Nemestran^® (Capsules) Instructions for Use

Marketing Authorization Holder

Aventis Pharma Limited (United Kingdom)

Manufactured By

Patheon UK, Limited (United Kingdom)

ATC Code

G03XA02 (Gestrinone)

Active Substance

Gestrinone

Dosage Form

Nemestran®

Capsules 2.5 mg: 8 pcs.

Dosage Form, Packaging, and Composition

Capsules are hard gelatin, size No. 4, opaque, with a white body and cap, both halves of the capsule bear the Roussel company logo; the capsule contents are a yellowish powder.

Excipients: corn starch, lactose, microcrystalline cellulose, colloidal silicon dioxide, magnesium stearate, talc.

Capsule shell composition: titanium dioxide, gelatin.

8 pcs. – blisters (1) complete with a “calendar disk” – cardboard packs.

Clinical-Pharmacological Group

Gestagen

Pharmacotherapeutic Group

Progestogen

Pharmacological Action

A synthetic steroid hormone, a derivative of 19-nortestosterone. Depending on the test model, it exhibits both antiprogestin and progestin activity. It has antigonadotropic, antiestrogenic, and weak androgenic effects.

Gestrinone has an inhibitory effect on endometrial tissue. Its action is believed to be associated with direct suppression of the synthesis-release mechanism of pituitary gonadotropins and with a direct antagonistic effect on endometrial tissue.

Pharmacokinetics

After administration of 2.5 mg of gestrinone, the maximum concentration of the drug in the blood is 19 mol/ml and is reached on average after 2 hours.

The T_1/2 of the drug from plasma is approximately 27 hours.

The V_d is 67 L (with intravenous administration in men).

Metabolism occurs in the liver via hydroxylation, leading to the formation of 3 main conjugated metabolites. It is excreted 40-45% by the kidneys (1% as free steroid) and 30-35% in feces.

Indications

• Endometriosis.

ICD codes

Dosage Regimen

The first dose (2.5 mg) is taken on the first day of the menstrual cycle after receiving negative pregnancy test results. The second dose should be taken on the fourth day. The usual regimen is 2 times a week, strictly on the same days. The number of capsules can be increased to three per week, especially in case of uterine bleeding in the intermenstrual period.

The duration of treatment is 6 months without interruption.

If one dose is missed, the capsule should be taken the next day, subsequently maintaining the usual weekly regimen. If two or more doses of Nemestran^® are missed, treatment should be discontinued and resumed on the first day of the next menstrual cycle according to the usual regimen.

Adverse Reactions

Uterine bleeding at the beginning of therapy, especially if the first dose was not taken on the first day of the menstrual cycle.

Acne, seborrhea, fluid retention, hirsutism, hair loss, voice change, reduction in breast size.

Change in libido, weight gain, hot flashes, headache, increased nervous excitability, depression, dyspeptic phenomena, skin hyperpigmentation, increased activity of liver transaminases, arthralgia, convulsions. Rarely – benign intracranial hypertension.

Contraindications

• Pregnancy;
• Lactation period;
• Acute heart failure;
• Renal or hepatic failure;
• Metabolic disorders and/or history of thrombophlebitis when treated with drugs containing estrogens and/or progestogens;
• Hypersensitivity to any component of the Nemestran^® drug;

Use with caution in migraine.

Use in Pregnancy and Lactation

Nemestran^® is absolutely contraindicated during pregnancy and breastfeeding. If pregnancy is detected, the drug should be discontinued, as animal experiments have shown that the drug has embryotoxic effects, albeit at doses significantly higher than those used in clinical practice.

Use in Hepatic Impairment

Contraindication: hepatic failure.

Use in Renal Impairment

Contraindication: renal failure.

Special Precautions

Nemestran^® at the recommended dose may suppress ovulation, but the possibility of pregnancy during treatment remains. This means that Nemestran^® cannot be considered a contraceptive. Since the simultaneous administration of hormonal contraceptives may affect the activity of Nemestran^®, barrier methods of contraception should be used throughout the entire treatment period. Treatment must begin strictly on the first day of the menstrual cycle.

To ensure maximum effectiveness, it is necessary to strictly adhere to the treatment regimen.

Due to possible fluid retention during treatment with Nemestran^®, patients with heart and renal failure require special monitoring. It is recommended to regularly monitor AST, ALT, and lipid levels in patients with hyperlipidemia, as well as blood sugar levels in patients with diabetes mellitus.

Overdose

No information available. In case of ingestion of a large amount of the drug, gastric lavage should be performed.

Drug Interactions

Concomitant administration of antiepileptic drugs or rifampicin may lead to accelerated metabolism of gestrinone.

Storage Conditions

Store in a place protected from light and out of the reach of children at a temperature not exceeding 25°C (77°F). List B.

Shelf Life

Shelf life – 3 years. Do not use the drug after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

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.