Medroxyprogesterone-LANS (Suspension) Instructions for Use

Marketing Authorization Holder

Veropharm, LLC (Russia)

ATC Code

G03DA02 (Medroxyprogesterone)

Active Substance

Medroxyprogesterone (Rec.INN registered by WHO)

Dosage Form

Medroxyprogesterone-LANS

Suspension for intramuscular administration 150 mg/1 ml: fl. 3.3 ml or 6.7 ml of 1, 35, 50 or 85 pcs.

Dosage Form, Packaging, and Composition

3.3 ml – vials (1) – carton packs.
6.7 ml – vials (1) – carton packs.
3.3 ml – vials (35) – carton boxes.
3.3 ml – vials (50) – carton boxes.
3.3 ml – vials (85) – carton boxes.
6.7 ml – vials (35) – carton boxes.
6.7 ml – vials (50) – carton boxes.
6.7 ml – vials (85) – carton boxes.

Clinical-Pharmacological Group

Gestagen – depot form

Pharmacotherapeutic Group

Progestogen

Pharmacological Action

Gestagen. It does not possess androgenic or estrogenic activity. It suppresses the secretion of gonadotropic hormones (especially LH). In small doses, it suppresses ovulation. It has an inhibitory effect on the changes necessary for the preparation of the endometrium for the implantation of a fertilized egg and increases the viscosity of the cervical mucus.

In higher doses, it has an antitumor effect in hormone-sensitive malignant neoplasms. This effect is apparently due to the action on steroid hormone receptors and on the pituitary-gonadal system.

Pharmacokinetics

After intramuscular administration of medroxyprogesterone, its release occurs slowly, which ensures the creation of low but constant concentrations in the blood plasma.

The time to reach C_max after intramuscular injection is approximately 4-20 days. Medroxyprogesterone can be detected in the blood plasma 7-9 months after intramuscular injection. T_1/2 after intramuscular administration is 6 weeks.

After oral administration, Medroxyprogesterone is rapidly absorbed from the gastrointestinal tract, C_max in the blood plasma is observed approximately after 2-4 hours. When taken simultaneously with food, the bioavailability of medroxyprogesterone increases, while T_1/2 does not change. T_1/2 after oral administration is from 12 to 17 hours.

The binding of medroxyprogesterone to plasma proteins is about 90-95%.

Medroxyprogesterone penetrates the blood-brain barrier, placental barrier, and is excreted in breast milk.

Medroxyprogesterone is largely metabolized with the participation of cytochrome CYP3A4 in liver microsomes by hydroxylation followed by conjugation. At least 16 metabolites of medroxyprogesterone are currently known. Most of it is excreted through the intestines by biliary secretion.

Indications

For use in gynecology: contraception, endometriosis, vasomotor symptoms in the menopausal period.

For use in oncology: adjuvant and palliative treatment of recurrent and metastatic endometrial cancer or kidney cancer; palliative treatment for hormone-dependent forms of recurrent breast cancer in postmenopausal women; prostate cancer, cancer cachexia in advanced tumors of various locations.

ICD codes

Dosage Regimen

Administer the dosage strictly individually, based on the specific indication, disease stage, and therapeutic protocol.

For contraception, administer a single 150 mg dose via deep intramuscular injection every three months (90 days).

Initiate contraception during the first five days of a normal menstrual cycle or immediately postpartum if not breastfeeding.

For endometriosis, the recommended dose is 50 mg per week or 100 mg every two weeks for at least six months.

For menopausal vasomotor symptoms, administer a 150 mg injection every three months.

In oncology, for endometrial or renal carcinoma, the initial dose ranges from 400 mg to 1000 mg intramuscularly, repeated weekly; upon improvement, use a maintenance dose of 400 mg monthly.

For palliative treatment of breast cancer, administer 500 mg daily for four weeks, then 500 mg twice weekly as maintenance, or use 1000 mg daily initially, reducing to 500 mg twice weekly after four weeks.

For prostate carcinoma, administer 500 mg twice weekly; doses may be reduced to 500 mg per week for maintenance therapy.

For cancer cachexia, a dose of 500 mg daily for the first month is recommended, followed by 500 mg to 1000 mg per week.

Always use a dry syringe and a long, wide-bore needle (21G) for administration.

Shake the vial vigorously immediately before use to ensure a uniform suspension.

Inject deeply into the gluteal muscle; do not administer intravenously.

To minimize discomfort, allow the suspension to reach room temperature before injection.

Rotate injection sites with each subsequent administration.

Adhere to the prescribed intervals between injections to maintain therapeutic efficacy.

Adverse Reactions

From the hematopoietic system: increase in the number of leukocytes and platelets in the blood plasma.

From the endocrine system: Cushing’s syndrome (obesity, moon face, osteoporosis, menstrual cycle disorders, striae of various colors, hirsutism, edema of the lower extremities, decreased sexual function, hyperpigmentation of the skin in friction areas, hypokalemia), decompensation of diabetes mellitus, glucosuria, galactorrhea, decreased glucose tolerance, change in body weight.

From the genitourinary system: change in libido, anorgasmia, dysfunctional uterine bleeding (irregular, heavy, scanty), amenorrhea, change in vaginal discharge, cervical erosion, prolonged anovulation, mastodynia, breast tenderness, lower abdominal pain, vaginitis, increased nipple sensitivity. When used in gynecology – cervical cancer, breast cancer, lack of fertility restoration, unplanned pregnancy, decreased lactation, breast engorgement, breast lumps or bloody discharge from the nipples, galactorrhea, uterine hyperplasia, genitourinary infections, vaginal cysts, lower abdominal pain, vaginal discharge, cervical erosion, prolonged anovulation, mastodynia, increased breast nipple sensitivity, dyspareunia.

From the nervous system: confusion, euphoria, insomnia, drowsiness, depression, dizziness, headache, decreased ability to concentrate, increased nervous excitability, increased fatigue, adrenergic-like reactions (such as hand tremors, sweating, night cramps of the calf muscles), tonic or clonic convulsions; paresthesia, paralysis, facial nerve paralysis.

From the cardiovascular system: stroke, myocardial infarction, chronic heart failure, palpitations, tachycardia, thromboembolic disorders (including pulmonary embolism, deep vein thrombosis of the lower extremities), thrombophlebitis, varicose veins; increased blood pressure, sensation of “hot flashes”.

From the organ of vision: diabetic cataract, visual disturbances, retinal vascular thrombosis.

From the digestive system: constipation, diarrhea, dryness of the oral mucosa, nausea, vomiting, impaired liver function, jaundice, changes in appetite, abdominal pain and discomfort, flatulence, changes in appetite.

From the skin and subcutaneous tissues: acne, alopecia, hirsutism, itching, rash, urticaria.

From the immune system: hypersensitivity reactions (anaphylaxis and anaphylactoid reactions, angioedema).

Other: edema/fluid retention in the body, asthenia, malaise, fainting, hyperthermia, hypercalcemia, back and joint pain; osteoporosis, including osteoporotic bone fractures; shortness of breath, exacerbation of bronchial asthma.

Local reactions: induration at the injection site, skin discoloration at the injection site, sterile abscess.

Contraindications

Hypersensitivity to medroxyprogesterone; pregnancy, breastfeeding period (during the first 6 weeks of the postpartum period); vaginal bleeding of unknown origin; severe liver dysfunction; acute thrombosis and thromboembolism currently (including deep vein thrombosis, pulmonary embolism); migraine; in oncology for oral use – children under 18 years of age, parenterally – age before menarche.

With caution

Thrombophlebitis, thromboembolism or stroke (increased risk or history), epilepsy, bronchial asthma, heart, renal failure, diabetes mellitus, depressive states; patients whose condition may be adversely affected by fluid retention in the body.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

Contraindicated in patients with severe liver dysfunction.

Use in Renal Impairment

Should be used with caution in patients with renal failure.

Pediatric Use

It is necessary to strictly follow the instructions in the instructions for medroxyprogesterone drugs regarding contraindications for use in children by age and the onset of menarche for specific dosage forms of medroxyprogesterone.

Geriatric Use

If it is necessary to use in elderly patients, the risk of exacerbation of chronic diseases should be taken into account.

Special Precautions

Medroxyprogesterone must be used strictly as prescribed and under medical supervision. It is necessary to strictly observe the correspondence of the used dosage form of the drug to the indications for use.

Medroxyprogesterone should be used with particular caution in patients with thrombophlebitis, thromboembolic complications, severe liver dysfunction, hypercalcemia.

When conducting a pathohistological examination of certain organs and tissues, it is necessary to warn the histologist about previous treatment with progestogens. Against the background of the use of medroxyprogesterone, changes in the results of the following studies are possible: determination of the level of gonadotropins; determination of the level of progesterone, cortisol, testosterone (in men), estrogens (in women) in the blood plasma; determination of the level of pregnanediol in the urine; specific sex hormone-binding globulin; glucose tolerance test; metyrapone test.

If dysfunctional uterine bleeding occurs, the patient should be examined to determine the etiology.

During therapy with medroxyprogesterone, it is necessary to carefully monitor the condition of patients who were previously treated for depression.

When treating patients with diabetes mellitus, the ability of medroxyprogesterone to reduce glucose tolerance should be taken into account.

If it is necessary to conduct a cytological or histological examination of the endometrium or cervix, the pathomorphologist should be warned about the ongoing therapy with medroxyprogesterone.

In some patients taking Medroxyprogesterone, suppression of adrenal cortex function (decrease in ACTH and hydrocortisone concentration in blood plasma) has been identified.

When conducting a metyrapone test, it should be taken into account that high doses of medroxyprogesterone used in oncology can cause partial adrenal insufficiency (decreased response of the pituitary-adrenal system), so before administering metyrapone, it is necessary to check the ability of the adrenal cortex to respond to ACTH.

The use of medroxyprogesterone should be interrupted and an examination should be carried out in case of sudden partial or complete loss of vision, or in case of development of exophthalmos, double vision, migraine attacks. If damage to the retinal vessels or edema of the optic disc is detected, treatment with medroxyprogesterone should be discontinued.

The effect of the use of medroxyprogesterone in high doses on bone mineral density (BMD) has not been studied. The decrease in plasma estrogen concentrations caused by the use of medroxyprogesterone leads to a decrease in BMD in women before menopause and may increase the risk of developing osteoporosis in subsequent years of life. All patients using Medroxyprogesterone are recommended to take calcium and vitamin D preparations (in the absence of contraindications), and with long-term use – periodically measure BMD.

Before using medroxyprogesterone for the treatment of gynecological diseases and contraception, treatment of cervical erosion should be carried out. In case of persistent erosion, careful medical supervision is required. Cancer of the genital organs and other organic lesions must be excluded. It is also necessary to conduct a thorough medical examination (including cytological examination of the cervix), paying special attention to such indicators as blood pressure, the condition of the mammary glands, gastrointestinal tract and pelvic organs. If dysfunctional uterine bleeding occurs during the use of medroxyprogesterone, the patient should be examined to exclude malignant neoplasms.

The use of medroxyprogesterone is contraindicated in patients with a removed uterus. The exception is patients who were previously diagnosed with endometriosis.

If the interval between the first and subsequent injection of medroxyprogesterone is more than 13 weeks, then before the next injection, it is necessary to exclude the onset of pregnancy.

In postmenopausal women, estrogen-progestogen therapy should be used in the lowest effective doses and for the shortest possible courses depending on the goals of therapy. In addition, regular assessment of this therapy should be carried out in accordance with the individual characteristics of the patient.

Effect on the ability to drive vehicles and mechanisms

During the use of medroxyprogesterone, dizziness and other adverse reactions from the nervous system, visual disturbances are possible, in connection with which, while taking medroxyprogesterone, caution should be exercised when driving vehicles and other activities that require high concentration and speed of psychomotor reactions.

Drug Interactions

With simultaneous use with aminoglutethimide, a decrease in the concentration of medroxyprogesterone in the blood plasma is possible.

With simultaneous use with drugs that cause induction of liver microsomal enzymes, a decrease in the contraceptive effect of medroxyprogesterone with parenteral use is possible.

Carbamazepine, griseofulvin, phenobarbital, phenytoin, rifampicin may increase the clearance of gestagens (progestogens).

Gestagens (progestogens) may change the effectiveness of hypoglycemic drugs.

Gestagens (progestogens) may inhibit the metabolism of cyclosporine, which leads to an increase in its concentration in the blood plasma and an increased risk of toxicity.

Storage Conditions

Store at 2°C (36°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.