Oxyprogesterone capronate

I N S T R U C T I O N for medical use of the medicinal product OXYPROGESTERONE CAPRONATE (OXYPROGESTERONE CAPRONATE)

Composition:

active substance: 1 ml of solution contains hydroxyprogesterone caproate (calculated as dry substance) 125 mg;

excipients: benzyl benzoate, refined olive oil.

Pharmaceutical form. Oil solution for injection.

Main physicochemical properties: clear oily liquid of light yellow to greenish-yellow color.

Pharmacotherapeutic group. Sex hormones and drugs used in disorders of the genital system. Progestogens. ATC code G03D A03.

Pharmacological properties.

Pharmacodynamics.

Hydroxyprogesterone caproate is a synthetic analogue of the hormone of the corpus luteum (progesterone). Its biological properties are similar to those of progesterone: it induces transformation of the endometrium from the proliferative phase, caused by follicular hormone, into the secretory phase, and after fertilization promotes its transition into a state necessary for the development of the fertilized ovum; reduces excitability and contractility of the uterine and fallopian tube musculature, and stimulates development of the terminal elements of the mammary gland. Compared to progesterone, it is more stable in the body, acts more slowly, and has a longer duration of effect. After a single intramuscular injection, its action persists for 7 to 14 days.

Pharmacokinetics.

After intramuscular injection, it is slowly absorbed from the injection site. Therapeutic concentration is maintained for 7–14 days.

Clinical characteristics.

Indications.

Pathological conditions caused by corpus luteum insufficiency: threatened miscarriage; primary and secondary amenorrhea; polymenorrhea; dysfunctional uterine bleeding; endometrial hyperplastic processes, endometriosis.

Contraindications. Hypersensitivity to the components of the drug. Second half of pregnancy, ectopic pregnancy or missed abortion, either current or in the patient's history; vaginal bleeding of unknown origin; post-abortion state; hepatic dysfunction, liver disease (hepatitis, cirrhosis); cholestatic jaundice during pregnancy or in medical history; benign hyperbilirubinemia; hepatic failure; renal failure; porphyria; neurological disorders with depressive symptoms; tachycardia; malignant tumors of the breast and genital organs; active venous or arterial thromboembolic disorders, severe thrombophlebitis, or such conditions in medical history.

It is contraindicated for use in diagnosing pregnancy.

Interaction with other medicinal products and other types of interactions. Hydroxyprogesterone caproate reduces the effect of drugs stimulating myometrial contractions (oxytocin, pituitrin), anabolic steroids (retabolil, nerobol), and pituitary gonadotropic hormones. When used concomitantly with oxytocin, the lactogenic effect is diminished. The drug enhances the action of diuretics, antihypertensive agents, immunosuppressants, bromocriptine, and systemic coagulants. It reduces the effectiveness of anticoagulants. It alters the effects of hypoglycemic agents. Gestagenic activity is reduced by microsomal oxidation inducers (carbamazepine, griseofulvin, barbiturates, hydantoins, rifampicin). Combined use of β-adrenergic agonists and hydroxyprogesterone caproate for prevention of preterm labor helps reduce the adverse effects of β-adrenergic agonists.

Hydroxyprogesterone caproate inhibits the metabolism of cyclosporine, leading to increased cyclosporine plasma concentration and risk of toxic effects.

Special precautions.

The medicinal product should be used with caution in patients with arterial hypertension, cardiovascular diseases, diabetes mellitus, bronchial asthma, epilepsy, and migraine.

Use with caution in patients with other conditions predisposing to fluid retention and in those with a history of psychiatric disorders. The drug should be discontinued at the first signs of depression. Patients with a history of psychiatric depression should be closely monitored, and the drug should be withdrawn in cases of severe disease recurrence.

The drug should not be used in patients with rare hereditary disorders such as galactose intolerance, lactase deficiency, or glucose-galactose malabsorption.

Hypersensitivity reactions to progestins have been reported. Hydroxyprogesterone caproate is contraindicated in women with a history of hypersensitivity to progestins.

Progestins may reduce glucose tolerance; therefore, blood glucose levels should be closely monitored in patients with diabetes mellitus. The drug should not be used in cases of unexplained vaginal bleeding (non-functional causes should be considered and appropriate diagnostic measures performed) or in patients with a history of peripheral arterial disease. Careful attention should be paid to early signs and symptoms of thromboembolism during treatment, and therapy should be discontinued if such symptoms occur.

Medication should be suspended and a thorough examination performed if sudden partial or complete vision loss, proptosis, diplopia, or migraine develops. The use of the medicinal product should be discontinued if papilledema or retinal vascular lesions are detected upon examination.

Regular check-ups are recommended during treatment, with frequency and extent determined individually. An initial examination should include breast and pelvic organ examination and a Papanicolaou test.

Patients with any progesterogen-dependent tumor, such as a history of meningioma and/or its progression during pregnancy, or those who have previously received hormonal therapy, require close medical supervision.

Menstruation may cease with prolonged use of high doses.

Pain, swelling, itching, or bruising may occur at the injection site following administration of hydroxyprogesterone caproate. Medical advice should be sought if there is increased discomfort, bleeding or discharge, or inflammatory reaction at the injection site.

The long-term effects of sex hormones on pituitary, ovarian, adrenal, liver, and uterine function require further investigation.

When submitting tissue samples for histological examination, the histologist should be informed that the patient has been receiving progestin therapy.

Use during pregnancy or breastfeeding. The drug should be used only during the first trimester of pregnancy in cases of threatened miscarriage. The risk of congenital anomalies, including genital anomalies in children of both sexes associated with exogenous progesterone exposure during pregnancy, has not been fully established.

Progesterone passes into breast milk; therefore, the drug should not be used during breastfeeding.

Ability to affect reaction speed when driving or operating machinery. The medicinal product may cause visual disturbances and increased fatigue. During treatment, patients should avoid potentially hazardous activities requiring heightened attention and rapid psychomotor responses.

Administration and Dosage

Before use, gently warm the ampoule containing the drug in a water bath (up to 30–40 °C). If crystals have formed, heat the ampoule in boiling water bath until they completely dissolve. Administer intramuscularly or subcutaneously.

In case of threatened or imminent miscarriage during the first trimester of pregnancy, administer 125–250 mg (1–2 mL of a 12.5 % solution) once weekly.

For primary or secondary amenorrhea: administer 250 mg as a single dose or in two divided doses, immediately after discontinuation of estrogenic drugs.

To normalize the menstrual cycle (in cases of polymenorrhea or dysfunctional uterine bleeding), administer the drug at a dose of 65–125 mg (0.5–1 mL of a 2.5 % solution) on days 20–22 of the cycle.

In women under 45 years of age with endometrial hyperplasia (in the absence of hormonally active ovarian tumors), during the first phase of the menstrual cycle, prescribe estrogens (ethinylestradiol 0.05 mg daily from day 5 to day 25 of the cycle) and "Hydroxyprogesterone caproate" 1 mL of a 12.5 % solution once weekly on day 5, 12, and 19 of the cycle for 4–5 cycles. In women aged 45 years and older, administer "Hydroxyprogesterone caproate" 2 mL of a 12.5 % solution once weekly for 6–8 menstrual cycles.

Note: The presence of moisture on the needle or syringe may cause clouding of the solution; however, this does not affect the drug's activity.

Before administration, visually inspect the solution for the presence of solid particles and discoloration, if the solution and packaging permit.

Children. There is no experience with the use of this drug in children; therefore, it should not be used in pediatric practice.

Overdose. When higher doses of the drug are used, adverse effects described in the relevant section occur more frequently. If progestogen-related adverse effects occur, treatment should be discontinued and, after resolution of symptoms, resumed at lower doses. If necessary, symptomatic therapy should be administered.

Side effects.

Cardiovascular system: possible increase in blood pressure, tachycardia, dyspnea, circulatory disorders (myocardial infarction and stroke), severe arterial and venous thromboembolic events, including pulmonary embolism (sometimes fatal).

Metabolic disorders: possible edema, fluid retention, albuminuria, impaired glucose tolerance, changes in plasma lipid profile.

Gastrointestinal system: changes in appetite, bloating, abdominal pain, constipation, diarrhea, liver function disorders and changes in liver function tests, cholestatic jaundice, rarely (with prolonged use) – nausea, vomiting.

Central nervous system (CNS): rarely (with prolonged use) – headache, migraine-type headache, dizziness, depression, insomnia, somnolence, weakness, fatigue, paresthesia, back pain.

Endocrine system: rarely (with prolonged use) – weight gain or weight loss, breast tenderness and tension, changes in vaginal discharge, irregular uterine bleeding, post-treatment anovulation, amenorrhea during or after treatment, oligomenorrhea, menstrual cycle disturbances, premenstrual syndrome, changes in libido, breast discomfort, hirsutism, cystitis.

Genital organs: uterine spasms, disorders of external genital organs such as burning sensation, dryness, genital pruritus, vaginal discharge, increased cervical mucus production, bloody discharge, withdrawal bleeding, breakthrough bleeding, vaginal mycosis.

Immune system: hypersensitivity reactions, anaphylactic reactions, angioedema, urticaria.

Skin and subcutaneous tissue: alopecia, acne, yellow pigmented facial spots (chloasma), allergic skin reactions (rash, pruritus), erythema multiforme.

Eye disorders: visual disturbances, retinal thrombosis, optic neuritis.

General disorders and administration site conditions: fever; injection site reactions, including pain and swelling, abscess.

Effects on the fetus: excessive amounts of progesterone may cause virilization of a female fetus (up to ambiguity of sex).

Progestins may affect the results of the following laboratory tests: liver function (increased sulfobromophthalein retention and other tests); hemostasis system parameters (increased levels of prothrombin and factors VII, VIII, IX, and X); thyroid function tests (increased levels of plasma protein-bound iodine and butanol-extractable iodine, decreased plasma thyroxine-binding capacity).

After therapy with hydroxyprogesterone caproate, several cases of cough, dyspnea, chest tightness, and/or allergy-like reactions have been reported. The likelihood of these adverse effects may increase with higher doses.

Shelf life. 5 years.

Storage conditions. Store in the original packaging to protect from light at a temperature not exceeding 25 °C. Keep out of reach of children.

Incompatibility. The drug must not be mixed with other medicinal products in the same container.

Packaging. 1 ml of the drug in an ampoule. 5 ampoules in a blister pack, 2 blisters in a cardboard box.

Prescription status. Prescription only.

Manufacturer. LLC "FZ "BIOPHARMA", Ukraine.

Manufacturer's address and place of business.
Ukraine, 09100, Kyiv region, Bila Tserkva, Kyivska str., 37.