Clostilbegyt^® (Tablets) Instructions for Use

Marketing Authorization Holder

Egis Pharmaceuticals PLC (Hungary)

ATC Code

G03GB02 (Clomifene)

Active Substance

Clomifene (Rec.INN registered by WHO)

Dosage Form

Clostilbegyt®

Tablets 50 mg: 10 pcs.

Dosage Form, Packaging, and Composition

Tablets white, yellowish-white, or grayish-white in color, round, flat, with a bevel, engraved with “CLO” on one side; odorless or almost odorless.

Excipients: lactose monohydrate – 100 mg, potato starch – 39 mg, talc – 5 mg, gelatin – 2 mg, magnesium stearate – 2 mg, stearic acid – 2 mg.

10 pcs. – blisters made of PVC/PVDX/aluminum foil (1) – cardboard packs.
10 pcs. – brown glass bottles with a PE cap, with first-opening control and a bellows cushion (1) – cardboard packs.

Clinical-Pharmacological Group

Gonadotropin production stimulant

Pharmacotherapeutic Group

Sex hormones and modulators of the genital system, synthetic ovulation stimulants

Pharmacological Action

Stimulator of gonadotropin production. An agent with antiestrogenic and estrogenic activity. It has a non-steroidal structure that is close to chlorotrianisene.

It is believed that the action of clomifene is due to specific binding to estrogen receptors in the hypothalamus and pituitary gland, which increases the secretion of pituitary gonadotropic hormones.

This in turn stimulates the maturation and endocrine activity of the follicle in the ovary, as well as the subsequent formation and stimulation of the corpus luteum function.

In high doses, it inhibits the secretion of gonadotropins. It does not possess progestogenic or androgenic activity.

Pharmacokinetics

When taken orally, it is well absorbed from the gastrointestinal tract. It is metabolized in the liver. Undergoes enterohepatic recirculation.

The T_1/2 is 5-7 days. It is excreted mainly with bile.

Indications

Anovulatory infertility (induction of ovulation); amenorrhea (dysgonadotropic form), secondary amenorrhea, post-contraceptive amenorrhea; Stein-Leventhal syndrome (polycystic ovary syndrome); oligomenorrhea; galactorrhea (against the background of a pituitary tumor); Chiari-Frommel syndrome (syndrome of prolonged postpartum amenorrhea-galactorrhea); androgen deficiency; in men – oligospermia.

ICD codes

Dosage Regimen

Take orally as a single daily dose.

Initiate therapy at a dose of 50 mg (one tablet) daily for five days.

Start treatment on or about the fifth day of the menstrual cycle.

If ovulation is confirmed but pregnancy does not occur, repeat the same regimen for at least three cycles.

If ovulation does not occur, increase the dose to 100 mg daily for five days in the next cycle.

Do not exceed a maximum single daily dose of 100 mg.

Do not exceed a maximum total course dose of 750 mg per cycle.

Discontinue treatment if ovarian hyperstimulation occurs.

For male infertility (oligospermia), use a dose of 50 mg once daily.

Undergo a thorough gynecological examination before each treatment cycle.

Monitor for ovarian enlargement and cystic transformation throughout therapy.

Adverse Reactions

From the digestive system nausea, vomiting; rarely – gastralgia, flatulence, diarrhea, acute abdomen syndrome.

From the nervous system headache, dizziness, drowsiness; rarely – slowing of mental and motor reactions, increased excitability, depression, insomnia.

From the organ of vision impaired light perception, double vision, blurred outlines, photophobia.

From the urinary system frequent urination; rarely – polyuria.

From the reproductive system and mammary glands breast induration, lower abdominal pain, dysmenorrhea, pathological uterine bleeding, ovarian enlargement (including cystic); rarely – vaginal dryness, menorrhagia.

Allergic reactions rarely – rash, urticaria, allergic dermatitis, vasomotor disorders.

Other rarely – increased appetite, increase or decrease in body weight, alopecia, soreness in the breast area, hot flashes.

Contraindications

Hypersensitivity to clomifene; hepatic and/or renal failure; pregnancy, lactation (breastfeeding); ovarian cysts (except for polycystic ovary syndrome); pituitary tumor or hypofunction; thyroid or adrenal dysfunction; metrorrhagia of unclear etiology; long-standing or recently developed visual disturbances; neoplasms of the genital organs; endometriosis; ovarian insufficiency against the background of hyperprolactinemia.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

Contraindicated for use in hepatic failure.

Use in Renal Impairment

Contraindicated for use in renal failure.

Special Precautions

It is recommended to check liver function before starting the use of clomifene.

Before using clomifene, a thorough gynecological examination must be performed. The use of clomifene is indicated in cases where the total level of gonadotropin in the urine is below the lower limit of normal or at the normal level, palpation of the ovaries reveals no abnormalities, and the functions of the thyroid gland and adrenal glands are normal.

In the absence of egg maturation, all other possible causes of infertility should be excluded or treated before using clomifene. If ovarian enlargement or cystic transformation is detected, the use of clomifene is not allowed until the ovaries return to normal size. Subsequently, the dose or duration of treatment should be reduced.

During treatment, constant supervision by a gynecologist is necessary, ovarian function should be monitored, vaginal examinations should be performed, and the “pupil” phenomenon should be observed. Often during the course of treatment, it is difficult to determine the moment of ovulation, and corpus luteum insufficiency is often observed. Therefore, after conception, it is recommended to start prophylactic administration of progesterone.

When treated with clomifene, the likelihood of multiple pregnancies, ectopic pregnancy, endometriosis, and growth of an existing uterine fibroid increases.

Hot flashes observed during the course of treatment stop after the end of clomifene intake. Cystic enlargement of the ovaries may also be observed, especially in Stein-Leventhal syndrome. In these cases, the size of the ovaries can reach 4-8 cm. In this case, body temperature should be monitored and treatment should be stopped as soon as it becomes biphasic.

Effect on the ability to drive vehicles and mechanisms

During the treatment period, caution must be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Compatible with gonadotropic hormone preparations.

Storage Conditions

Store at 15°C (59°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.