Progestin-cr®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PROGESTIN-KR® (PROGESTINUM-KR)

Composition:

Active substance: 1 g of gel contains: progesterone – 10 mg;

Excipients: macrogol 400; glycerol; 96% ethanol; carbomer; triethanolamine; polyoxyl hydrogenated castor oil; purified water.

Pharmaceutical form. Gel.

Main physicochemical characteristics: colorless or slightly yellowish gel with a characteristic odor.

Pharmacotherapeutic group.

Sex hormones and drugs used in disorders of the genital system.

Progesterone.

ATC code G03D A04.

Pharmacological Properties

Pharmacodynamics

The pharmacological properties are determined by the presence of progesterone, one of the natural hormones in the human body. In breast tissue, progesterone reduces capillary permeability, which is increased under the influence of estrogens. Progesterone participates in the regulation of growth and differentiation of mammary ducts and lobules and blocks the estrogen-induced cycle of rapid mitosis of epithelial cells. Progesterin-KR® is used for the treatment of benign breast diseases developing due to absolute or relative local deficiency of progesterone.

Local application of progesterone significantly increases the activity of 17β-hydroxysteroid dehydrogenase in the mammary gland; this enzyme stimulates the local conversion of estradiol into estrone and contributes to a reduction in estrogen activity in target tissues.

As a result of blocking estrogen receptors, fluid absorption from tissues improves, and compression of mammary ducts decreases.

The thermogenic effect is almost absent due to a different metabolic pathway of progesterone; when applied transdermally, progesterone is converted into alpha-reduced derivatives, unlike orally administered progesterone, which is metabolized into thermogenic beta-reduced derivatives.

By inhibiting tubular reabsorption of sodium ions and increasing cellular filtration, progesterone prevents fluid retention during secretory transformations of the glandular component of mammary glands and, consequently, the development of pain syndrome (mastalgia or mastodynia).

In addition, the action of progesterone is associated with blocking prolactin receptors in breast tissue, leading to a reduction in lactopoiesis.

The transdermal route of progesterone administration also allows influencing the state of glandular epithelium and vascular network, thereby reducing capillary permeability and, consequently, decreasing the degree of breast tissue edema and associated mastalgia symptoms.

Pharmacokinetics

Absorption of progesterone through the skin is approximately 10% of the applied dose, resulting in high drug concentrations (10 times higher than in systemic circulation) in breast tissue without significant entry into the systemic circulation in amounts capable of producing systemic effects, particularly on the uterus.

Studies on serum concentrations of prolactin, estradiol, and progesterone during administration of Progesterin-KR® showed that one hour after application, when maximum absorption into tissues occurs, hormone levels remain practically unchanged.

With transdermal administration, progesterone reaches mammary gland tissues without being destroyed in the liver and without exerting adverse systemic effects on the body.

Secondary metabolism of the drug occurs in the liver, forming conjugates with glucuronic and sulfuric acids. The isoenzyme CYP2C19 is also involved in metabolism. The drug is excreted by the kidneys – 50–60%, and with bile – more than 10%. The amount of metabolites excreted by the kidneys varies depending on the luteal phase.

Clinical characteristics.

Indications.

Mastodynia and benign mastopathies due to progesterone deficiency.

Progestin-KR® is not indicated for use in men.

Contraindications.

Hypersensitivity to any component of the drug.

Breast cancer, nodular forms of fibrocystic mastopathy, tumors (tumor-like formations) of the breast of unknown etiology, genital cancers (as monotherapy).

Interaction with other medicinal products and other types of interactions.

The effect of the drug may be enhanced when used concurrently with combined hormonal contraceptives.

Interaction studies have not been conducted.

According to currently available information, no interactions with other drugs have been observed.

Special precautions for use.

Do not exceed the recommended dose.

Apply the gel after washing, onto dry skin. Use regardless of the day of the menstrual cycle. In case of menstrual cycle disorders, concomitant use with oral progesterone or progestin may be recommended. After application, avoid direct sunlight exposure.

The medicinal product is intended for topical use only — it should not be swallowed.

This medicinal product is NOT A CONTRACEPTIVE.

The possibility of adverse reactions in other individuals upon contact with the patient's skin treated with the medicinal product cannot be ruled out, although this risk has not been specifically studied and has not been reported.

When the skin's barrier function is impaired, there is a risk of progesterone entering the systemic circulation. Therefore, use of the medicinal product in such cases is not recommended.

The medicinal product contains castor oil, which may cause skin reactions.

Use with caution in the following conditions: hepatic insufficiency, renal insufficiency, bronchial asthma, epilepsy, migraine, depression; hyperlipoproteinemia, ectopic pregnancy, abortion, tendency to thrombosis, acute forms of phlebitis and thromboembolic disorders, vaginal bleeding of unknown etiology, porphyria, arterial hypertension, diabetes mellitus.

Use during pregnancy or breastfeeding.

The medicinal product is not indicated for use during pregnancy. There is insufficient experience with the use of the product during pregnancy.

The medicinal product is not indicated for use during breastfeeding. Progesterone may partially pass into breast milk. However, a negative effect on the infant has not been reported.

Ability to influence reaction speed when driving or operating machinery.

No data available.

Method of Administration and Dosage

For external use only. Apply one dose from the applicator (2.5 g of gel) once daily to the surface of each breast and rub in until completely absorbed. The duration of treatment is usually at least 3 months (determined individually by the physician).

Children.

This medicinal product is not intended for use in pediatric practice.

Overdose.

No cases of overdose have been reported. Due to the route of administration, overdose is unlikely.

Menstruation may begin 1–2 days earlier; in such case, the medicinal product can be used from day 10 to day 25 of the cycle. Normal cycle duration will be restored immediately after discontinuation of treatment.

Side effects.

Allergic reactions are possible.

In some cases, menstruation may start 1–2 days earlier, without any changes in the usual monthly volume of discharge. A weak secretory LH-mimetic activity has been observed, which has no common features with the effects of systemic administration of an equivalent dose of progesterone.

When the recommended method of application is followed, systemic absorption of progesterone is unlikely. However, if the skin's barrier function is impaired, there is a risk of developing systemic adverse reactions, including menstrual cycle disorders, amenorrhea, breakthrough bleeding, headache, breast tenderness, hot flushes, metrorrhagia, decreased libido, hypersensitivity reactions (including erythema at the site of gel application), lip and neck swelling, fever, headache, nausea.

Shelf life.

2 years.

Do not use after the expiry date stated on the packaging.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

40 g of gel in a tube No. 1, supplied with a spatula-doser; in a cardboard box.

Prescription status.

By prescription only.

Manufacturer.

JSC "Chempharmplant "Chervona Zirka".

Manufacturer's address and location of business activity.

1 Gordienkovskaya Street, Kharkiv, 61010, Ukraine.