Regulon, 63 pcs.

Regulon is a monophasic hormonal contraceptive for oral administration containing a combination of estrogen (ethinyl estradiol) and gestagen (desogestrel).

It inhibits pituitary secretion of gonadotropic hormones. The contraceptive effect is due to the influence on the hypothalamic-pituitary-ovarian system.

Desogestrel is a synthetic gestagen, when taken orally inhibits the synthesis of LH and FSH in the pituitary gland and, by preventing follicle maturation, effectively blocks ovulation. It has anti-estrogenic, weak androgenic (anabolic) action, has no estrogenic effect.

Ethinyl estradiol is a synthetic analogue of the follicular hormone estradiol, is involved together with the corpus luteum hormone in the formation of the menstrual cycle. It prevents the maturation of an egg capable of fertilization.

The contraceptive effect is due, on the one hand, to a decrease in the susceptibility of the endometrium to the blastocyte and, on the other hand, to an increase in the viscosity of mucus in the cervix, which prevents the passage of sperm.

The drug has a favorable effect on lipid metabolism: it increases plasma HDL content without affecting LDL content.

When taking the drug, menstrual blood loss decreases significantly. Regular taking of the drug normalizes the menstrual cycle and helps to prevent development of some gynecologic diseases, including cancer.

It has a beneficial effect on the skin and significantly improves skin conditions in acne vulgaris.

Pharmacokinetics

Desogestrel

Absorption

Introduction. Desogestrel is rapidly and almost completely absorbed from the GI tract and is immediately metabolized to 3-keto-desogestrel, which is the biologically active metabolite of desogestrel.

Cmax is reached after 1.5 h and is 2 ng/ml. Bioavailability is 62-81%.

Distribution

3-keto-desogestrel binds to plasma proteins, mainly to albumin and to sex hormone-binding globulin (hSPG). Vd is 1.5 L/kg. Css is established by the second half of the menstrual cycle. 3-keto-desogestrel levels increase by a factor of 2 to 3.

Metabolism

In addition to 3-keto-desogestrel (which is formed in the liver and intestinal wall), other metabolites are formed: 3α-ON-desogestrel, 3β-ON-desogestrel, 3α-ON-5α-H-desogestrel (first phase metabolites). These metabolites have no pharmacological activity and partially, by conjugation (the second phase of metabolism), are converted to polar metabolites – sulfates and glucuronates. Clearance from blood plasma is about 2 ml/min/kg body weight.

The T1/2 of 3-keto-desogestrel is 30 hours. The metabolites are excreted in the urine and feces (4:6 ratio).

Ethinylestradiol

Ethinylestradiol is rapidly and completely absorbed from the gastrointestinal tract. Cmax is reached 1-2 hours after taking the drug and is 80 pg/ml. The bioavailability of the drug due to presystemic conjugation and “first pass” effect through the liver is about 60%.

Distribution

Ethinylestradiol is completely bound to plasma proteins, mainly to albumin. Vd is 5 l/kg. Css is established by 3-4 days of administration, with serum ethinylestradiol levels 30-40% higher than after a single dose of the drug.

Metabolism

The presystemic conjugation of ethinylestradiol is significant. Passing the intestinal wall (first phase of metabolism), it undergoes conjugation in the liver (second phase of metabolism). Ethinylestradiol and its conjugates of the first phase of metabolism (sulfates and glucuronides) are excreted in bile and enter enter enterohepatic circulation. Clearance from blood plasma is about 5 ml/min/kg body weight.

The T1/2 of ethinylestradiol averages about 24 hours. About 40% is excreted with the urine and about 60% with the feces.

Indications

Oral contraception.

Composition

1 tablet contains:

active ingredients:

ethinylestradiol 0.03 mg,

desogestrel 0.15 mg,

auxiliary substances:

α-tocopherol, 0.08 mg;

magnesium stearate, 0.08 mg;

Colloidal silicon dioxide – 0.8 mg;

Stearic acid – 0.8 mg;

povidone – 2.4 mg;

potato starch – 8 mg;

Lactose monohydrate – 67.66 mg,

film jacket:

propylene glycol – 0.03 mg;

macrogol 6000 – 0.22 mg;

hypromellose – 0.75 mg

How to take, the dosage

The drug is prescribed 1 tablet/day (if possible at the same time), starting on day 1 of the menstrual cycle for 21 days. This is followed by a 7-day break, during which menstrual bleeding occurs. Then you resume taking the pills from the next package (even if bleeding has not yet stopped). If you follow the rules of taking it, the contraceptive effect lasts even during the 7-day break.

If the first pill is taken on the 1st day of the menstrual cycle, no additional contraceptive methods are needed. You can also start taking the pills on days 2-5 of your menstrual cycle, but in this case you must use additional contraception in the first cycle for the first 7 days of taking the pills.

If more than 5 days have passed since the beginning of your period, you should postpone taking the drug until your next period.

Postpartum After delivery, non-breastfeeding women can be prescribed the drug after 21 days. No other contraceptive methods are necessary in this case. If the drug is prescribed later than 21 days after childbirth, then additional contraceptive methods should be used during the first 7 days of use. If sexual intercourse in the postpartum period was preceded by oral contraception, then it is necessary to wait with taking the pills until the first menstruation. In women who continue to breastfeed, combined oral contraceptives are not recommended because taking the drug may reduce milk production.

– After an abortion After an abortion, it is recommended that the drug be started immediately after surgery, in which case no additional contraceptive methods are necessary.

– When switching to Regulon When switching to Regulon after taking another estrogen-gestogen hormonal contraceptive, the first Regulon tablet should be taken the day after completion of the previous drug. No additional contraceptive methods are needed. If you switch to Regulon after taking another hormonal contraceptive containing only gestagen, the first tablet of Regulon should be taken on the first day of menstrual cycle; no additional contraceptive methods are needed. If no menstruation occurs while taking the previous drug, Regulon can be started on any day of the cycle, but in this case, additional contraceptive methods must be used during the first 7 days of taking it. The use of cervical cap with spermicidal gel, condom or abstinence from sexual intercourse is recommended as additional methods of contraception. The use of the calendar method as an additional method of contraception is not recommended.

If menstrual delay is necessary, the pills should be continued without a 7-day break. In this case, intermenstrual bleeding may occur, but this does not reduce the contraceptive effect of the drug. Regular taking Regulon can be restored after the usual 7-day break.

– If you miss a dose If you miss a dose, if you are no more than 12 hours late in taking the pill, you should take the missed pill and continue taking it at the usual time. If the delay in taking the pill was more than 12 hours, it is considered skipping the pill. The reliability of contraception in this cycle is not guaranteed, and the use of additional contraceptive methods is recommended. If you miss 1 tablet in the first or second week of the cycle, you should take 2 tablets the next day and then continue regular use, using additional contraception until the end of the cycle. If you miss 1 tablet in the third week of the cycle, in addition to the above measures, a 7-day break is excluded. If vomiting or diarrhea appears after taking the drug, absorption of the drug may be incomplete. If the symptoms stop within 12 hours, you should take 1 more tablet additionally. After this you should continue taking the tablets in the usual manner. If symptoms persist for more than 12 hours, additional contraceptive methods should be used for the next 7 days.

Interaction

When Regulon is used simultaneously with antispasmodics, phenobarbital derivatives, antibiotics (tetracycline, ampicillin, rifampicin, isoniazid, neomycin, penicillin, chloramphenicol), carbamazepine, phenylbutazone, analgesics, anxiolytics, activated carbon, sulfonamides, nitrofurans, migraine medications, griseofulvin, laxatives and some herbs (e.g. St. John’s wort) may change menstruation pattern and reduce the contraceptive effect of Regulon.

Regulon decreases the effectiveness of oral anticoagulants, anxiolytics (diazepam), tricyclic antidepressants, guanethidine, theophylline, caffeine, vitamins, clofibrate, GCS, paracetamol when used concomitantly.

The concomitant use of Regulon with oral hypoglycemic agents or insulin may impair carbohydrate metabolism control because Regulon may decrease carbohydrate tolerance and increase the need for insulin or oral hypoglycemic agents, which may require dose adjustments.

Special Instructions

Before starting to use the drug, a general medical (detailed family and personal history, blood pressure measurement, laboratory tests) and gynecological examination (including examination of the breasts, pelvic organs, cytological analysis of cervical smears) should be performed. Such examinations are performed regularly every 6 months while taking the drug.

The efficacy of Regulon decreases if the pills are missed or if there is vomiting or diarrhea or if other drugs are taken at the same time.

The effectiveness of Regulon may decrease if intermenstrual bleeding occurs after several months of use. If menstrual bleeding does not occur during a break, the pills can only be continued after pregnancy has been ruled out.

The risk of arterial or venous thromboembolic diseases increases with age, with smoking, with a family history of thromboembolic diseases, with obesity (body mass index over 30 kg/m 2), with dislipoproteinemia, In arterial hypertension, heart valve disease, atrial fibrillation, diabetes, prolonged immobilization (after major surgery, after surgery on the lower extremities, after severe trauma).

In the presence of congenital or acquired biochemical defects (resistance to activated protein C, hyperchromocysteinemia, protein C, S deficiency, antithrombin III deficiency, the presence of antiphospholipid antibodies) the risk of thromboembolic diseases also increases. Targeted treatment of the above conditions reduces the risk of thrombosis.

Pregnancy poses a greater risk of thrombosis than taking hormonal contraceptives.

The use of Regulon should be stopped immediately in the following cases:

– Occurrence of a severe headache for the first time or worsening of common migraines.
– Acute deterioration of visual acuity.
– Suspicion of myocardial infarction or thrombosis.
– Sudden increase in BP.
– Occurrence of jaundice or hepatitis without jaundice, intense generalized itching.
– Occurrence of epilepsy or increased frequency of epileptic seizures.
– In 4 weeks before the planned surgical intervention and in case of prolonged immobilization (Regulon administration can be resumed after 2 weeks after immobilization).
– Development of pregnancy.

– Application in liver function disorders: Contraindicated in hepatic insufficiency.

– Use in renal dysfunction: With caution and only after careful assessment of benefits and risks of use the drug should be administered in renal failure (including history).

Influence on driving and operating machinery: Studies of the effect of Regulon on the ability to drive and operate machinery have not been conducted.

Contraindications

Side effects

Side effects requiring drug withdrawal

Cardiovascular system: arterial hypertension; rarely – arterial and venous thromboembolism (including Myocardial infarction, stroke, deep vein thrombosis of the lower extremities, pulmonary embolism); very rare – arterial or venous thromboembolism of hepatic, mesenteric, renal, retinal arteries and veins.

Sensory organs: hearing loss associated with otosclerosis.

Others: hemolytic-uremic syndrome, porphyria; rarely – exacerbation of reactive systemic lupus erythematosus; very rare – Sydenham’s chorea (which resolves after discontinuation of the drug).

Other side effects that occur more frequently, but are less severe. The appropriateness of continuing the drug is decided individually after consultation with a physician, based on the benefit/risk ratio.

In the genital system: acyclic bleeding/bloody vaginal discharge, amenorrhea after drug withdrawal, changes in vaginal mucus, development of vaginal inflammation, candidiasis, tension, pain, breast enlargement, galactorrhea.

In the digestive system: nausea, vomiting, Crohn’s disease, ulcerative colitis, occurrence or exacerbation of jaundice and/or pruritus associated with cholestasis, cholithiasis.

Dermatological reactions: erythema nodosum, erythema exudative, rash, chloasma.

CNS disorders: headache, migraine, mood swings, depression.

A visual organ: increased sensitivity of the cornea (when wearing contact lenses).

Metabolic disorders: fluid retention in the body, change (increase) in body weight, decreased carbohydrate tolerance.

Others: allergic reactions.

Overdose

Symptoms: metrorrhagia. Administration of the drug in high doses was not accompanied by the occurrence of severe symptoms.

Treatment: gastric lavage is recommended during the first 2-3 hours after high-dose drug administration. There is no specific antidote, treatment is symptomatic.

Pregnancy use

Regulon is contraindicated in pregnancy. Regulon should be discontinued 3 months before the planned pregnancy. If pregnancy occurs, the drug should be stopped.

Epidemiological studies have proven that there is no increase in the incidence of malformations among children born to women who have taken hormonal contraceptives before pregnancy.

There were no teratogenic effects detected when the drug was taken in early pregnancy.

The use of Regulon is contraindicated during lactation (breastfeeding) because it reduces the secretion of breast milk and changes its composition. In addition, the active substances are excreted in small quantities with breast milk.