Rigavidon, 0.15 mg+0.03 mg 21 pcs

Pharmacodynamics

Rigevidone is an oral monophasic combined estrogen-gestagen contraceptive.
When taken orally, it inhibits pituitary gonadotropic hormone secretion.

The contraceptive effect is associated with several mechanisms. As a gestagenic component (progestin) contains a derivative of 19-nortestosterone – levonorgestrel, which is superior in activity to the corpus luteum hormone progesterone (and the synthetic analog of the latter – pregnin), acts at the level of receptors without prior metabolic transformations. The estrogenic component is ethinyl estradiol.

Under the influence of levonorgestrel there is a blockade of the release of releasing rhysing hormones (LH and FSH) of the hypothalamus, inhibition of secretion of gonadotropic hormones by the pituitary gland, which leads to inhibition of maturation and release of the egg ready for fertilization (ovulation). Contraceptive effect is enhanced by ethinyl estradiol. Maintains high viscosity of cervical mucus (makes it difficult for sperm to enter the uterine cavity). In addition to the contraceptive effect of regular use normalizes the menstrual cycle and contributes to the prevention of a number of gynecological diseases, including the tumor nature.

Pharmacokinetics

Levonorgestrel is quickly absorbed (less than 4 hours). Levonorgestrel has no effect of first passage through the liver. When levonorgestrel is coadministered with ethinylestradiol, there is a dose-response relationship with maximum plasma concentration. TCmax (time of reaching maximum concentration) of levonorgestrel is 2 hours, T1/2 (elimination half-life) is 8-30 hours (average 16 hours). (on average 16 hours). Most of the levonorgestrel is bound in the blood with albumin and hGH (sex hormone-binding globulin).

Ethinylestradiol is quickly and almost completely absorbed from the intestine. Ethinylestradiol has an inherent effect of primary passage through the liver, TCmax is 1.5 hours, and the elimination half-life is about 26 hours.

When administered orally, ethinylestradiol is excreted from the blood plasma within 12 hours, the half-life is 5.8 hours.
Metabolism of ethinylestradiol is performed in the liver and intestine. Metabolites of ethinylestradiol are water-soluble products of sulfate or glucuronide conjugation, enter the intestine with bile, where they undergo disintegration by intestinal bacteria.
Both components (levonorgestrel and ethinylestradiol) are excreted with breast milk. The active substances are metabolized in the liver, the T1/2 is 2-7 h.

Levonorgestrel is excreted by the kidneys (60%) and through the intestine (40%); ethinylestradiol by the kidneys (40%) and through the intestine (60%).

Indications

Oral contraception, functional disorders of the menstrual cycle (including dysmenorrhea without an organic cause, dysfunctional metrorrhagia, premenstrual syndrome).

Pharmacological effect

Pharmacodynamics

Rigevidon is an oral monophasic combined estrogen-progestogen contraceptive drug.
When taken orally, it inhibits the pituitary secretion of gonadotropic hormones.

The contraceptive effect is associated with several mechanisms. As a gestagenic component (progestin), it contains a derivative of 19-nortestosterone – levonorgestrel, which is more active than the corpus luteum hormone progesterone (and a synthetic analogue of the latter – pregnin), acts at the receptor level without preliminary metabolic transformations. The estrogenic component is ethinyl estradiol.

Under the influence of levonorgestrel, there is a blockade of the release of releasing hormones (LH and FSH) of the hypothalamus, inhibition of the pituitary gland’s secretion of gonadotropic hormones, which leads to inhibition of the maturation and release of an egg ready for fertilization (ovulation). The contraceptive effect is enhanced by ethinyl estradiol. Maintains high viscosity of cervical mucus (makes it difficult for sperm to enter the uterine cavity). Along with the contraceptive effect, when taken regularly, it normalizes the menstrual cycle and helps prevent the development of a number of gynecological diseases, incl. tumor nature.

Pharmacokinetics

Levonorgestrel is rapidly absorbed (less than 4 hours). Levonorgestrel does not have a first-pass effect through the liver. When levonorgestrel is co-administered with ethinyl estradiol, there is a relationship between the dose and maximum plasma concentration. TCmax (time to reach maximum concentration) of levonorgestrel is 2 hours, T1/2 (half-life) is 8-30 hours. (on average 16 hours). Most of levonorgestrel binds in the blood to albumin and SHBG (sex hormone binding globulin).

Ethinyl estradiol is rapidly and almost completely absorbed from the intestine. Ethinyl estradiol has a first pass effect through the liver, TCmax is 1.5 hours, half-life is about 26 hours.

When taken orally, ethinyl estradiol is released from the blood plasma within 12 hours, the half-life is 5.8 hours.
Ethinyl estradiol is metabolized in the liver and intestines. Ethinyl estradiol metabolites are water-soluble products of sulfate or glucuronide conjugation and enter the intestine with bile, where they undergo disintegration with the help of intestinal bacteria.
Both components (levonorgestrel and ethinyl estradiol) are excreted in breast milk. Active substances are metabolized in the liver, T1/2 is 2-7 hours.

Levonorgestrel is excreted by the kidneys (60%) and through the intestines (40%); ethinyl estradiol – by the kidneys (40%) and through the intestines (60%).

Special instructions

Before starting the use of hormonal contraception and subsequently every 6 months, a general medical and gynecological examination is recommended, including a cytological analysis of a smear from the cervix, assessment of the condition of the mammary glands, determination of blood glucose, cholesterol and other indicators of liver function, blood pressure monitoring, and urinalysis).

Prescribing Rigevidon to women with thromboembolic diseases at a young age and a family history of increased blood clotting is not recommended.

The use of oral contraception is allowed no earlier than 6 months after viral hepatitis, provided that liver functions are normalized.

If sharp pain appears in the upper abdomen, hepatomegaly and signs of intra-abdominal bleeding, a suspicion of a liver tumor may arise. If necessary, the drug should be discontinued.

If liver function is impaired while taking Rigevidon, consultation with a physician is necessary.

If acyclic (intermenstrual) bleeding occurs, Rigevidon should be continued, because in most cases, these bleedings stop spontaneously. If acyclic (intermenstrual) bleeding does not disappear or recurs, a medical examination should be performed to exclude organic pathology of the reproductive system.

In case of vomiting or diarrhea, the drug should be continued using another, non-hormonal method of contraception.

Women who smoke and take hormonal contraceptives have an increased risk of developing cardiovascular diseases with serious consequences (myocardial infarction, stroke). The risk increases with age and depending on the number of cigarettes smoked (especially in women over 35 years of age).

The drug should be stopped in the following cases:

– When migraine-like headache appears for the first time or worsens.
– The appearance of an unusually severe headache.
– When early signs of phlebitis or phlebothrombosis appear (unusual pain or swelling of the veins in the legs).
– If jaundice or hepatitis occurs without jaundice.
– For cerebrovascular disorders.
– When stabbing pain of unknown etiology appears when breathing or coughing, pain and a feeling of tightness in the chest.
– In case of acute deterioration of visual acuity.
– If thrombosis or heart attack is suspected.
– With a sharp increase in blood pressure.
– If generalized itching occurs.
– With increased frequency of epileptic seizures.
– 3 months before the planned pregnancy.
– Approximately 6 weeks before the planned surgical intervention.
– With prolonged immobilization.
– During pregnancy.

– Use for liver dysfunction: Contraindicated for use in severe liver diseases (including congenital hyperbilirubinemia – Gilbert, Dubin-Johnson and Rotor syndromes; liver tumors).

– Use for impaired renal function: Caution is required if it is necessary to prescribe the drug to patients with impaired renal function.

– Effect on the ability to drive vehicles and operate machinery: Taking the drug does not affect the ability to drive vehicles and operate other mechanisms, work with which is associated with an increased risk of injury.

Active ingredient

Levonorgestrel, Ethinyl estradiol

Composition

Active substances:

ethinyl estradiol: 0.03 mg,

levonorgestrel; 0.15 mg

Excipients:

in the tablet core:

colloidal silicon dioxide,

magnesium stearate,

talc,

corn starch,

lactose monohydrate;

in tablet shell:

sucrose,

talc,

calcium carbonate,

titanium dioxide,

copovidon,

macrogol 6000,

colloidal silicon dioxide,

povidone,

carmellose sodium.

Pregnancy

The drug is contraindicated during pregnancy and lactation (breastfeeding).

Contraindications

– Severe liver diseases (including congenital hyperbilirubinemia – Gilbert, Dubin-Johnson and Rotor syndromes).
– Cholecystitis.
– Presence or history of severe cardiovascular and cerebrovascular diseases.
– Thromboembolism and predisposition to them.
– Malignant tumors (primarily breast or endometrial cancer).
– Liver tumors.
– Familial forms of hyperlipidemia.
– Severe forms of arterial hypertension.
– Endocrine diseases (including severe forms of diabetes).
– Sickle cell anemia.
– Chronic hemolytic anemia.
– Vaginal bleeding of unknown etiology.
– Bubble drift.
– Migraine.
– Otosclerosis.
– History of idiopathic jaundice in pregnancy.
– Severe skin itching during pregnancy.
– Herpes in pregnant women.
– Age over 40 years.
– Pregnancy.
– Lactation period (breastfeeding).
– Hypersensitivity to the components of the drug.

The drug should be used with caution when:

– Diseases of the liver and gall bladder.
– Epilepsy.
– Depression.
– Ulcerative colitis.
– Uterine fibroids.
– Mastopathy.
– Tuberculosis.
– Kidney diseases.
– For diabetes mellitus.
– Diseases of the cardiovascular system.
– Arterial hypertension.
– Impaired kidney function.
– Varicose veins.
– Phlebitis.
– Multiple sclerosis.
– Lesser chorea.
– In adolescence (without regular ovulatory cycles).

Side Effects

The drug is usually well tolerated.

Possible side effects of a transient nature, spontaneously passing: nausea, vomiting, headache, engorgement of the mammary glands, changes in body weight and libido, changes in mood, acyclic bleeding, in some cases – swelling of the eyelids, conjunctivitis, blurred vision, discomfort when wearing contact lenses (these phenomena are temporary and disappear after discontinuation without prescribing any therapy).

With long-term use, chloasma, hearing loss, generalized itching, jaundice, calf muscle cramps, and an increase in the frequency of epileptic seizures can very rarely occur.

Hypertriglyceridemia, hyperglycemia, decreased glucose tolerance, increased blood pressure (BP), thrombosis and venous thromboembolism, jaundice, skin rashes, changes in the nature of vaginal secretion, vaginal candidiasis, increased fatigue, diarrhea are rarely observed.

Interaction

Barbiturates, some antiepileptic drugs (carbamazepine, phenytoin), sulfonamides, pyrazolone derivatives can enhance the metabolism of the steroid hormones included in the drug.

A decrease in contraceptive effectiveness can also be observed when administered simultaneously with certain antimicrobial agents (including ampicillin, rifampicin, chloramphenicol, neomycin, polymyxin B, sulfonamides, tetracyclines), which is associated with changes in intestinal microflora.

When used simultaneously with anticoagulants, coumarin or indanedione derivatives, additional determination of the prothrombin index and a change in the dose of the anticoagulant may be required.

When using tricyclic antidepressants, maprotiline, beta-blockers, their bioavailability and toxicity may increase.

When using oral hypoglycemic drugs and insulin, it may be necessary to change their dose.

When combined with bromocriptine, its effectiveness decreases.

When combined with drugs with potential hepatotoxic effects, for example, with the drug dantrolene, increased hepatotoxicity is observed, especially in women over 35 years of age.

Rigevidon should be used with caution in combination with the drugs listed above.

Overdose

Cases of toxic effects due to overdose are unknown.

Storage conditions

The drug should be stored at a temperature of 15° to 30°C.

Shelf life

5 years.

Manufacturer

Gedeon Richter, Hungary