current package, the next day, start a new package, taking the first tablet on the same day of the week as the first tablet from the previous package.
The time of day when a woman takes the drug does not matter, however, if she started taking the pills at any particular time, she should stick to this time and beyond. The forgotten tablet should be taken as soon as possible. If more than 24 hours have passed since the usual time of administration, an additional tablet should not be taken. If several tablets are missed, vaginal bleeding may develop.
Side effect. On the part of the reproductive system: "breakthrough" uterine bleeding and spotting (usually stop during therapy), a change in the nature of vaginal discharge, an increase in the size of fibroids, a condition similar to premenstrual syndrome; soreness, tension and / or enlargement of the mammary glands, benign formations of the mammary glands.
From the side digestive system: dyspepsia, bloating, nausea, vomiting, abdominal pain, recurrence of cholestatic jaundice.
From the side skin: skin rash, pruritus, chloasma, erythema nodosum, erythema multiforme.
From the side of the central nervous system: headache, migraine, dizziness, emotional lability, anxiety, increased nervous excitability, increased fatigue, insomnia.
Others: rarely - palpitations, edema, increased blood pressure, varicose veins, superficial thrombophlebitis, venous thrombosis and thromboembolism, muscle cramps, changes in body weight, changes in libido, visual impairment, intolerance to contact lenses, allergic reactions.
Overdose. Acute toxicity studies have shown no risk of developing acute side effects in case of accidental administration of the drug in an amount many times higher than the daily therapeutic dose.
Symptoms (presumed): nausea, vomiting, vaginal bleeding.
Treatment: symptomatic, there is no specific antidote.
Interaction. Long term treatment Drugs that induce liver enzymes (including hydantoin derivatives, barbiturates, primidone, carbamazepine, rifampicin, oxcarbazepine, topiramate, felbamate, griseofulvin) can increase the clearance of sex hormones and reduce their clinical effectiveness. The maximum induction of enzymes is usually observed 2-3 weeks after the start of treatment and may persist for 4 weeks after discontinuation of the drug.
In rare cases, against the background of the concomitant use of certain antibiotics (including penicillin and tetracycline groups), a decrease in the concentration of estradiol was observed.
Drugs that are heavily conjugated (including paracetamol) can increase the bioavailability of estradiol due to competitive inhibition of the conjugation system during absorption.
Ethanol can increase the concentration of circulating estradiol.
Special instructions. Not used for contraception. If contraception is necessary, non-hormonal methods should be used (with the exception of calendar and temperature methods). If pregnancy is suspected, the drug should be discontinued until pregnancy has been ruled out.
A number of controlled, randomized, as well as epidemiological studies have revealed an increased relative risk of developing venous thromboembolism (including deep vein thrombosis or PE) against the background of HRT. Therefore, when prescribing HRT to women with risk factors for venous thromboembolism, the risks and benefits should be weighed and discussed with the patient.
Risk factors for the development of venous thromboembolism include individual and family history (the presence of venous thromboembolism in close relatives at a relatively young age may indicate a genetic predisposition) and severe obesity. The risk of venous thromboembolism also increases with age. Question about a possible role varicose veins veins in the development of venous thromboembolism remains controversial.
The risk of venous thromboembolism may temporarily increase with prolonged immobilization, extensive elective, traumatological operations, or massive trauma. Depending on the cause or duration of immobilization, the question of the advisability of temporarily stopping HRT should be decided.
Treatment should be stopped immediately if symptoms of thrombotic disorders appear or if they are suspected.
In the course of randomized controlled trials with long-term use of combined conjugated estrogens and medroxyprogesterone, there was no evidence of a positive effect on the cardiovascular system. An increased risk of stroke has also been found. To date, there have been no long-term randomized controlled trials with other drugs for HRT in order to identify a positive effect on morbidity and mortality rates related to CVS. Therefore, it is not known whether the increased risk extends to HRT preparations containing other types of estrogens and progestogens.
With prolonged estrogen monotherapy, the risk of developing endometrial hyperplasia or carcinoma increases. Studies have confirmed that the combination with gestagens reduces the risk of hyperplasia and endometrial cancer. According to clinical studies and observational studies, an increased risk of developing breast cancer was found in women using HRT for several years. This may be due to earlier diagnosis, the biological effects of HRT, or a combination of both. The relative risk increases with the duration of treatment (by 2.3% for 1 year of use). This is comparable to an increase in the risk of breast cancer in women with each year of delay in the onset of natural menopause (by 2.8% for 1 year of delay). The increased risk gradually decreases to normal levels during the first 5 years after stopping HRT. Breast cancer found in women taking HRT is usually more localized than in women not taking it.
HRT increases mammographic density of the mammary glands, which in some cases can have a negative impact on the radiological detection of breast cancer.
Against the background of the use of sex hormones, in rare cases, benign, and even more rarely, malignant tumors of the liver were observed, in some cases with life-threatening intra-abdominal bleeding. With the appearance of pain in the upper abdomen, enlargement of the liver or signs of intra-abdominal bleeding with differential diagnosis consideration should be given to the possibility of a liver tumor.
It has been established that estrogens increase the lithogenicity of bile, which increases the risk of developing cholelithiasis in predisposed patients.
Treatment should be stopped immediately when migraine-like or frequent and unusually severe headaches appear for the first time, as well as when other symptoms appear - possible precursors of cerebral thrombotic stroke.
The relationship between HRT and the development of clinically significant arterial hypertension not installed. In women taking HRT, a slight increase in blood pressure has been described, a clinically significant increase is rare. However, in some cases, with the development of persistent clinically significant arterial hypertension while taking HRT, it is necessary to consider the abolition of HRT.
In renal insufficiency, the ability to excrete K + may decrease. Drospirenone does not affect the serum K + concentration in patients with mild to moderate renal insufficiency. The risk of developing hyperkalemia cannot theoretically be excluded in the group of patients in whom the concentration of K + in serum before treatment was determined on upper bound norms, and who additionally take potassium-sparing drugs.
With mild violations of liver function, incl. various forms of hyperbilirubinemia (Dubin-Johnson syndrome, Rotor), medical supervision is necessary, as well as periodic studies of liver function. If liver function tests deteriorate, HRT should be discontinued.
In case of recurrence of cholestatic jaundice or cholestatic pruritus, observed for the first time during pregnancy or previous treatment with sex hormones, HRT should be stopped immediately.
Special monitoring is required for women with moderate hypertriglyceridemia. In such cases, the use of HRT can cause a further increase in the concentration of triglycerides in the blood, which increases the risk of developing acute pancreatitis.
Although HRT may affect peripheral insulin resistance and glucose tolerance, the need to change the treatment regimen of patients diabetes during HRT, usually does not occur. However, diabetic women should be supervised during HRT.
Some patients under the influence of HRT may develop undesirable manifestations of estrogen stimulation, incl. pathological uterine bleeding. Frequent or persistent abnormal uterine bleeding during treatment is an indication for endometrial examination.
If the treatment of irregular menstrual cycles does not work, an examination should be carried out to rule out an organic disease.
Under the influence of estrogens, uterine fibroids can increase in size. In this case, treatment should be discontinued.
If a prolactinoma is suspected, this disease should be excluded before starting treatment.
In some cases, chloasma may occur, especially in women with a history of chloasma of pregnancy. During HRT, women with a tendency to develop chloasma should avoid prolonged exposure to the sun or UV radiation.
The following conditions may occur or worsen on the background of HRT (the relationship with HRT has not been proven): epilepsy, benign breast tumors, bronchial asthma, migraine, porphyria, otosclerosis, systemic lupus erythematosus, chorea minor.
Before starting or resuming HRT, a woman is recommended to undergo a thorough general medical and gynecological examination (including examination of the mammary glands and cytological examination cervical mucus), exclude pregnancy. In addition, violations of the blood coagulation system should be excluded. Control examinations should be carried out periodically.
Reception of sex hormones can affect the biochemical parameters of liver function, thyroid gland, adrenal glands and kidneys, on the content of transport proteins in plasma, such as SHBG and lipid / lipoprotein fractions, indicators carbohydrate metabolism, coagulation and fibrinolysis. The drug does not adversely affect glucose tolerance.
HRT is not prescribed during pregnancy or breastfeeding. Large-scale epidemiological studies of sex hormones used for contraception or HRT have not found an increased risk of birth defects in children born to women who took such hormones before pregnancy
State register of medicines. Official publication: in 2 volumes - M .: Medical Council, 2009. - V.2, part 1 - 568 p.; part 2 - 560 p.
APPROVED
By order of the chairman
Medical and
pharmaceutical activities
Ministry of Health and
social development
Republic of Kazakhstan
From "___" ___________ 201__
Instructions for medical use
medicinal product
Tradename
International non-proprietary name
Dosage form
Film-coated tablets, 3 mg/0.03 mg
Compound
One tablet contains
active substances: drospirenone 3 mg, ethinyl estradiol 0.03 mg,
Excipients: lactose monohydrate, corn starch, pregelatinized starch, crospovidone (type B), crospovidone (type A), povidone K-30, polysorbate 80, magnesium stearate
Shell: Opadry ® II Yellow: macrogol 3350, polyvinyl alcohol, titanium dioxide (E171), talc, iron oxide yellow (E172)
Description
Round, film-coated yellow tablets.
Pharmacotherapeutic group
Sex hormones and modulators of the reproductive system. Hormonal contraceptives for systemic use. Progestogens and estrogens (fixed combinations). Drospirenone and estrogen
ATX code G03AA12
Pharmacokinetics
Drospirenone
Absorption
When taken orally, drospirenone is rapidly and almost completely absorbed. After a single oral administration, the maximum serum concentration of drospirenone, equal to 38 ng / ml, is reached after 1-2 hours. Bioavailability ranges from 76 to 85%. Eating does not affect the bioavailability of drospirenone.
Distribution
Drospirenone binds to serum albumin and does not bind to sex hormone-binding globulin (SHBG) or corticosteroid-binding globulin (CBG). Only 3-5% of the total serum level of the hormone is in free form, 95-97% is specifically associated with SHPS. The increase in SHBG levels induced by ethinylestradiol does not affect the binding of drospirenone to plasma proteins. The average apparent volume of distribution is approximately 3.7±1.2 l/kg.
Metabolism
After oral intake drospirenone is completely metabolized. Most of the metabolites in plasma are represented by acidic forms of drospirenone, derivatives with an open lactone ring, and 4,5-dihydro-drosperinone-3-sulfate, which are formed without the involvement of the P450 system.
According to in vitro studies, drospirenone is metabolized in small quantities with the participation of cytochrome P450 3A4.
The serum clearance rate is approximately 1.5±0.2 ml/min/kg.
Elimination
Equilibrium concentration
The pharmacokinetics of drospirenone is not affected by the level of SHBG in the blood serum. As a result of daily intake of the drug, the level of substances in the serum increases by about two to four times, and the equilibrium concentration is reached in the second half of the course.
Ethinylestradiol
Absorption
After oral administration, ethinylestradiol is absorbed rapidly and completely. The maximum concentration in blood plasma, equal to approximately 30-100 ng / ml, is reached in 1-2 hours. During absorption and the first passage through the liver, ethinylestradiol is extensively metabolized, resulting in an average oral bioavailability of about 45%.
Distribution
Ethinylestradiol is almost completely (98%) bound by albumin. Ethinylestradiol induces the synthesis of SHPS. The apparent volume of distribution of ethinylestradiol is 5 l/kg.
Metabolism
Ethinylestradiol undergoes presystemic conjugation in the mucosa small intestine and in the liver, it is primarily metabolized by aromatic hydroxylation, with the formation of various hydroxylated and methylated metabolites, presented both in the form of free metabolites and in the form of conjugates with glucuronic and sulfuric acids. The rate of metabolic clearance of ethinyl estradiol is approximately 5 ml/min/kg.
Elimination
Equilibrium concentration
Equilibrium concentration is reached approximately in the second half of the treatment cycle.
Pharmacodynamics
Innara is a low-dose monophasic oral contraceptive with antimineralocorticoid and antiandrogenic effects.
The contraceptive effect of Innara is based on the interaction of various factors, the most important of which are the inhibition of ovulation and changes in the viscosity of cervical mucus. In addition to the contraceptive effect, combined oral contraceptives have a positive effect, which should be considered when choosing a method of birth control. The cycle becomes more regular, painful periods are less often observed, the intensity of bleeding decreases, as a result of which the risk of iron deficiency anemia decreases.
The drospirenone contained in Innara has antimineralocorticoid activity, which can prevent weight gain and other symptoms associated with fluid retention, prevent estrogen-induced sodium retention, provide very good tolerance and have a positive effect on premenstrual syndrome. In combination with ethinyl estradiol, drospirenone improves the lipid profile and increases high-density lipoprotein (HDL) levels. Drospirenone has antiandrogenic activity, which leads to a decrease in the manifestations of acne and a decrease in the production of sebaceous glands.
Drospirenone does not counteract the ethinylestradiol-induced increase in sex hormone-binding globulin (SHBG), which is useful for binding and inactivating endogenous androgens.
Drospirenone is devoid of any androgenic, estrogenic, glucocorticoid and antiglucocorticoid activity. This, in combination with antimineralocorticoid and antiandrogenic effects, provides drospirenone with a biochemical and pharmacological effect similar to the natural hormone progesterone. There is also evidence of a reduced risk of endometrial and ovarian cancer. High-dose oral contraceptives (0.05 mg ethinyl estradiol) reduce the incidence of ovarian cysts, pelvic inflammatory disease, benign breast disease, and ectopic pregnancy.
Indications for use
oral contraception
Dosage and administration
Combined oral contraceptives, including Innara, have a high contraceptive reliability. The "method failure" rate is no more than 1% per year. Contraceptive reliability may be reduced when pills are missed or taken incorrectly.
The tablets should be taken orally in the order indicated on the package, every day at about the same time with a little water. Take one tablet per day continuously for 21 days. Reception of each next package begins after a 7-day break, during which menstrual-like bleeding is observed. It usually starts 2-3 days after the last pill and may not end before the start of a new pack.
How to start taking Innara
In the absence of taking any hormonal contraceptives in the previous month
Innara is started on the first day of the menstrual cycle (i.e. the first day of menstrual bleeding). It is allowed to start taking on the 2nd-5th day 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 combined hormonal contraceptives (combined oral contraceptive, vaginal ring, transdermal patch)
It is preferable to start taking Innara the day after taking the last hormone-containing tablet from the previous pack, but in no case later than the next day after the usual 7-day break in intake (for preparations containing 21 tablets) or after taking the last hormone-free tablet (for preparations containing 28 tablets per package). When switching from a vaginal ring or transdermal patch, it is preferable to start taking Innara on the day the ring or patch is removed, but in no case later than the day when the next ring or patch should have been applied.
When switching from contraceptives containing only gestagens ("mini-pill", injectable forms, implant)
You can switch from a mini-pill to Innara any day (without a break), from an implant - on the day of its removal, from an injection form - from the day when the next injection should have been made. In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the tablets.
After an abortion in the first trimester of pregnancy
You can start taking it immediately, subject to this condition, there is no need for additional contraceptive protection.
After childbirth or abortion in the second trimester of pregnancy
It is recommended to start taking the drug on the 21-28th day after childbirth or abortion in the second trimester of pregnancy. If the reception is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the tablets. However, if a woman has already lived a sexual life, pregnancy should be excluded before taking the drug Innara, or it is necessary to wait for the first menstruation.
Taking missed pills
If the delay in taking the pill was less than 12 hours, contraceptive protection is not reduced, it is necessary to take the pill as soon as possible, the next one is taken at the usual time.
If the delay in taking the tablets was more than 12 hours, contraceptive protection may be reduced. In this case, you can be guided by the following two basic rules:
The drug should never be interrupted for more than 7 days.
7 days of continuous tablet intake are required to achieve adequate suppression of the hypothalamic-pituitary-ovarian system.
Accordingly, the following advice can be given if the delay in taking the tablets was more than 12 hours (the interval from the moment of taking the last tablet is more than 36 hours):
First week of taking the drug
The woman should take the last missed tablet as soon as she remembers (even if it means taking two tablets at the same time). The next tablet is taken at the usual time. Additionally, a barrier method of contraception (such as a condom) must be used for the next 7 days. If sexual intercourse took place within a week before missing the pills, the possibility of pregnancy should be considered.
As the number of missed pills increases and the regular break period approaches, the chance of pregnancy increases.
Second week of taking the drug
The woman should take the last missed tablet as soon as she remembers (even if it means taking two tablets at the same time). The next tablet is taken at the usual time.
If the woman has taken the pills correctly in the 7 days preceding the first missed pill, there is no need to use 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.
Third week of taking the drug
The risk of reduced reliability is inevitable due to the upcoming break in taking pills.
A woman must strictly adhere to one of the two following options.
1. Take the last missed pill as soon as possible (even if it means taking two pills at the same time). The next tablet is taken at the usual time until the tablets from the current package run out. The next pack should be started immediately. Withdrawal bleeding is unlikely until the second pack is finished, but spotting and breakthrough bleeding may occur while taking the tablets.
2. You can also stop taking the tablets from the current package. Then she should take a break for 7 days, including the day she skipped pills, and then start taking a new pack.
There is no need to use additional contraceptive measures if the drug was taken correctly in the previous 7 days before missing the pills.
If a woman misses taking the pills, and then during the 7-day break in taking the pills, menstrual-like bleeding was not observed, the presence of pregnancy should be excluded.
Tips for gastrointestinal disorders
In severe gastrointestinal disorders, the absorption of the drug may be incomplete. In this case, additional contraceptive measures should be taken. If a woman vomits within 3-4 hours after taking the tablets of the drug Innara, which may be tantamount to skipping the pills, you should focus on the advice regarding skipping the pills. If a woman does not want to change her normal drug regimen, she should take an additional tablet (or several tablets from another package) if necessary.
Changing the start date of the menstrual cycle
To delay the day of the onset of menstruation, it is necessary to continue taking the pill from the new package of the drug Innara immediately after taking all the pills from the previous one, without interrupting the intake. The pills in this new pack can be taken for as long as the woman wishes (as long as the pack runs out). While taking the drug from the second package, a woman may experience spotting or breakthrough uterine bleeding. Innara should be restarted from a new pack after the usual 7-day break.
To transfer the day of the onset of menstruation to another day of the week, the next break in taking the pills should be shortened by as many days as it is necessary to postpone the onset of menstruation. The shorter the interval, the higher the risk of not having withdrawal bleeding and, later on, spotting. spotting and breakthrough bleeding during the second pack (as well as when a woman wishes to delay the onset of menstruation).
Side effects
Often (1/100, 1/10):
Emotional lability, depression, decreased mood
Nausea
Migraine
Decrease or loss of libido
Breast pain, irregular uterine bleeding, unspecified bleeding from the genital tract
Rarely (1/10 000, 1/1000):
Venous or arterial thromboembolic processes (with a frequency, as with other oral contraceptives, including peripheral deep vein occlusion, thrombosis and embolism / occlusion of pulmonary vessels, myocardial infarction, non-hemorrhagic cerebral stroke).
With an unknown frequency (identified in the process of post-marketing observations)
Erythema multiforme
For a specific adverse reaction or its synonym or comorbid condition, the most appropriate term from the MedDRA-Medical Dictionary for Regulatory Activities (Version 12.1) is given.
Description of individual adverse reactions
Adverse reactions with a very low frequency or with a delayed onset of symptoms, which are considered as possibly interconnected with drugs of the group of combined oral contraceptives, are listed below:
The frequency of breast cancer diagnosis is slightly increased among women taking oral contraceptives. Since breast cancer is rare in women under 40 years of age, the increase in the number of diagnoses is insignificant in relation to the overall risk of developing this disease, and its relationship with the use of combined oral contraceptives has not been proven.
Liver tumors (benign and malignant)
Other states
erythema nodosum
Women with hypertriglyceridemia have an increased risk of pancreatitis when using combined oral contraceptives
Arterial hypertension
The appearance or worsening of conditions for which the relationship with the use of combined oral contraceptives has not been proven: jaundice and / or itching associated with cholestasis; the formation of stones in gallbladder; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; chorea; herpes of pregnant women; hearing loss associated with otosclerosis
In women with hereditary angioedema, exogenous estrogens may provoke or exacerbate the symptoms of this disease.
Liver dysfunction
Changes in glucose tolerance or effects of peripheral insulin resistance
Crohn's disease and ulcerative colitis
Chloasma
Hypersensitivity reactions (including symptoms such as rash and hives)
Contraindications
Combined oral contraceptives should not be used in the presence of any of the conditions listed below. If any of these conditions develop for the first time while taking the drug, the drug should be immediately discontinued.
Hypersensitivity to any of the components of the drug
Current or previous thrombosis/embolism (venous and arterial) (eg, deep vein thrombosis, pulmonary embolism, myocardial infarction) or cerebrovascular disease
Conditions preceding thrombosis (eg, transient ischemic attacks, angina pectoris) currently or in history
High risk of developing venous or arterial thrombosis
Migraine with a history of focal neurological symptoms
Diabetes mellitus with vascular complications
Severe liver disease (before normalization of liver tests)
Severe renal failure or acute renal failure
Liver tumors (benign or malignant) at present or in history
Identified or suspected hormone-dependent malignant diseases (for example, genital or mammary glands)
Unexplained vaginal bleeding
Pregnancy or suspicion of it
lactation period
Drug Interactions
Effects of other drugs on Innara
Interaction with drugs that induce liver enzymes is possible, which may contribute to an increase in the clearance of sex hormones and lead to breakthrough bleeding and / or a decrease in the contraceptive effectiveness of the drug.
While taking these drugs, a woman should additionally use a barrier method of contraception in addition to Innara, or choose another method of contraception. In this case, the barrier method of contraception should be used during the period of concomitant use of drugs and within 28 days after their withdrawal.
If the period of using the barrier method of protection ends later than the tablets in the package, you need to move on to the next package of the drug Innara without the usual break in taking the tablets.
Substances that increase the clearance of sex hormones (reduce the effectiveness of combined hormonal contraceptives due to the induction of liver enzymes), for example:
Phenytoin, barbiturates, primidone, carbamazepine and rifampicin; there are also suggestions for oxcarbazepine, topiramate, felbamate, griseofulvin and preparations containing St. John's wort.
Substances with different effects on the clearance of combined oral contraceptives
When combined with combined oral contraceptives, many HIV / HCV protease inhibitors and non-nucleoside reverse transcriptase inhibitors can increase or decrease plasma concentrations of estrogens or progestins. These changes may in some cases be relevant.
Substances that reduce the clearance of combined oral contraceptives (enzyme inhibitors)
Strong and moderate CYP3A4 inhibitors such as antifungals (eg, itraconazole, voriconazole, fluconazole), verapamil, macrolides (eg, clarithromycin, erythromycin), diltiazem, and grapefruit juice may increase plasma concentrations of estrogen or progestin, or both.
Etoricoxib at a dose of 60 to 120 mg / day increases the concentration of ethinylestradiol in plasma by 1.4-1.6 times when taken simultaneously with combined hormonal contraceptives containing 0.035 mg of ethinylestradiol.
Effect of combined oral contraceptives on other drugs
Combined oral contraceptives may interfere with the metabolism of certain other drugs, leading to an increase (eg, cyclosporine) or a decrease (eg, lamotrigine) in plasma and tissue concentrations.
Based on the results of in vivo interaction studies in volunteer participants using omeprazole, simvastatin or midazolam as marker substrates, a clinically significant effect of drospirenone at a dose of 3 mg on the metabolism of other drugs mediated by the cytochrome P450 system is unlikely.
In clinical studies, the administration of hormonal contraceptives containing ethinyl estradiol did not lead to any increase or even a slight increase in plasma concentrations of the CYP3A4 substrate (for example, midazolam), while the concentrations of the CYP1A2 substrate in the blood plasma may be slightly increased. (eg, theophylline) or moderate (eg, melatonin and tizanidine).
Other forms of interaction
There is a theoretical possibility of an increase in serum potassium levels in women receiving Innara tablets at the same time as other drugs that can increase serum potassium levels. These drugs are antagonists angiotensin-II receptors, potassium-sparing diuretics and aldosterone antagonists. However, when studying the interaction between drospirenone (in combination with estradiol) and an ACE inhibitor or indomethacin, no statistically significant changes in serum potassium levels were determined.
In addition to the above, when prescribing concomitant therapy, you should read the section drug interactions each of the prescribed drugs.
special instructions
Precautions and Warnings
If any of the conditions/risk factors listed below are currently present, then the potential risk and expected benefit of treatment with Innara should be carefully weighed in each individual case and discussed with the woman before she decides to start taking the drug. In the event of an increase or first manifestation of any of these conditions or risk factors, a decision should be made to discontinue the drug.
Diseases of the cardiovascular system
The results of epidemiological studies indicate a relationship between the use of combined oral contraceptives and an increased risk of developing venous and arterial thrombosis and thromboembolic processes, such as myocardial infarction, deep vein thrombosis, pulmonary embolism and cerebrovascular disorders. These diseases are rare.
The risk of developing venous thromboembolism (VTE) is highest in the first year of taking oral contraceptives. An increased risk is present after the initial use of combined oral contraceptives or the resumption of use of the same or different combined oral contraceptives (after a break between doses of 4 weeks or more). Data from a large prospective study in 3 groups of patients show that this increased risk is predominantly present during the first 3 months.
The overall risk of venous thromboembolism in patients taking oral contraceptives with a low dose of estrogens (less than 50 mcg ethinyl estradiol) is 2-3 times higher than in women not using them in the absence of pregnancy, however, this risk remains lower compared to with the risk of venous thromboembolism during pregnancy and childbirth.
Venous thromboembolism can be life-threatening or lead to lethal outcome in 1-2% of cases.
Venous thromboembolism, manifested as deep vein thrombosis and / or pulmonary embolism, can occur with the use of any combined oral contraceptives.
In women taking combined oral contraceptives, extremely rare cases of thrombosis of other blood vessels, such as hepatic, mesenteric, renal, cerebral arteries and veins, as well as retinal vessels, have been described.
Symptoms of deep vein thrombosis include the following: unilateral swelling in the leg or along a vein in the leg, pain or discomfort in the leg only when standing or walking, localized fever in the affected limb, redness or discoloration of the skin on the leg.
Symptoms of pulmonary embolism are as follows: the sudden onset of unexplained shortness of breath or rapid breathing, a sudden attack of coughing, which may be accompanied by hemoptysis, sharp pain v chest, which can be aggravated by deep breathing, anxiety, severe dizziness; fast or irregular heartbeat. Some of these symptoms (eg, "shortness of breath" and "cough") are nonspecific and may therefore be misinterpreted as signs of more frequent and less severe disorders (eg, respiratory tract infections).
Arterial thromboembolism may include cerebrovascular events, vascular occlusion, or myocardial infarction.
Symptoms of cerebrovascular disorders may include sudden weakness or numbness of the face, upper and lower extremities, especially on one side of the body, sudden confusion, impaired speech, or difficulty with perception; sudden blurred vision in one or both eyes, sudden trouble walking, dizziness, loss of balance or coordination, sudden severe or prolonged headache without apparent reason, loss of consciousness or fainting with or without a seizure. Other signs of vascular occlusion can also be sudden pain, swelling or slight cyanosis of the extremities, symptoms of "acute abdomen".
Symptoms of a myocardial infarction include: pain, discomfort, pressure, heaviness, a feeling of constriction or fullness in the chest, in the arm or behind the sternum, a feeling of discomfort radiating to the back, cheekbones, larynx, arm, stomach, a feeling of fullness or fullness in the stomach, a feeling of suffocation , cold sweat, nausea, vomiting or dizziness, severe weakness, anxiety, shortness of breath, rapid or irregular heartbeat.
Arterial thromboembolic processes can be life-threatening or fatal.
Consideration should be given to the possibility of an increased synergistic risk of thrombosis in women with a combination of several risk factors or a higher severity of one of the risk factors. In such cases, the increased risk may be greater than just the combined risk when all factors are considered.
Combined oral contraceptives should not be prescribed in case of a negative risk/benefit ratio (see section "Contraindications").
The risk of developing thrombosis (venous and / or arterial), thromboembolic or cerebrovascular disorders increases:
With age
Smokers (with an increase in the number of cigarettes or an increase in age, the risk further increases, especially in women over 35 years old)
If there is a family history (i.e. venous or arterial thromboembolism ever in close relatives or parents at a relatively young age). If a hereditary predisposition is known or suspected, a woman should consult a doctor to decide on the possibility of taking combined oral contraceptives
Obesity (body mass index over 30 kg/m2)
With dyslipoproteinemia
With arterial hypertension
For migraine
For valvular heart disease
With atrial fibrillation
With prolonged immobilization, major surgery, any operation on lower limbs or extensive trauma. In these situations, it is advisable to stop the use of combined oral contraceptives (in the case of a planned operation, at least four weeks before it) and not resume taking within two weeks after the end of immobilization.
The question of the possible role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism remains controversial. An increased risk of thromboembolism in the postpartum period should be taken into account.
Circulatory disorders can also occur in diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory diseases intestines (Crohn's disease or ulcerative colitis) and sickle cell anemia.
An increase in the frequency and severity of migraine during the use of combined oral contraceptives (which may precede cerebrovascular disorders) may be grounds for immediate discontinuation of these drugs.
Biochemical parameters that may be indicative of a hereditary or acquired predisposition to venous or arterial thrombosis include resistance to activated protein C, hyperhomocysteinemia, antithrombin-III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (cardiolipin antibodies, lupus anticoagulant).
In evaluating the risk/benefit ratio, the clinician should take into account that adequate treatment of the underlying condition may reduce the associated risk of thrombosis. It should also be borne in mind that the risk of thrombosis and thromboembolism during pregnancy is higher than when taking low-dose combined oral contraceptives (less than 0.05 mg of ethinyl estradiol).
The most important risk factor for developing cervical cancer is viral infection- persistent human papilloma (HPV). There are reports of some increased risk of cervical cancer with long-term use of combined oral contraceptives, but data remain conflicting about the extent to which this may be due to other factors, including cervical screening and sexual behavior, including the use of barrier devices. contraceptive methods.
A meta-analysis of 54 pharmaco-epidemiological studies demonstrated that there is a slightly increased relative risk (RR=1.24) of developing breast cancer diagnosed in women who were using combined oral contraceptives at the time of the study. The increased risk gradually disappears within 10 years after stopping these drugs. Due to the fact that breast cancer is rare in women under 40 years of age, the increase in the number of breast cancer diagnoses in women currently taking combined oral contraceptives or who have recently taken it is insignificant in relation to the overall risk of developing this disease. Its relationship with the use of combined oral contraceptives has not been proven. The observed increase in risk may be due to earlier diagnosis of breast cancer in women using combined oral contraceptives, the biological effects of combined oral contraceptives, or a combination of both factors. In women who have used combined oral contraceptives, clinically less pronounced breast cancer is detected than in women who have never used them.
In rare cases, against the background of the use of combined oral contraceptives, the development of benign tumors liver and, in even rarer cases, the development malignant tumors liver. In some cases, liver tumors can lead to life-threatening intra-abdominal bleeding. In the event of severe pain in the upper abdomen, liver enlargement, or signs of intra-abdominal bleeding, a liver tumor should be considered in the differential diagnosis.
Malignant tumors can be life-threatening or fatal.
Other states
In women with kidney failure potassium excretion may be slowed down. Clinical researches showed no effect of drospirenone on serum potassium concentration in patients with mild to moderate renal insufficiency. The theoretical risk of developing hyperkalemia can be assumed only in patients with impaired renal function with an initial concentration of potassium at the upper limit of the norm and in those who are simultaneously taking medicines leading to potassium retention in the body.
In women with hypertriglyceridemia (or a family history of this condition), there may be an increased risk of developing pancreatitis while taking combined oral contraceptives.
Although a slight increase in blood pressure has been described in many women taking combined oral contraceptives, clinically significant increases have been rare. However, if a persistent, clinically significant increase in blood pressure develops while taking combined oral contraceptives, these drugs should be discontinued and treatment of arterial hypertension should be initiated. Taking combined oral contraceptives can be continued if normal blood pressure values are achieved with antihypertensive therapy.
The following conditions observed during pregnancy may also appear or worsen when taking combined oral contraceptives: jaundice and / or itching associated with cholestasis; the formation of stones in the gallbladder; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; chorea; herpes of pregnant women; hearing loss associated with otosclerosis. However, the relationship between the development of these conditions and the use of combined oral contraceptives has not been proven.
In women with hereditary angioedema, exogenous estrogens may provoke or exacerbate the symptoms of this disease.
In the presence of acute or chronic violations of liver function, it is necessary to decide on the termination of the use of combined oral contraceptives, as long as the indicators of liver function are not normal. With the development of recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous use of sex hormones, you should stop taking combined oral contraceptives.
Although combined oral contraceptives may have an effect on insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetic patients using low-dose combined oral contraceptives (<0,05 мг этинилэстрадиола). Тем не менее, женщины с сахарным диабетом должны тщательно наблюдаться во время приема комбинированных пероральных контрацептивов.
Against the background of the use of combined oral contraceptives, manifestations of Crohn's disease and ulcerative colitis were observed.
Women with a tendency to chloasma while taking combined oral contraceptives should avoid prolonged exposure to the sun and exposure to ultraviolet radiation.
One tablet of Innara contains 62 mg of lactose monohydrate. In patients with rare hereditary disorders such as galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption who are on a lactose-free diet, the amount of lactose contained in Innara should be taken into account.
Medical examinations
Before starting the use of the drug Innara, as well as periodically in the process of using the drug, a woman is recommended to undergo a thorough general medical and gynecological examination (including measurement of blood pressure, examination of the mammary glands, abdominal organs and small pelvis, including a cytological examination of cervical mucus), exclude pregnancy. It is important to conduct periodic medical examinations, since contraindications (for example, transient ischemic attacks and others) or risk factors (for example, a hereditary predisposition to venous or arterial thrombosis) may occur during the use of the drug.
A woman should be warned that drugs such as Innara do not protect against HIV infection (AIDS) and other sexually transmitted diseases!
Reduced efficiency
The effectiveness of combined oral contraceptives may be reduced by missing pills, vomiting and diarrhea while taking pills, or as a result of drug interactions.
Effect on the menstrual cycle
While taking combined oral contraceptives, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of use. Therefore, evaluation of any irregular bleeding should be done only after an adaptation period of approximately three cycles.
If irregular bleeding recurs or develops after previous regular cycles, a thorough examination should be carried out to exclude malignant neoplasms or pregnancy.
Some women may not develop withdrawal bleeding during their pill break. If combined oral contraceptives were taken as directed, it is unlikely that the woman is pregnant. However, if combined oral contraceptives have been taken irregularly before, or if there are no consecutive withdrawal bleedings, pregnancy should be excluded before continuing the drug.
Laboratory tests
Taking combined oral contraceptives may affect the results of some laboratory tests, including biochemical parameters of liver, kidney, thyroid, adrenal function, plasma transport proteins, carbohydrate metabolism, coagulation and fibrinolysis parameters. Changes usually do not go beyond the boundaries of normal values. Drospirenone increases the activity of plasma renin and aldosterone, which is associated with its moderate antimineralocorticoid effect.
Innara is not prescribed during pregnancy. If pregnancy is detected while taking the drug, you should immediately stop taking it. However, extensive pharmaco-epidemiological studies have not revealed any increased risk of developmental defects in children born to women who received sex steroids (including combined oral contraceptives) before pregnancy or teratogenic effects when sex steroids were taken through negligence in early pregnancy.
Existing data on the results of taking Innara during pregnancy are limited, which does not allow drawing any conclusions about the effect of the drug on the course of pregnancy, the health of the fetus and newborn. There are currently no significant pharmaco-epidemiological data on Innara.
Taking combined oral contraceptives can reduce the amount of breast milk and change its composition, therefore, their use is generally not recommended until breastfeeding is stopped. Small amounts of sex steroids and/or their metabolites may be excreted in milk.
Do not use after the expiration date.
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