Rigevidon: clear instructions for use. Rigevidon n21x3 coated tablets Contraindications for use
APPROVED
By order of the chairman
Pharmaceutical Control Committee
Ministry of Health
Republic of Kazakhstan
From "____" ______________200
№______________________
Instructions for medical use
medicinal product
RIGEVIDON®
Tradename
Rigevidon®
International non-proprietary name
Dosage form
Coated tablets
Compound
One film-coated tablet contains
active substances: ethinylestradiol 0.03 mg
Levonorgestrel 0.15 mg
Excipients:
Core: colloidal anhydrous silica, magnesium stearate, talc, corn starch, lactose monohydrate (33.0 mg)
Shell: sucrose, talc, calcium carbonate, titanium dioxide (E171), copovidone, macrogol 6000, anhydrous colloidal silicon dioxide, povidone K-30, carmellose sodium
Description
White, round biconvex film-coated tablets.
Pharmacotherapeutic group
Hormonal oral contraceptives. Progestogens and estrogens
ATC code G03A A07
Pharmacological properties
Pharmacokinetics
Levonorgestrel
Levonorgestrel is rapidly absorbed (full absorption time less than 4 hours). Bioavailability is almost one hundred percent, due to the lack of primary (first pass) selection. Most levonorgestrel binds to plasma proteins, mainly albumin and sex hormone-binding globulin (SHBG).
The half-life of levonorgestrel shows individual variability and varies from 8 to 30 hours. Levonorgestrel is excreted in the urine and feces in the form of metabolites (sulfate and glucuronide conjugates).
Ethinylestradiol
Ethinylestradiol is absorbed rapidly and almost completely. After oral administration, the bioavailability is about 38-48%.
Ethinylestradiol is almost completely bound to plasma proteins, mainly to albumins.
Ethinylestradiol is cleaved by presystemic conjugation. Passing through the intestinal wall (first phase of metabolism), it passes through hepatic conjugation (second phase of metabolism). The most important metabolites of the first phase of metabolism are 2-OH-ethinylestradiol and 2-methoxy-ethinylestradiol. Both ethinylestradiol and metabolites of the first phase are excreted in the form of conjugates (sulfates and glucuronides) into the bile and enter the hepato-intestinal circulation. The half-life is 26±6.8 hours. About 40% is excreted in the urine and about 60% in the feces.
Pharmacodynamics
Combined contraceptive drug, acts by inhibiting the action of gonadotropins. Although the drug's primary mechanism of action is to inhibit ovulation, it also causes other changes, including changes in the consistency of cervical mucus, which makes it difficult for sperm to pass into the uterine cavity, as well as changes in the endometrium, which reduces the likelihood of implantation.
Indications for use
oral contraception
Dosage and administration
One film-coated tablet per day, preferably at the same time of day.
If a woman has not taken a contraceptive in the previous cycle, and the doctor has not ordered otherwise, the first pill should be taken on the first day of menstruation and pills should be continued for 21 days. After this, it is necessary to withstand a seven-day break, during which menstrual-like bleeding occurs.
The next 21-day tablet cycle should be started after a 7-day break, on the eighth day, even if the bleeding has not stopped. Thus, each intake cycle begins on the same day of the week.
This mode of taking the drug (21 days of admission - 7 days of break) must be repeated. Protection of the drug against unwanted pregnancy continues during the seven-day break period.
In the event that a woman took a contraceptive in the previous cycle, the drug should be started after a 7-day break, on the eighth day.
When switching to Rigevidon from another contraceptive, you must use the above scheme.
Taking the drug after childbirth or after an abortion can be started no earlier than the first day of menstruation after the first two-phase cycle. The first biphasic cycle is usually shortened due to premature ovulation. If the drug is started already at the first spontaneous bleeding, the drug cannot successfully prevent premature ovulation, so protection is not reliable in the first two weeks of the cycle.
If the tablet was missed on time, the missed tablet should be taken within 12 hours. In this case, there is no need to use additional methods of contraception. The remaining tablets should be taken at the usual time. If more than 12 hours have passed, you must take the last missed tablet (missing the remaining missed tablets) and continue taking the drug as normal. In this case, additional methods of contraception (barrier methods, spermicides) must be used for the next 7 days.
Side effects
Nausea, vomiting, diarrhea
Fatigue, headache
Tension of the mammary glands
Change in body weight and libido
Depressed mood
Chloasma
Intermenstrual bleeding
Complaints when wearing contact lenses
Increased triglycerides, blood glucose, reduced glucose tolerance
Increase in blood pressure
Pulmonary embolism, thromboembolism, myocardial infarction, stroke, retinal thrombosis, mesenteric thrombosis, thrombosis of the pelvic organs, lower extremities, deep vein thrombophlebitis of the lower extremities, deep vein thrombophlebitis
Hepatitis, gallbladder disease, jaundice
Skin rash, hair loss
Change in vaginal secretion, vaginal candidiasis
Contraindications
Hypersensitivity to the components of the drug
Pregnancy, lactation
Severe liver disease, cholelithiasis, cholecystitis, liver tumors
Congenital hyperbilirubinemia (Gilbert, Dubin-Johnson and Rotor syndromes)
chronic colitis
Presence or history of severe cardiovascular and cerebrovascular changes, thromboembolism and predisposition to them, hypertension
Malignant tumors, especially breast or endometrial cancer
Violation of fat metabolism
Migraine
Diseases of the endocrine glands, diabetes mellitus
sickle cell anemia, chronic hemolytic anemia
Bleeding from the vagina of unknown etiology
Otosclerosis (which worsened in a previous pregnancy)
History of idiopathic jaundice of pregnant women, pruritus of pregnant women, herpes of pregnant women.
Drug Interactions
The drug should be used with caution with:
Ampicillin, rifampicin, chloramphenicol, neomycin, penicillin B, sulfonamides, tetracyclines, dihydroergotamine, tranquilizers, phenylbutazone
Anticoagulants, coumarin or indandione derivatives (it is necessary to re-determine the prothrombin time and, if necessary, change the dose of the anticoagulant)
Tricyclic antidepressants, maprotiline, beta-blockers (may increase their bioavailability and toxicity)
Oral antidiabetic agents, insulin (dosage adjustment of these agents may be necessary)
Bromocriptine (decreased effectiveness)
Hepatotoxic drugs, especially with dantrolene (the risk of hepatotoxicity increases, especially in women over 35 years of age).
special instructions
Before starting the course of taking the drug, it is necessary to undergo a general medical and gynecological examination. First of all, it is necessary to measure blood pressure, conduct a laboratory examination of urine for the presence of glucose, monitor liver function, examine the mammary glands and conduct a cytological analysis of a vaginal smear to rule out pregnancy.
Special care is required during the use of the drug in the presence of the following diseases: diabetes mellitus, heart disease of non-ischemic etiology, hypertension, impaired renal function, varicose veins, phlebitis, otosclerosis, multiple sclerosis, epilepsy, chorea minor, intermittent porphyria, latent tetany, asthma , benign tumor of the uterus, endometriosis or mastopathy.
During the period of use of the drug, it is necessary to undergo a medical examination approximately every 6 months.
After the transfer of viral hepatitis (after normalization of liver function), oral hormonal contraceptives can be used 6 months after the cure.
After prolonged use of oral hormonal contraceptives, a rarely benign, in very rare cases, a malignant liver tumor can form, which in some cases can lead to life-threatening bleeding in the abdominal cavity. If there is severe pain in the upper abdomen, an enlarged liver, or signs of intraperitoneal bleeding, a liver tumor may be suspected. In this case, you must stop taking the drug.
A large number of epidemiological studies have studied the incidence of ovarian, endometrial, cervical and breast cancer among women taking combined oral contraceptives. Studies have proven that combined oral contraceptives protect women from ovarian and endometrial cancer.
Some studies have found an increase in the incidence of cervical cancer among women who have taken combined oral contraceptives for a long time, but the results are mixed. In the formation of cervical cancer, sexual behavior and other factors take place, so the relationship between cervical cancer and the use of combined oral contraceptives is not unambiguous.
There has been an increase in the incidence of breast cancer among women younger than 35 years of age, and this risk increases with the duration of oral hormonal contraception. Despite this, the likelihood of developing breast cancer is small and this likelihood is reduced with the use of drugs with a low dose of hormones. This low risk is compared with the positive effects of combined oral contraceptives, including protection against ovarian and endometrial cancer.
In the absence of bleeding, pregnancy must be excluded.
In the presence of impaired liver function, it is necessary to undergo medical supervision every 2-3 months.
With the appearance of intermenstrual bleeding, the drug should be continued, since in most cases these bleeding stop spontaneously. If intermenstrual bleeding does not disappear or recurs, a medical examination should be carried out to exclude damage to the genital organs.
In case of vomiting or diarrhea, the drug should be continued, additionally using another, non-hormonal method of contraception.
Among women taking oral contraceptives containing estrogen, the risk of developing thromboembolic diseases (stroke, myocardial infarction, subarachnoid hemorrhage) may increase.
The use of any combined oral contraceptive drug increases the risk of venous thromboembolic disease. The risk of these diseases peaks in the first year of taking the drugs. This increased risk is less than the risk of venous thromboembolic disease found during pregnancy, which is 60 cases out of 100,000 pregnancies. 1-2% of these cases end in death.
The probability of occurrence of thromboembolic diseases when using oral contraceptives containing 30 mcg of ethinyl estradiol and levonorgestrel is 20 cases out of 100,000 women per year.
Certain factors increase the risk of thromboembolic disease (eg, smoking, obesity, varicose veins, cardiovascular disease, diabetes, migraine). Before starting a course of administration and in the presence of these factors, it is necessary to assess that the selected combined contraceptive is suitable for the woman.
The risk of thromboembolic diseases associated with the use of combined oral contraceptives,
Increases with age and worsens with smoking. Therefore, women over 35 are encouraged to completely stop smoking.
In the development of thromboembolic diseases, the presence of thromboembolic diseases at a young age and in a family history, as well as impaired hemostasis, plays a role.
The drug should be stopped immediately in the following cases:
In the case of a first-time or intensified migraine-like or unusually severe headache; with acute deterioration of visual acuity and loss of feelings; with suspected thrombosis or infarction
With a sharp increase in blood pressure; with the development of jaundice or hepatitis without jaundice; in case of generalized itching; with epilepsy or an increase in epileptic seizures
Store at temperatures between +15 °C and +25 °C.
Keep out of the reach of children!
Shelf life
Do not use the drug after the expiration date.
Terms of dispensing from pharmacies
On prescription
Manufacturer
OJSC "Gedeon Richter"
1103 Budapest, st. Djemrei, 19-21, Hungary
- Instructions for use Rigevidon 21+7
- Composition of Rigevidon 21+7
- Indications for Rigevidon 21+7
- Storage conditions of the drug Rigevidon 21+7
- Shelf life of the drug Rigevidon 21+7
Release form, composition and packaging
tab., cover shell, two types: 28 pcs. in a blister, 1 or 3 blisters in a box, including: tab. white color 30 mcg + 150 mcg: 21 pcs. in blister, tab. brown, 76.05 mg: 7 pcs. in blisterReg. No: 3994/99/04/09 dated 04/20/2009 - Canceled
Coated tablets , of two kinds.
White film-coated tablets, round, biconvex, about 6 mm in diameter (21 pieces in a blister).
Excipients: anhydrous colloidal silicon dioxide, magnesium stearate, talc, corn starch, lactose monohydrate.
Shell composition: carmellose sodium, povidone K30, anhydrous colloidal silicon dioxide, macrogol 6000, copovidone, titanium dioxide (E171), calcium carbonate, talc, sucrose.
Tablets, coated with a reddish-brown color, glossy, round, biconvex (7 pieces in a blister).
Excipients: anhydrous colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, povidone, talc, potato starch, corn starch, lactose monohydrate.
Shell composition: carmellose sodium, macrogol 6000, povidone, iron oxide red (E172), anhydrous colloidal silicon dioxide, copovidone, titanium dioxide (E171), calcium carbonate, talc, sucrose.
28 pcs. - blisters (1) - cardboard boxes.
28 pcs. - blisters (3) - cardboard boxes.
Description of the medicinal product RIGEVIDON 21+7 based on officially approved instructions for use of the drug and made in 2009. Date of update: 11/12/2009
Combined low-dose monophasic oral contraceptive drug containing progestogen and estrogen.
The contraceptive effect is based on the interaction of various factors, the main of which is the suppression of ovulation and changes in the consistency of cervical mucus.
The Pearl Index (number of pregnancies per 100 women per year) for combined low-dose monophasic oral contraceptives containing levonorgestrel 150 mcg and ethinyl estradiol 30 mcg is 0.1 (a method based on the contraceptive failure rate).
Levonorgestrel
Suspension
Levonorgestrel is rapidly and completely absorbed after oral administration of Rigevidon. Bioavailability is approximately 100%, levonorgestrel is not subject to first pass metabolism.
Distribution
Levonorgestrel is primarily bound to albumin and to sex hormone-binding globulin (SHBG) in plasma.
Metabolism
Metabolism occurs mainly by abstraction of the D4-3-oxo group and hydroxylation at positions 2 alpha, 1 beta and 16 beta, followed by conjugation. Most of the metabolites circulating in the blood are 3a, 5(3-tetrahydro-levonorgestrel) sulfates, while glucuronides are predominantly excreted. Some parent levonorgestrel also circulates in the blood as 17p-sulfate. explain the significant variation in levonorgestrel concentrations in different patients.
breeding
At steady state, the average T 1/2 of levonorgestrel is about 36 hours. Levonorgestrel and its metabolites are mainly excreted in the urine (40-68%) and approximately 16-48% in the feces.
Ethinylestradiol
Suction
Ethinylestradiol is rapidly and completely absorbed, Cmax in plasma is reached after 1.5 hours. Bioavailability is 60%.
Distribution
Ethinylestradiol is 98.8% bound to plasma proteins, mainly to albumin.
Metabolism
Ethinylestradiol undergoes presystemic conjugation, both in the mucous membrane of the small intestine and in the liver. Hydrolysis of direct ethinylestradiol conjugates by the intestinal flora leads to the formation of ethinylestradiol, which can be reabsorbed, i.e. undergoes enterohepatic recirculation. The main pathway of ethinylestradiol metabolism is hydroxylation with the participation of isoenzymes of the cytochrome P450 system, the main metabolites are 2-OH-ethinylestradiol and 2-methoxyethinylestradiol. 2-OH-ethinylestradiol is further converted into reactive metabolites.
breeding
T1 / 2 ethinylestradiol is about 29 hours (26-33 hours), plasma clearance varies between 10-30 l / h. Conjugates of ethinylestradiol and its metabolites are excreted in the urine and feces (ratio 1:
Tablets of the drug Rigevidon 21+7 should be taken in the order indicated on the package, every day at approximately the same time.
Daily for 21 days, take 1 tab. white. Then the drug should be continued with reddish-brown tablets for 7 days, during which, as a rule, bleeding occurs. Bleeding usually starts on the 2nd or 3rd day after starting the iron tablets and may continue after the start of the tablets from the next pack. You should continue taking the next package containing 21 white tablets, and then 7 reddish-brown tablets without interruption. Thus, each intake cycle begins on the same day of the week.
Start taking Rigevidon 21+7
Over the past month, hormonal contraceptives have not been used. Tablets should be started on the first day of the normal menstrual cycle (i.e. on the first day of the onset of menstruation). You can start taking the pills on days 2-5, but the first cycle of taking the pills during the first 7 days should additionally use a barrier method of contraception.
The composition of tablets of different colors is not the same. Therefore, the beginning and the correct sequence of administration - first 21 white tablets, then 7 reddish-brown tablets - are indicated on the packaging by numbers and arrows.
Switching from other combined hormonal contraceptives (combined oral contraceptive pills, vaginal ring, or transdermal patch): a woman can start taking Rigevidon the next day after taking the last pill from the previous pack of contraceptive pills (or after the vaginal ring or transdermal patch has been removed), but no later than the next day after the usual break (or taking placebo pills, or when the patch or ring has been removed) while using a previous contraceptive.
Moving away from a progesterone-only method (progesterone-only pills or "mini-pills," injections, implants). You can switch from taking progesterone-only pills at any time (if using an implant on the day the implant is removed, if using an injectable method of contraception on the day the next injection was due). In all cases, a woman should be advised to additionally use a barrier method of contraception during the first 7 days of taking the pills.
After an abortion in the first trimester of pregnancy, tablets can be started immediately. There is no need to use additional methods of contraception.
After childbirth or abortion in the second trimester of pregnancy it is recommended to take pills 21-28 days after childbirth or abortion in the second trimester, due to the increased risk of thromboembolic disorders in the postpartum period. If you start taking the pills later, then additional use of barrier methods of contraception should be recommended during the first 7 days of taking the pills. If sexual intercourse has already taken place, then the possibility of pregnancy should be excluded before taking the pills or wait for the onset of menstruation.
Missed pills
less than 12 hours, then the effectiveness of contraception is not reduced. The pill should be taken as soon as possible (as soon as the woman remembers about it) and continue taking the pills as usual. This does not apply to reddish-brown tablets, because. they do not contain hormones.
If the gap since the last pill is more than 12 hours the effectiveness of contraception is reduced. In this case, two main rules should be followed:
1. pills should not be missed for more than 7 days;
2. In order to effectively suppress the action of the hypothalamic-pituitary-ovarian axis, it is necessary to take the tablets for 7 days without interruption.
Thus, in daily practice, the following can be recommended:
1 Week: the woman should take the last missed tablet as soon as she remembers, even if she has to take 2 tablets at the same time. She should then continue taking the tablets as usual. For the next 7 days, you should also use a barrier method of contraception, such as a condom. If sexual intercourse has taken place within the previous 7 days, then pregnancy is possible. The more pills missed, and the closer the break in taking the pills, the higher the risk of pregnancy.
2 a week: the woman should take the last missed tablet as soon as she remembers, even if she has to take 2 tablets at the same time. She should then continue taking the tablets as usual. If she has taken her pills correctly during the previous 7 days, then there is no need to use additional contraceptives. However, if this is not the case, or more than 1 tablet was missed, then an additional method of contraception should be recommended for the next 7 days.
3 a week: the likelihood that contraception will be ineffective is very high due to the approaching break in taking the pills. However, you can take action by adjusting your pill intake. You can use one of the following alternative methods without the need to use additional methods of contraception, provided that during the previous 7 days the tablets were used in strict accordance with the scheme. Otherwise, the first of the following methods should be recommended and additional methods of contraception should be used for the next 7 days.
1. The woman should take the last missed tablet as soon as she remembers, even if she has to take 2 tablets at the same time. Then you should continue taking the tablets as usual. She should start taking the pills from the next pack immediately after taking the last pill from this pack, i.e. without taking a break between packs. Bleeding is unlikely until the end of the second pack, but spotting or light bleeding may occur on the days of taking the tablets.
2. It may also be recommended to stop taking the tablets from the current package. In this case, the woman should take a 7-day break from taking pills, including days of missing pills, and then proceed to the next pack.
If a woman misses her pills and there is no spotting during her first regular pill break, there is a possibility of pregnancy.
If vomiting appears within 3-4 hours after taking the tablet, then the absorption of the drug may not have been complete. In this case, you should use the above recommendations about skipping the pill. Diarrhea can reduce the effectiveness of contraception by preventing complete absorption. If a woman does not wish to change her usual tablet-taking pattern, she should take the additional tablet(s) needed from the next pack.
How to delay or change the day your period starts
To delay the onset of menstruation, a woman should start taking pills from the next pack of Rigevidon 21+7 after taking the last pill from the current pack, i.e. without taking a break. You can prolong taking the pills until this package runs out. During such an extension, bleeding or spotting may occur. Regular intake of Rigevidon 21+7 is resumed after the usual 7-day break in taking the tablets.
To move her period to a different day of the week than she is used to on her current pill schedule, she may be advised to shorten her upcoming pill break by as many days as she wants. The shorter the break, the more likely it is that she won't bleed and she may have spotting or spotting while taking the second pack of pills (which is also possible if her period is delayed). It is important to emphasize that you should not increase the break in taking the pills.
Relatively rare but serious side effects in which the drug should be discontinued
From the side of the cardiovascular system: arterial thromboembolic disorders (in particular, myocardial infarction, cerebrovascular disorders), venous thromboembolic disorders (phlebitis, pulmonary embolism), arterial hypertension, coronary artery disease.
From the side of metabolism: hyperlipidemia (hypertriglyceridemia and/or hypercholesterolemia).
From the endocrine system: diabetes mellitus, severe mastodynia, benign mastopathy, pituitary adenoma with prolactinoma (occasionally in combination with galactorrhea).
From the side of the central nervous system: severe headaches, migraine, nausea, visual disturbances, worsening of epilepsy.
nausea, liver adenoma, cholestatic jaundice.
Dermatological reactions: chloasma.
More frequent but less significant side effects that usually do not require discontinuation of the drug, but may consider switching to another contraceptive
From the side of the central nervous system: mild headaches, irritability.
From the reproductive system: soreness in the mammary glands, spotting, oligomenorrhea, amenorrhea, changes in libido.
Others: nausea, weight gain, heaviness in the legs, eye irritation when wearing contact lenses.
Other side effects
Dermatological reactions: rarely - acne, seborrhea, hypertrichosis.
From the digestive system: rarely - vomiting, cholelithiasis.
Others: rarely - depression, allergic reactions.
After discontinuation: post-therapeutic amenorrhea.
Amenorrhea associated with anovulation (more common in women with a history of irregular menstruation) may occur after discontinuation of the contraceptive and usually disappears spontaneously. With a longer duration of this condition, an examination should be carried out to ensure that there is no dysfunction of the pituitary gland before prescribing the drug for further use.
- venous thromboembolism or a history of venous thromboembolism (deep vein thrombosis, pulmonary embolism), both in the presence of risk factors and in their absence;
- arterial thromboembolism or a history of arterial thromboembolism, in particular myocardial infarction, cerebrovascular disorders;
- serious or multiple risk factors for the development of venous or arterial thrombosis;
- prodromal symptoms of thrombosis in history (for example, transient cerebral ischemia, angina pectoris);
- pregnancy or suspected pregnancy;
- heart disease, incl. pathology of heart valves, arrhythmia;
- severe arterial hypertension;
- diabetes mellitus complicated by micro- or macroangiopathy;
- visual impairment of vascular origin;
- malignant tumor of the breast;
- malignant endometrial tumors or other known or suspected estrogen-dependent neoplastic changes;
- serious or recent violations of liver function in the presence of abnormal laboratory parameters of liver function;
- benign or malignant tumors of the liver, incl. in history;
- vaginal bleeding of unknown etiology;
- migraine with focal neurotic symptoms;
- hypersensitivity to the components of the drug.
If the symptoms listed above appear for the first time during the use of the drug, then you should immediately stop taking it.
Use during pregnancy and lactation
Rigevidon 21+7 is contraindicated in pregnancy. If pregnancy occurs during the use of Rigevidon 21+7, you should immediately stop taking it.
Clinical data on a limited number of detected pregnancies do not illustrate the undesirable effect of levonorgestrel on the fetus.
The results of most epidemiological studies have found neither an increased risk of birth defects in children born to women who took oral contraceptives before pregnancy, nor the presence of a teratogenic or fetotoxic effect as a result of accidental exposure of the fetus to a combination of estrogens and progestogens.
The use of combined oral contraceptives can cause a decrease in production and a change in the composition of breast milk. Thus, as a rule, oral contraceptives should not be used until the end of the breastfeeding period. Small doses of hormones and/or their metabolites may be excreted in breast milk.
Prior to the appointment of oral contraceptives or the resumption of their use, a thorough history (including family history) should be taken, as well as a physical examination should be performed to identify contraindications and risk factors. This procedure should be carried out at least once a year during the entire period of use of oral contraceptives. It is also important to conduct periodic medical evaluation due to the possibility of contraindications (eg, transient cerebral ischemia) or risk factors (eg, hereditary venous or arterial thrombotic disorders) while taking oral contraceptives. The frequency and nature of such assessments depend on the condition of the woman, but blood pressure, the condition of the mammary glands, abdominal organs and small pelvis, incl. conduct a cytological examination of the cervix and appropriate laboratory tests.
Women should be reminded that oral contraceptives do not protect against HIV infection (AIDS) or other sexually transmitted infections. At risk of HIV infection/AIDS, the correct and consistent use of condoms should be recommended, incl. in combination with other methods of contraception.
When using oral contraceptives, smoking increases the risk of serious side effects from the cardiovascular system. The risk increases with age depending on the number of cigars smoked, especially in women over 35 who smoke. All women taking oral contraceptives should be strongly advised to refrain from smoking. For women over 35 who smoke, other methods of contraception should be considered.
If a woman is exposed to any of the risk factors listed below, the benefits of using combined oral contraceptives should be carefully weighed against the possible risk in each case and discussed with the woman before using combined oral contraceptives. If any of these symptoms or risk factors worsen, worsen, or appear, the woman should be advised to contact her doctor, who will decide whether or not to stop taking oral contraceptives.
Circulatory disorders
Epidemiological studies have shown an association between the use of oral contraceptives and an increased risk of arterial and venous thrombosis and thromboembolic disorders such as myocardial infarction, stroke, deep vein thrombosis and pulmonary embolic disorders.
The drug should be discontinued when symptoms appear that indicate the inevitable development of complications:
- severe abnormal headaches, visual disturbances, increased blood pressure, clinical signs of deep vein thrombosis or pulmonary embolic disorders.
Venous thromboembolism (VTE), which is manifested by deep vein thrombosis and / or pulmonary embolic disorders, can occur against the background of the use of any oral contraceptives. The occurrence of VTE in women using oral contraceptives with low estrogen content (less than 50 mcg of ethinylestradiol) is approximately 4 cases per 10,000 women per year, compared with 0.5 cases per 10,000 women who do not use oral contraceptives per year. However, the likelihood of VTE as a result of the use of oral contraceptives is much lower than as a result of pregnancy (6 cases per 10,000 women per year).
Thrombosis of other blood vessels has been reported very rarely, and hepatic, mesenteric, renal, or retinal veins and arteries may be affected in women taking oral contraceptives. There is no consensus as to whether these lesions are associated with the use of contraceptives.
The risk of developing thromboembolism (venous and / or arterial) increases:
- with age;
- when smoking (women over 35 are advised to stop smoking if they want to take oral contraceptives);
- with a hereditary predisposition, for example, the presence of venous or arterial thromboembolism in siblings or parents at a relatively young age (if a hereditary predisposition is suspected, a woman should be referred to a specialist before she decides to take oral contraceptives);
- with obesity (body mass index above 30 kg / m 2);
- with dyslipoproteinemia;
- with arterial hypertension;
- with diseases of the heart valves;
- with atrial fibrillation;
- with prolonged immobilization, major surgery, surgery on the legs or serious injury. In such cases, it is recommended to interrupt the use of oral contraceptives (in the case of a planned operation, at least 4 weeks before it) and not resume taking until 2 weeks have passed after the full restoration of an active lifestyle.
There is no consensus on the possible impact of varicose veins and superficial thrombophlebitis on venous thromboembolism.
The increased risk of thromboembolism during childbirth should be taken into account.
Other pathological conditions that may be associated with circulatory disorders include diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis), and sickle cell anemia.
If migraine attacks become more frequent or more severe (which may precede cerebrovascular disorders), the patient should immediately stop taking oral contraceptives.
Biochemical factors that characterize hereditary or acquired predisposition to venous or arterial thrombosis include resistance to activated protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C or S deficiency, the presence of antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).
Tumors
Some epidemiological studies have reported an increased risk of cervical cancer with long-term use of oral contraceptives, but there is no evidence to what extent this is influenced by sexual behavior and other factors, such as human papillomavirus (HPV).
A meta-analysis of 54 epidemiological studies showed that the relative risk (RR) of diagnosed breast cancer is only slightly higher (RR=1.24) in women taking combined oral contraceptives. This figure gradually decreases over the next 10 years after stopping oral contraceptives. Because breast cancer is relatively rare among women under 40 years of age, the increase in the number of diagnosed cases of breast cancer among women who currently or have used oral contraceptives is small compared to the lifetime risk of breast cancer.
These studies do not provide evidence for a causal relationship. The observed pattern of increased risk may be due to earlier diagnosis of breast cancer among women who take oral contraceptives, the biological effects of taking oral contraceptives, or a combination of both. Diagnosed cases of breast cancer among women taking oral contraceptives tend to be clinically less progressive compared to diagnosed cases of breast cancer among women who did not take oral contraceptives
There have been reports of the occurrence of benign and malignant liver tumors among women taking combined oral contraceptives. These tumors in some cases led to life-threatening intra-abdominal bleeding. As a differential diagnosis, the presence of a liver tumor should be considered when complaining of severe pain in the upper abdomen or signs of intra-abdominal bleeding in women taking oral contraceptives.
Other pathological conditions
Women with or a family history of hypertriglyceridemia may be at an increased risk of pancreatitis when taking oral contraceptives.
In acute or chronic liver dysfunction, the drug should be discontinued until the laboratory parameters of liver function return to normal. Steroid hormones may be poorly absorbed by patients with impaired liver function.
Women with hyperlipidemia when using oral contraceptives require careful monitoring.
Despite the fact that a slight increase in blood pressure has been reported in many women taking oral contraceptives, cases of clinically significant increase in blood pressure are rare. If persistent arterial hypertension develops as a result of the use of this drug, then the use should be stopped and treatment of arterial hypertension should be started. The use of oral contraception can be resumed, if necessary, as soon as normal blood pressure levels are achieved against the background of antihypertensive therapy.
The following conditions may appear or worsen, both during pregnancy and during the use of oral contraceptives, but there is no convincing evidence of a relationship with the use of oral contraceptives:
- jaundice and / or itching associated with bile stasis;
- the formation of stones in the gallbladder;
- porphyria;
- systemic lupus erythematosus;
- hemolytic-uremic syndrome;
- chorea;
- herpes of pregnant women;
- hearing loss due to otosclerosis.
Oral contraceptives may affect peripheral insulin resistance and glucose tolerance. Therefore, patients with diabetes require careful monitoring during the use of oral contraceptives.
Rigevidon 21+7 contains lactose and sucrose. Patients with rare hereditary conditions such as galactose intolerance, lactase deficiency, glucose-galactose malabsorption or fructose intolerance should not take this medicinal product.
An association has been reported between the development of Crohn's disease and ulcerative colitis and the use of combined oral contraceptives.
Occasionally, chloasma may develop, especially in women with a history of chloasma during pregnancy. Women who are predisposed to chloasma should avoid direct sunlight or ultraviolet radiation while taking oral contraceptives.
There are reports of cases of retinal thrombosis while taking oral contraceptives. Oral contraceptives should be discontinued with unexplained partial or complete loss of vision, the onset of proptosis or diplopia, with swelling of the optic nerve, pathological changes in the retinal vessels.
With the development of depression against the background of the use of oral contraceptives, they should be discontinued, in such cases it is recommended to use alternative methods of contraception until it is clarified whether the development of depression is associated with taking oral contraceptives. Women with a history of depression require careful clinical monitoring. If symptoms of depression recur, oral contraceptives should be discontinued.
Medicines containing St. John's wort (Hypericum perforatum) should not be used while taking Rigevidon 21+7 due to the possibility of reducing the concentration of active substances in plasma and reducing the clinical efficacy of Rigevidon 21+7.
The effectiveness of oral contraceptives may decrease as a result of missed pills or due to vomiting or due to the simultaneous use of another drug.
When taking any oral contraceptives, irregular bleeding (spotting or spotting) is possible, especially during the first months. Therefore, bleeding irregularity should be assessed after an adaptation period of approximately 3 cycles.
If bleeding remains irregular or becomes irregular after a previously stable cycle, the possibility of non-hormonal causes should be considered and an appropriate diagnosis should be made to rule out malignancy or pregnancy. If non-hormonal causes are excluded, then the use of high-hormonal oral contraceptives may need to be considered.
Sometimes bleeding may not occur during a break in taking the pills. When using the drug in accordance with the dosing regimen, the onset of pregnancy is unlikely. However, if the dosage regimen is violated, the possibility of pregnancy should be excluded before continuing the use of oral contraceptives.
Taking hormonal contraceptives may affect the results of laboratory parameters, incl. on biochemical indicators of the function of the liver, thyroid gland, functional tests of the adrenal glands and kidneys; the plasma concentration of transport proteins, eg corticosteroid-binding globulin and lipid/lipoprotein fractions; on parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis. As a rule, changes remain within the normal range.
Influence on the ability to drive vehicles and control mechanisms
Rigevidon 21 + 7 does not affect or practically does not affect the ability to drive vehicles or other mechanisms with an increased risk of injury.
Results of experimental studies
The acute toxicity of ethinylestradiol and levonorgestrel is low. Because of the variation noted, preclinical results are of limited predictive value in human estrogen use. In experimental animals, estrogens showed an embryo-lethal effect already at relatively small doses; malformations of the genitourinary tract and feminization of male embryos were observed. Levonorgestrel had a virilizing effect on female embions. Reproductive toxicology studies in rats, mice and rabbits showed no teratogenic effect, regardless of sexual differentiation.
Preclinical data based on conventional studies of repeated dose toxicity, genotoxicity and carcinogenic potential have not revealed any risks to humans, other than those described above in other sections of the instructions.
Symptoms: nausea, vomiting and minor vaginal bleeding in young girls are possible. There are no reports of serious adverse effects in case of an overdose of the drug.
Treatment: there is no antidote, the possibility of further use of the drug depends on the clinical symptoms of overdose.
Interaction with drugs that increase the excretion of sex hormones can lead to bleeding and reduce the effectiveness of contraception. Such an effect is possible when interacting with hydantoin derivatives (for example, with phenytoin, barbiturates, primidone, carbamazepine, rifampicin). Other drugs that appear to reduce the effectiveness of contraceptives include oxcarbazepine, topiramate, and griseofulvin. It is believed that the mechanism of this interaction is associated with the induction of liver enzymes by these drugs. The maximum induction of enzymes, as a rule, is observed no earlier than 2-3 weeks after the start of treatment, but after its completion it can persist for 4 weeks.
Contraceptive failure has also been observed with antibiotics such as ampicillin and tetracycline, although their mechanism of action is unclear.
With short-term use of drugs that cause the induction of liver enzymes, from the moment of initiation and within 4 weeks after discontinuation, the use of barrier methods of contraception is recommended. Women who are indicated for short-term antibiotics should use barrier contraceptive methods in parallel with oral contraceptives during antibiotics and for 7 days after stopping them. If during the application of such additional measures the tablets in the current package run out, then you should start taking the tablets from the next package without interruption. If the patient does not bleed after finishing taking the pills from the second pack, she should consult a doctor to rule out the possibility of pregnancy.
If the use of such drugs will be prolonged, then the use of other methods of contraception should be recommended.
It is not necessary to simultaneously prescribe drugs containing St. Bleeding and unplanned pregnancy have been reported. This is due to the fact that St. John's wort causes the induction of liver enzymes. This effect may continue for at least 2 weeks after discontinuation of the drug containing St. John's wort.
Co-administration of ritonavir can also cause induction of liver enzymes, which leads to a decrease in the effectiveness of contraception.
Rigevidon 21+7 may increase plasma concentrations of cyclosporine and diazepam (as well as other hydroxylated benzodiazepines), probably due to inhibition of their metabolism in the liver.
Rigevidon 21+7 is able to increase the bioavailability of imipramine, which increases the risk of intoxication.
Reddish-brown tablets are designed to ensure the continuity of the drug. They contain iron fumarate at a dose that is insufficient to treat iron deficiency anemia, but this dose of iron must be taken into account when prescribing other iron-containing drugs.
To determine the potential interaction, you should study the instructions for use of another drug.
