Progesterone

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PROGESTERON (PROGESTERON)

Composition:

Active substance: progesterone;

1 g of gel contains progesterone — 10 mg;

Excipients: carbomer; 96% ethanol; diethylamine; polyoxyl hydrogenated castor oil; octyldodecanol; purified water.

Pharmaceutical form. Gel.

Main physicochemical properties: colorless, slightly opalescent semi-transparent gel with an alcoholic odor.

Pharmacotherapeutic group. Sex gland hormones and drugs used in pathologies of the reproductive system. Progestogens. Pregnane derivatives.

ATC code G03DA04.

Pharmacological Properties

Pharmacodynamics

The active ingredient of the medicinal product, progesterone, is one of the natural hormones of the human body. In mammary gland tissues, progesterone reduces capillary permeability, which increases 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. Progesterone is used for the treatment of benign breast disorders developing due to absolute or relative local progesterone deficiency.

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

As a result of estrogen receptor blockade, fluid absorption from tissues improves, and pressure on 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 blockade of prolactin receptors in mammary gland tissues, leading to reduced lactopoeisis.

Transdermal administration of progesterone also affects the condition of glandular epithelium and vascular network, resulting in reduced capillary permeability, and thus decreased 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 concentration (10 times higher than in systemic circulation) in mammary gland tissues without significant entry into systemic circulation in amounts capable of producing systemic effects, especially on the uterus.

Studies on serum concentrations of prolactin, estradiol, and progesterone during treatment with Progesterone gel showed that one hour after application, when maximum absorption into tissues occurs, hormone levels remain practically unchanged.

With transdermal application, 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 also participates in metabolism. The drug is excreted by the kidneys — 50–60%, with bile — more than 10%. The amount of metabolites excreted by the kidneys varies depending on the luteal phase.

Clinical characteristics.

Indications.

Benign breast diseases:

• essential mastodynia;
• mastodynia associated with benign breast disease (complex treatment of benign mastopathy against the background of progesterone deficiency).

Progesterone is not indicated for use in men.

Contraindications.

Hypersensitivity to any component of the drug.

Breast cancer.

Nodular forms of fibrocystic mastopathy.

Breast tumors (tumor-like formations) of unclear etiology.

Genital cancers (as monotherapy).

Interaction with other medicinal products and other forms of interactions.

The effect of the drug may be enhanced when used 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.

The breasts and hands must be completely clean during application. In case of menstrual cycle disorders, concomitant use with oral progesterone or progestin may be recommended.

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

THIS MEDICINAL PRODUCT IS NOT A CONTRACEPTIVE.

The risk of adverse reactions in other individuals upon skin contact with the patient's skin where the medicinal product has been applied has not been specifically studied and has not been reported, but cannot be excluded.

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

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 or thromboembolic disorders, vaginal bleeding of unknown origin, porphyria, arterial hypertension, diabetes mellitus.

Avoid exposure to direct sunlight after application of the gel.

Use during pregnancy or breastfeeding.

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

Progesterone is not indicated for use during breastfeeding. Progesterone may be partially excreted in breast milk. However, a negative effect on the infant has not been described.

Ability to influence reaction speed when driving vehicles or operating machinery.

Data are lacking.

Method of Administration and Dosage

For transdermal use.

Treatment should be continuous throughout the month, including during menstruation, with daily application of the medicinal product.

The treatment course is determined by the physician; typically, the average duration of treatment is from 3 to 6 months.

The maximum daily dose is 5 g.

Pressing on the lower part of the tube, squeeze out the gel dose into the groove of the dosing spatula.

Apply one or two doses (2.5 g) of the gel onto clean, dry skin of each breast using the dosing spatula. Gently rub in until the medicinal product is completely absorbed into the skin.

Children

The medicinal product is not used in pediatric practice.

Overdose

No cases of overdose have been reported.

Due to the method of administration, overdose is unlikely.

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

Side effects.

Isolated cases of hypersensitivity or non-specific skin irritation have been reported.

In some cases, menstruation may start one to two days earlier without any changes in the usual monthly volume of discharge. A weak secretory LH-mimetic activity has been observed, which does not share characteristics with the effects of systemic administration of an equivalent dose of progesterone.

When the recommended route of administration is followed, systemic absorption of progesterone is unlikely. However, if the skin barrier function is impaired, there is a risk of developing systemic adverse reactions, including menstrual cycle disturbances, amenorrhea, breakthrough bleeding, and headache.

Very rarely: breast tenderness, hot flushes, metrorrhagia, decreased libido, hypersensitivity reactions including erythema at the site of gel application, swelling of the lips and neck, fever, headache, nausea.

Reporting of suspected adverse reactions.

Following marketing authorization of the medicinal product, it is important to collect reports of suspected adverse reactions. This allows ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report suspected adverse reactions through the national pharmacovigilance system.

Shelf life. 2 years.

Do not use after the expiry date.

Storage conditions.

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

Keep out of reach and sight of children.

Packaging. 40 g of gel in aluminum tubes. One tube in a set with a spatula-doser and instructions for medical use in a cardboard box.

80 g of gel in aluminum tubes. One tube in a set with a spatula-doser and instructions for medical use in a cardboard box.

Prescription category. Prescription only.

Manufacturer.

JSC "CHEMICAL PHARMACEUTICAL PLANT "CHERVONA ZIRKA".

Manufacturer's address and location of operations.

1, Gordienkivska Street, Kharkiv, Kharkiv region, 61010, Ukraine.