Progesterone (Solution) Instructions for Use

ATC Code

G03DA04 (Progesterone)

Active Substance

Progesterone (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Gestagen

Pharmacotherapeutic Group

Sex hormones and modulators of the genital system; gestagens; pregn-4-ene derivatives

Pharmacological Action

A hormone identical to the natural hormone of the corpus luteum of the ovary. By binding to receptors on the surface of target organ cells, it penetrates the nucleus where, by activating DNA, it stimulates RNA synthesis.

It promotes the transition of the uterine mucosa from the proliferation phase, induced by the follicular hormone estradiol, into the secretory phase. After fertilization, it promotes the transition to the state necessary for the development of the fertilized egg. It reduces the excitability and contractility of the uterine and fallopian tube muscles. It promotes the formation of a normal endometrium. It stimulates the development of the terminal elements of the mammary gland and induces lactation.

By stimulating protein lipase, it increases fat reserves and increases glucose utilization. By increasing the concentration of basal and stimulated insulin, it promotes the accumulation of glycogen in the liver, increases the production of pituitary gonadotropic hormones; reduces azotemia, increases nitrogen excretion in the urine.

Pharmacokinetics

After intramuscular administration, it is absorbed rapidly and almost completely. After intramuscular administration of 10 mg of progesterone, the C_max in plasma is reached within approximately 8 hours and remains above the basal level for about 24 hours.

Progesterone actively binds to plasma proteins, mainly to albumin (50-54%) and corticosteroid-binding globulin (43-48%). It is metabolized in the liver to form metabolites – pregnanediol and pregnanolone, which conjugate with glucuronic and sulfuric acids. The isoenzyme CYP2C19 is involved in the metabolism. Progesterone metabolites are excreted by the kidneys – 50-60%, through the intestine – more than 10%. The amount of metabolites excreted by the kidneys varies depending on the corpus luteum phase. T_1/2 – several minutes.

Indications

Infertility due to corpus luteum insufficiency.

ICD codes

Dosage Regimen

Administer the solution by intramuscular injection only.

The standard therapeutic dose is 12.5 mg administered once daily.

Initiate treatment precisely from the confirmed moment of ovulation.

Continue daily administration for a duration of two weeks.

Do not exceed the prescribed daily dose or treatment duration.

Adhere strictly to the prescribed regimen for the full course of therapy.

Discontinue use and consult a physician if pregnancy is confirmed during treatment.

Rotate injection sites to minimize local irritation and tissue damage.

Use aseptic technique for every injection to prevent infection.

Adverse Reactions

From the immune system skin itching, rash, urticaria, anaphylactoid reactions.

From the endocrine system hirsutism.

From the metabolism edema, increase or decrease in body weight, decreased appetite, hyperthermia.

From the psyche apathy, dysphoria, depression, mood lability.

From the nervous system headache, dizziness, drowsiness, insomnia, asthenia, optic neuritis.

From the organ of vision visual impairment.

From the vessels increased blood pressure, thromboembolism (including pulmonary embolism), thrombosis of cerebral vessels or retinal veins, thrombophlebitis, hemorrhagic rash.

From the digestive system nausea, vomiting, abdominal bloating, constipation, diarrhea, abdominal pain.

From the liver and biliary tract cholecystitis, cholestatic jaundice, cholestatic hepatitis.

From the genital organs and mammary gland change in libido; breakthrough bleeding; spotting; amenorrhea; shortening of the menstrual cycle; cervical erosion; spasm of the uterine muscles, vaginal discharge, itching and discomfort in the vagina, vulvovaginitis, ovarian hyperstimulation syndrome, hot flashes, malignant diseases of the mammary gland; change in the viscosity of cervical secretion; premenstrual syndrome; galactorrhea; enlargement, pain and tension of the mammary glands.

From the musculoskeletal system back pain.

From the skin and subcutaneous tissues acne, alopecia, multiforme erythema, nodular erythema.

From the urinary system cystitis.

General reactions : general malaise, fatigue

Local reactions hyperemia, irritation and/or pain at the injection site, hematoma, induration, swelling and itching at the injection site.

Contraindications

Deep vein thrombosis, thrombophlebitis; thromboembolic disorders (pulmonary embolism, myocardial infarction, stroke), intracranial hemorrhage or a history of these conditions/diseases; vaginal bleeding of unclear origin; incomplete abortion; porphyria; established or suspected malignant neoplasms of the mammary glands and genital organs; severe liver diseases (including cholestatic jaundice, hepatitis, Dubin-Johnson syndrome, Rotor syndrome, malignant liver tumors) currently or in history; idiopathic jaundice, itching or herpes during a previous pregnancy; pregnancy, breastfeeding period; age under 18 years (efficacy and safety not established); hypersensitivity to progesterone.

With caution

Diseases of the cardiovascular system, arterial hypertension, chronic renal failure, diabetes mellitus, bronchial asthma, epilepsy, migraine, depression, hyperlipoproteinemia, mild to moderate liver dysfunction, photosensitivity.

Use in Pregnancy and Lactation

Use is contraindicated during pregnancy and breastfeeding.

Use in Hepatic Impairment

Use is contraindicated in severe liver diseases (including cholestatic jaundice, hepatitis, Dubin-Johnson syndrome, Rotor syndrome, malignant liver tumors) currently or in history.

Use with caution in mild to moderate liver dysfunction.

Use in Renal Impairment

Use with caution in chronic renal failure.

Pediatric Use

Use is contraindicated under the age of 18 years (efficacy and safety have not been established).

Geriatric Use

Efficacy and safety in elderly patients (over 65 years) have not been established. There are no indications for use in old age.

Special Precautions

Not used for contraception.

Before starting the use of progesterone, a medical examination is necessary, including an examination of the mammary glands and pelvic organs and a Pap smear.

Should be used with caution in patients with diseases and conditions that may be aggravated by fluid retention (arterial hypertension, cardiovascular diseases, chronic renal failure, epilepsy, migraine, bronchial asthma); in patients with diabetes mellitus; mild to moderate liver dysfunction; photosensitivity.

Patients with a history of depression should be monitored, and in case of severe depression, Progesterone should be discontinued.

Patients with concomitant cardiovascular diseases or a history of them should also be periodically observed by a doctor.

With long-term treatment with progesterone, regular medical examinations are necessary (including liver function tests); treatment should be discontinued in case of deviations from normal liver function tests or cholestatic jaundice.

When using progesterone, a decrease in glucose tolerance and an increased need for insulin and other hypoglycemic drugs in patients with diabetes mellitus is possible.

If amenorrhea occurs during treatment, pregnancy must be ruled out.

In case of acyclic bleeding, Progesterone should not be used until their cause is clarified, including a histological examination of the endometrium.

In patients with a history of chloasma or a tendency to develop it, it is recommended to avoid UV radiation.

Due to the risk of thromboembolic complications, the use of progesterone should be discontinued in case of occurrence: visual disturbances, such as loss of vision, exophthalmos, double vision, vascular lesions of the retina; migraine; venous thromboembolism or thrombotic complications, regardless of their location.

If there is a history of thrombophlebitis, the patient should be under close observation.

The use of progesterone may affect the results of some laboratory tests, including liver function indicators, thyroid function; coagulation parameters; pregnanediol concentration.

Effect on ability to drive vehicles and mechanisms

During treatment, caution should be exercised when driving vehicles, mechanisms, or engaging in activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Progesterone enhances the effect of diuretics, antihypertensive drugs, immunosuppressants, anticoagulants.

Reduces the lactogenic effect of oxytocin.

Concomitant use with inducers of hepatic microsomal enzymes CYP3A4, such as barbiturates, antiepileptic drugs (phenytoin), rifampicin, phenylbutazone, spironolactone, griseofulvin, is accompanied by an acceleration of progesterone metabolism in the liver.

Concomitant administration of progesterone with some antibiotics (penicillins, tetracyclines) may lead to a decrease in its effectiveness due to disruption of the enterohepatic recirculation of sex hormones due to changes in the intestinal microflora.

The severity of these interactions may vary among different patients, so predicting the clinical effects of the listed interactions is difficult.

Ketoconazole may increase the bioavailability of progesterone.

Progesterone may increase the concentration of ketoconazole and cyclosporine.

Progesterone may reduce the effectiveness of bromocriptine.

Progesterone may cause a decrease in glucose tolerance, consequently increasing the need for insulin or other hypoglycemic drugs in patients with diabetes mellitus.

The bioavailability of progesterone may be reduced in smoking patients and with excessive alcohol consumption.

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.