Symptoms: no severe toxic reactions are observed, nausea, vomiting (especially in young girls), bloody discharge/bleeding from the vagina may develop.
Treatment: symptomatic. There is no specific antidote. In rare cases, it is necessary to monitor the indicators of water-electrolyte metabolism and liver function.
Taking the drug Chariva® contraindicated in the following diseases/conditions:
hypersensitivity to the components of the drug,
the presence of thrombosis (venous and arterial) at the present time or in the anamnesis (for example, deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke),
the presence of the first signs of thrombosis, thrombophlebitis or symptoms of embolism (for example, transient ischemic attacks, angina, see " Special instructions»),
planned surgical intervention (at least 4 weeks before it) and the period of immobilization, for example, after an injury (including after applying plaster dressings),
diabetes mellitus with vascular complications,
diabetes mellitus that cannot be adequately controlled,
uncontrolled hypertension or a significant increase in blood pressure (above 140/90 mm Hg, see " Special instructions»),
hereditary or acquired predisposition to the development of venous or arterial thrombosis, such as increased resistance of the body to activated protein C (activated protein C resistance - ARS-resistance), antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant),
acute or chronic liver diseases of severe degree (before normalization of liver function indicators),
generalized itching, cholestasis, especially during a previous pregnancy or a history of taking sex hormones,
syndrome Dubin-Johnson syndrome Rotor, a violation of the outflow of bile,
the presence of liver tumors at present or in the anamnesis,
severe epigastric pain, enlarged liver, or symptoms of intra-abdominal bleeding,
first-time porphyria or its relapse (all three forms, especially acquired porphyria),
the presence of hormone-dependent malignant diseases, including in the anamnesis (for example, breast or uterus) or suspicion of them,
severe disorders of lipid metabolism,
pancreatitis currently or in anamnesis, in combination with severe forms of hypertriglyceridemia,
first-time migraine attacks or frequent severe headaches,
migraine in combination with local neurological symptoms (associated migraine),
acute sensory impairments, such as visual or hearing impairments,
motor disorders (in particular, paresis),
an increase in the number of epilepsy attacks,
severe depression,
worsening of the course of otosclerosis during previous pregnancies,
amenorrhea of unclear etiology,
endometrial hyperplasia,
vaginal bleeding of unknown etiology,
smoking over the age of 35 (see " Special instructions»),
lactose intolerance, lactase deficiency, glucose-galactose malabsorption,
the presence of pronounced or multiple factors of arterial or venous thrombosis (age increase, smoking, especially over the age of 35 years, obesity (<30 kg / m2), dyslipoproteinemia, the presence of a family history of venous or arterial insufficiency in relatives of the 1st line of kinship, heart valve diseases, atrial fibrillation, bacterial endocarditis, any operations on the lower extremities, extensive trauma).
pregnancy or suspected pregnancy,
breast-feeding period.
With caution: In the presence of the following conditions/diseases/risk factors, currently or in the anamnesis, the use of the drug Chariva® requires careful medical monitoring and assessment of the potential risk and expected benefit: epilepsy, multiple sclerosis, convulsive syndrome (tetany), migraine (without focal neurological symptoms), bronchial asthma, heart or kidney failure, chorea minor, diabetes mellitus with uncomplicated course, acute and chronic liver diseases of mild and moderate severity (with normal liver function tests), impaired lipid metabolism, dyslipoproteinemia (see also "Contraindications"), autoimmune diseases (including systemic lupus erythematosus), obesity (<30 kg/m2), controlled arterial hypertension, endometriosis, varicose veins, phlebitis of the superficial veins of the lower extremities (see also "Contraindications"), violation of the blood clotting system, mastopathy, uterine fibroids, herpes of pregnant women, depression (see also "Contraindications"), chronic inflammatory bowel diseases (Crohn's disease, ulcerative colitis).
Interaction of EE, the estrogenic component of the drug Chariva®, with other drugs may cause an increase or decrease in the concentration of ethinyl estradiol in the blood serum. If you need long-term treatment with these drugs, you should switch to non-hormonal contraceptives. A decrease in the concentration of EE in the blood serum can lead to an increase in episodes of breakthrough bleeding, cycle disruption and a decrease in the contraceptive effectiveness of the drug Chariva®. Increased serum EE concentrations may increase the frequency and severity of side effects.
The following drugs / active substances can reduce the concentration of EE in the blood serum:
- all drugs that enhance gastrointestinal motility (for example, metoclopramide) or interfere with absorption (for example, activated carbon),
- substances that induce microsomal liver enzymes, such as rifampicin, rifabutin, barbiturates, anticonvulsants (e.g. carbamazepine, phenytoin or topiramate), griseofulvin, roxaclon, primidone, modafinil, certain protease inhibitors (e.g. ritonavir) and St. John's wort preparations,
- some antibiotics (e.g. ampicillin, tetracycline) in selected women, possibly due to reduced intestinal-hepatic estrogen recycling.
With the simultaneous use of such drugs/active substances with the drug Chariva® it is necessary to use additional barrier methods of contraception, both during treatment and for 7 days after it. When taking active substances that reduce the concentration of EE in the blood plasma due to the induction of microsomal liver enzymes, additional barrier methods should be used within 28 days after the end of treatment.
If the concomitant medication should be continued after the end of the tablets in the package of the drug Chariva® then you should start taking the tablets from the next package, without taking the usual 7-day break.
The following drugs / active substances may increase the concentration of EE in the blood serum:
- active substances that inhibit the sulfation of EE in the intestinal wall (for example, ascorbic acid or paracetamol),
- atorvastatin (increases the EE AUC by 20%),
- active substances that inhibit the activity of microsomal liver enzymes, such as antifungal agents that are imidazole derivatives (for example, fluconazole), indinavir or troleandomycin.
EE can affect the metabolism of other substances:
- inhibit the activity of hepatic microsomal enzymes and, accordingly, increase the concentration in the blood serum of such active substances as diazepam (and other benzodiazepines, which are metabolized through hydroxylation), cyclosporine, theophylline and prednisone,
- induce glucuronidation in the liver and, accordingly, reduce the concentration in the blood serum of substances such as clofibrate, paracetamol, morphine and lorazepam.
Against the background of taking the drug Chariva® the need for insulin and oral hypoglycemic drugs may change, as the drug affects glucose tolerance.
This may also apply to medications that were taken shortly before taking the drug Chariva®.
Before prescribing any drug, you should study its brief characteristics to identify possible interactions with the drug Chariva®.
When taking the drug Chariva® the most common adverse reactions (>20% of cases) are breakthrough bleeding, vaginal bleeding, headache, and discomfort in the mammary glands. Intermenstrual bleeding usually decreases as the duration of taking the drug Chariva increases®.
The frequency of adverse reactions is determined as follows: very often - ≥1/10, often - ≥1/100, <1/10, infrequently - ≥1/1000, <1/100, rarely - ≥1/10 000, <1/1000, very rarely - <1/10 000.
There may be adverse reactions from the following organs and systems.
On the part of the immune system: infrequently-hypersensitivity to the components of the drug, including allergic reactions from the skin.
From the side of metabolism and nutrition: rarely-increased appetite.
Mental disorders: often-depressed mood, nervousness, irritability.
From the nervous system: often-dizziness, migraine (and / or its increase).
On the part of the visual organs: often-visual disorders, rarely-conjunctivitis, contact lens intolerance.
On the part of the organ of hearing and labyrinth disorders: rarely, sudden hearing loss, ringing in the ears.
From the CCC side: rarely-increased blood pressure, hypotension, cardiovascular collapse, varicose veins, venous thrombosis.
From the gastrointestinal tract: very often-nausea, often-vomiting, infrequently-abdominal pain, flatulence, diarrhea.
From the skin and subcutaneous tissues: often-acne, infrequently-pigmentation disorders, chloasma, hair loss, dry skin, rarely-urticaria, eczema, erythema, itching of the skin, increased psoriasis, hypertrichosis, very rarely-erythema nodosum.
Musculoskeletal and connective tissue disorders: often-a feeling of heaviness in the lower extremities, infrequently-back pain, muscle disorders.
From the genitals and breast: very often-increased vaginal discharge, painful menstrual-like spotting from the vagina, absence of menstrual-like spotting, often-pain in the lower abdomen, infrequently-galactorrhea, breast fibroadenoma, vaginal candidiasis, rarely-breast enlargement, vulvovaginitis, menorrhagia, premenstrual-like syndrome.
General disorders and disorders at the injection site: often-fatigue, swelling, weight gain, infrequently-decreased libido, hyperhidrosis, rarely-increased appetite.
Influence on the results of laboratory and instrumental examinations: infrequently-changes in the content of lipids in the blood plasma, including hypertriglyceridemia.
When using combined oral contraceptives (COC), including those containing 0.03 mg of EE and 2 mg of CMA, the following undesirable effects were also observed:
- increased risk of venous and arterial thromboembolism (for example, venous thrombosis, pulmonary embolism, stroke, myocardial infarction). The risk may be increased by additional factors (see " Special instructions»),
- increased risk of biliary tract diseases,
- in rare cases-an increased risk of developing benign liver neoplasms (and even less often - malignant liver neoplasms), isolated cases can lead to life-threatening intra-abdominal bleeding (see also " Special instructions»),
- exacerbation of chronic inflammatory bowel diseases (Crohn's disease, ulcerative colitis, see also "Special instructions").
Oral contraception.
Long-term use of the drug Chariva® leads to a decrease in the secretion of FSH and LH and, consequently, the suppression of ovulation. At the same time, endometrial proliferation and secretory transformation occur, which prevent the implantation of a fertilized egg, the viscosity of the mucous secretion of the cervix increases, which is accompanied by difficulty in passing spermatozoa through the cervical canal and a violation of their mobility.
For the complete suppression of ovulation requires 1.7 mg of chlormadinone acetate (CMA) on a daily basis. The required dose per cycle is 25 mg.
Part of the drug Chariva® CMA is a progestogen with antiandrogenic properties. Its action is based on the ability to replace androgens at specific receptors, eliminating and weakening the effect of endogenous and exogenous androgens. The Pearl index is equal to 0.291–0.698, depending on how carefully the woman follows the regimen of taking the drug.
HMA
Suction. When taking the drug inside, CMA is quickly and completely absorbed.
Tmax HMA — 1-2 hours.
Distribution. More than 95% of CMA binds to human plasma proteins, mainly albumin.
Metabolism. Various processes of reduction, oxidation and binding to glucuronides and sulfates lead to the formation of many metabolites. The main metabolites in blood plasma are 3-alpha and 3-beta-hydroxy-CMA with a half-life not significantly different from non-metabolized CMA. 3-hydroxy-metabolites have antiandrogenic activity similar to that of CMA itself. In the urine, the metabolites are mainly contained in the form of conjugates. After enzymatic cleavage, 2-alpha-hydroxy-CMA becomes the main metabolite, and 3-hydroxy-metabolites and dihydroxymetabolites are also formed.
Output. Average T1/2 CMA from the blood plasma is approximately 34 hours (after taking a single dose) and about 36-39 hours (with repeated use). When the drug is taken orally, CMA and its metabolites are excreted in approximately equal proportions by the kidneys and through the intestine.
Ethinyl estradiol (EE)
Suction. When taking the drug inside, EE is quickly and almost completely absorbed.
Tmax in the blood plasma is 1.5 hours.
Due to presystemic binding and liver metabolism, absolute bioavailability is about 40% and is subject to strong individual variability (20-65%).
Distribution. The data available in the literature on the concentration of EE in blood plasma vary greatly. About 98% of EE binds to plasma proteins, almost exclusively to albumin.
Metabolism. Like natural estrogens, EE is biotransformed through the hydroxylation of the aromatic ring (the mediator is the cytochrome P450 system). The main metabolite is 2-hydroxy-EE, which is transformed to other metabolites and conjugates. EE undergoes presystemic binding both in the mucosa of the small intestine and in the liver. In the urine, glucuronides are found mainly, and in bile and blood plasma — sulfates.
Output. Average T1/2 EE from the blood plasma is approximately 12-14 hours. EE is excreted by the kidneys and through the intestine in a ratio of 2:3. EE sulfate, which is excreted with bile after hydrolysis by intestinal bacteria, is subjected to intestinal-hepatic recirculation.
Chariva
Chlormadinone, Ethinyl Estradiol
Inside. Tablets marked with the appropriate day of the week should be removed from the blister pack and swallowed whole, if necessary, washed down with a small amount of water. One tablet should be taken every day at the same time (preferably in the evening) for 21 consecutive days, then a 7-day break should be taken, two to four days after taking the last tablet, withdrawal bleeding similar to menstrual bleeding will occur.
After the end of the 7-day break, you should start taking the drug Chariva® from the next pack, regardless of whether the bleeding has stopped or not.
Start taking pills
If hormonal contraceptives have not been used before (during the last menstrual cycle). The first pill should be taken on the first day of a woman's natural cycle, i.e. on the first day of the next menstrual bleeding. If the first pill is taken on the first day of menstrual bleeding, the contraceptive effect of the drug begins on the first day of administration and continues for a 7-day break in taking the pills.
The first pill can also be taken on the 2nd-5th day of menstrual bleeding, regardless of whether the bleeding has stopped or not. In this case, during the first seven days of admission, it is necessary to use additional barrier methods of contraception.
If menstrual bleeding has started more than five days ago, the woman should be advised to wait until the beginning of the next menstrual bleeding to start taking the drug Chariva®.
Switching from another hormonal contraceptive to taking the drug Chariva®
Switching from another combined oral contraceptive.
Transition from drugs containing 21 or 22 active tablets. You should finish taking all the tablets of the old package. The first tablet of the drug Chariva® it must be taken the next day. There should be no interruption in taking the pills, and the patient should not wait for the next menstrual cycle. Additional contraceptive measures are not required.
When switching from another drug containing 28 tablets: the first tablet of the drug Chariva® it should be taken the next day after taking the last active tablet from the package of the previous contraceptive drug containing 28 tablets (i.e. after taking 21 active tablets). There should be no interruption in taking the pills, and the patient should not wait for the next menstrual cycle. Additional contraceptive measures are not required.
The transition from products containing only progestogen (minipill). The first tablet of the drug Chariva® it should be taken the next day after taking the last tablet containing only gestagen. During the first seven days, it is necessary to use additional barrier methods of contraception.
Transition from hormonal injectable contraceptives or a contraceptive implant. Taking the drug Chariva® you can start on the day of the implant removal or on the day of the originally planned injection. During the first seven days, it is necessary to use additional barrier methods of contraception.
After a spontaneous or medical abortion in the first trimester of pregnancy. Taking the drug Chariva® you can start immediately after a spontaneous or medical abortion in the first trimester of pregnancy. In this case, there is no need to apply additional contraceptive measures.
After childbirth, spontaneous or medical abortion in the second trimester of pregnancy. Taking the drug Chariva® it is recommended to start on the 21st-28th day after delivery, if the woman is not breastfeeding, or after an abortion in the second trimester of pregnancy. In this case, there is no need to use additional barrier methods of contraception.
If the drug was started more than 28 days after delivery or abortion, then additional barrier methods of contraception should be used during the first seven days.
If a woman has already had sexual intercourse, then you should exclude the presence of pregnancy or wait for the beginning of the next menstrual cycle before starting taking the drug.
The period of breastfeeding. During breastfeeding, it is contraindicated to take the drug Chariva®.
After discontinuation of the drug Chariva®. After discontinuation of the drug Chariva® the current cycle can be extended by about one week.
Irregular pill intake. If the patient forgot to take the pill, but took it within the next 12 hours, no additional contraceptive measures are required. The patient should continue taking the drug as usual.
If the patient forgot to take the pill, but took it after 12 hours, contraceptive protection may be reduced. In the case of skipping the pill, you should act according to the following two basic rules:
1. Never stop taking pills for more than 7 days.
2. 7 days of continuous tablet administration is necessary to achieve adequate suppression of the regulation of the hypothalamic-pituitary-ovarian system.
The last missed tablet should be taken immediately, even if it means that you need to take 2 tablets.. at the same time. The following tablets should be taken as usual. During the next 7 days, it is necessary to additionally use barrier methods of contraception, such as condoms. If the pills were missed during the 1st week of the cycle, and within 7 days before the missed pills there was sexual intercourse (including a 7-day break in taking the pills), the probability of pregnancy should be considered. The more pills that were missed, and the closer they were to the usual pill break, the higher the chance of pregnancy.
Skipping tablets on the 2nd and 3rd week of taking the drug. You should immediately take the missed tablet, even if it means taking 2 tablets at the same time. The next pill is taken as usual. During the next seven days, you must use additional methods of contraception, such as condoms.
If your pack has less than 7 tab., immediately after taking the pill used the pack to start taking pills from a new package of the drug Chariva®, i.e. there should be no break between the two packages. It is likely that the usual withdrawal bleeding will not occur until the tablets from the second package run out, but while taking the tablets from the new package, breakthrough bleeding or spotting bloody discharge from the vagina may occur. If withdrawal bleeding does not occur after the end of taking the tablets from the second package, then a pregnancy test should be performed.
Recommendations for gastrointestinal disorders
If vomiting or severe diarrhea occurs within 4 hours after taking the pill, the absorption of the drug may be incomplete and the reliability of contraception cannot be guaranteed. In this case, you should follow the recommendations given in the section "Irregular pill intake» (see above). You should continue taking the drug Chariva®.
How to delay withdrawal bleeding
To delay the bleeding, the woman should continue taking the tablets from the next package of the drug Chariva® without taking a break. You can continue taking the tablets at will until you run out of tablets from the second package. While taking the tablets from the second package, minor spotting or breakthrough bleeding may occur. After the usual 7-day break in taking tablets, you should resume regular use of the drug Chariva®. To move the beginning of bleeding to another day of the week, different from the day of the beginning of bleeding according to the current scheme, a woman can be recommended to reduce the next 7-day break by the desired number of days. The shorter the pill break, the higher the likelihood of no withdrawal bleeding and breakthrough bleeding or minor spotting during the next pill package (as well as when delaying bleeding).
