Proginorm gesta

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PROGINORM GESTA

Composition:

Active substance: progesterone;

1 soft capsule contains 100 mg or 200 mg of progesterone;

Excipients: peanut oil, soy lecithin;

capsule shell: gelatin 150 Bloom, glycerol 99%, titanium dioxide (E 171).

Pharmaceutical form. Soft capsules.

Main physicochemical properties: soft, opaque, oval-shaped capsules of almost white color.

Pharmacotherapeutic group.

Sex gland hormones and drugs used in pathologies of the genital system. Progestogens. Pregnane derivatives (4). Progesterone. ATC code G03D A04.

Pharmacological Properties

Pharmacodynamics

The pharmacological properties of PROGINORM GESTA are due to progesterone—one of the hormones of the corpus luteum—which promotes the formation of normal secretory endometrium in women. It induces the transition of the uterine mucosa from the proliferative phase to the secretory phase and, after fertilization, facilitates its transformation into a state necessary for the development of the fertilized ovum. It reduces excitability and contractility of the uterine and tubal musculature. It has no androgenic activity. It exerts a blocking effect on the secretion of hypothalamic factors releasing luteinizing hormone (LH) and follicle-stimulating hormone (FSH), thereby suppressing the pituitary production of gonadotropic hormones and ovulation.

Pharmacokinetics

Absorption

When administered vaginally, progesterone is rapidly absorbed through the mucous membrane. An increase in plasma progesterone levels begins within the first hour, and peak plasma concentrations are reached within 1–3 hours after administration. With the recommended average dose (100 mg of progesterone per night), PROGINORM GESTA enables achieving and maintaining a physiological and stable plasma progesterone level (on average about 9.7 ng/mL), similar to that observed during the luteal phase of a menstrual cycle with normal ovulation.

Thus, PROGINORM GESTA promotes adequate endometrial maturation and facilitates embryo implantation.

With higher doses (above 200 mg per day), progressively increased, the vaginal route of administration allows achieving plasma progesterone levels similar to those observed during the first trimester of pregnancy.

Metabolism

Metabolites in plasma and urine are identical to those formed during the physiological secretion by the ovarian corpus luteum: in plasma, these are mainly 20α-hydroxy, δ4α-pregnanolone and 5α-dihydroprogesterone. Excretion in urine occurs 95% in the form of glucuronide metabolites, the main component being 3α, 5β-pregnanediol (pregnanediol).

Clinical characteristics.

Indications.

Conditions associated with progesterone deficiency.

• Impaired fertility in primary or secondary infertility due to partial or complete luteal phase deficiency (anovulation, luteal phase support during in vitro fertilization preparation, oocyte donation programs). Prevention of habitual or threatened spontaneous abortion in luteal phase deficiency.
• Prevention of preterm birth in women with a short cervix or in women with a history of spontaneous preterm birth.
• Inability or limitations to oral administration of the drug.

Contraindications.

• Hypersensitivity to any component of the drug.
• Severe impairment of liver function.
• Suspected or confirmed neoplasia of the breast or genital organs.
• Undiagnosed vaginal bleeding.
• Failed or incomplete abortion.
• Thrombophlebitis. Thromboembolic disorders.
• Cerebral hemorrhage.
• Porphyria.

Interaction with other medicinal products and other types of interactions.

During estrogen hormone replacement therapy for menopause, it is recommended to administer progesterone no later than day 12 of the cycle.

If PROGINORM GESTA is used in combination with beta-adrenergic agonists for the treatment of preterm labor, the doses of the latter may be reduced.

Concomitant use of other medicinal products may alter progesterone metabolism, leading to increased or decreased plasma progesterone concentrations and consequently altering the drug's effect.

Potent inducers of hepatic enzymes, namely: barbiturates, antiepileptic agents (phenytoin), rifampicin, phenylbutazone, spironolactone, griseofulvin, cause enhanced hepatic metabolism.

Some antibiotics (ampicillins, tetracyclines) may cause changes in intestinal microflora, resulting in altered enterohepatic steroid cycling.

It is known that such drug interactions are individual and may significantly vary among different patient groups; therefore, predicting any clinical manifestations of such interactions is not possible. All progestins may reduce glucose tolerance, which may necessitate an increase in the daily dose of insulin and other antidiabetic agents in patients with diabetes mellitus.

Progesterone bioavailability may be decreased by smoking and increased by alcohol consumption.

Special precautions for use.

Treatment at the recommended doses does not exhibit contraceptive effects.

If treatment is initiated very early in the menstrual cycle, particularly before day 15 of the cycle, shortening of the cycle or breakthrough bleeding may occur.

The drug should not be prescribed in cases of uterine bleeding without first determining the underlying cause, including evaluation of the endometrium.

The medicinal product should be used with caution in patients with fluid retention (e.g., patients with hypertension, cardiovascular or renal disorders, epilepsy, migraine, bronchial asthma), patients with a history of depression, diabetes mellitus, hepatic dysfunction, or photosensitivity.

Prior to prescribing the drug, careful examination is recommended for patients with a family history of tumors, recurrent cholestasis, persistent pruritus during pregnancy, hepatic dysfunction, cardiac or renal insufficiency, fibrocystic mastopathy, epilepsy, asthma, otosclerosis, diabetes mellitus, multiple sclerosis, or systemic lupus erythematosus.

Due to the thromboembolic and metabolic risks, which cannot be completely excluded, treatment should be discontinued if any of the following occur:

• Visual disturbances such as loss of vision, diplopia, retinal vascular lesions, proptosis, or optic disc edema;
• Venous thromboembolic or thrombotic complications, regardless of the affected site;
• Severe headache or migraine.

In case of amenorrhea occurring during treatment, pregnancy should be confirmed or ruled out, as it may be the cause of amenorrhea.

Oily discharge may occur, which is related to the pharmaceutical form of the drug.

More than half of early spontaneous abortions are caused by genetic abnormalities. Infections and mechanical disturbances may also lead to early miscarriages. The only justified indication for progesterone administration would be delayed expulsion of a nonviable embryo. Therefore, progesterone should be prescribed by a physician only in cases of insufficient progesterone secretion.

Before initiating treatment, the patient should undergo a thorough medical and gynecological examination, including vaginal and mammary gland examination and a Papanicolaou smear, taking into account the patient's medical history, contraindications, and precautions. Regular medical check-ups are recommended during treatment. Women receiving hormone replacement therapy (HRT) should carefully evaluate all risks and benefits associated with the therapy.

In postmenopausal women receiving or who have previously received HRT, there is a slight to moderate increase in the likelihood of breast cancer diagnosis. This may be related to earlier diagnosis in patients, the actual effect of HRT, or a combination of both. The risk of breast cancer diagnosis increases with longer duration of treatment and returns to baseline levels approximately five years after discontinuation of HRT. Breast cancer diagnosed in women receiving or who recently received HRT tends to be less invasive than in women who have not undergone HRT. The physician should discuss the increased risk of breast cancer with patients considering long-term hormone therapy, weighing the benefits of HRT.

The medicinal product PROGINORM GESTA contains peanut oil and soy lecithin. This medicinal product should not be used in patients with hypersensitivity to peanuts or soy.

Use during pregnancy or breastfeeding.

Use of PROGINORM GESTA is not contraindicated during pregnancy.

No adverse effects of the drug on the fetus have been observed during its use.

When the drug is used during the second and third trimesters of pregnancy, liver function should be monitored.

Excretion of progesterone into breast milk has not been thoroughly studied. Therefore, its use should be avoided during breastfeeding.

There is evidence suggesting a possible risk of hypospadias when progestogens are used during pregnancy for prevention of habitual abortion or threatened miscarriage due to luteal phase deficiency. Patients should be informed about this potential risk.

Ability to influence reaction speed when driving or operating machinery.

The use of PROGINORM GESTA has negligible influence on the ability to drive vehicles or operate machinery.

Method of Administration and Dosage

The duration of treatment depends on the nature of the disease.

Capsules should be inserted deeply into the vagina while lying on the back.

Before each application, hands must be thoroughly washed to ensure no residue of soap or cleaning agent remains.

The average dose is 200 mg of progesterone per day (1 capsule of 200 mg or 2 capsules of 100 mg, divided into two doses administered in the morning and evening, inserted deeply into the vagina, if necessary with the aid of an applicator). The dose may be increased depending on the patient's response.

• Partial luteal phase deficiency (anovulation, menstrual cycle disorders): the daily dose is 200 mg for 10 days (usually from day 17 to day 26 of the cycle).
• Complete luteal phase deficiency [complete absence of progesterone in women with non-functioning (absent) ovaries (oocyte donation)]: the progesterone dose is 100 mg on days 13 and 14 of the transfer cycle. From day 15 to day 25 of the cycle, the progesterone dose is 200 mg, divided into two doses (morning and evening). Starting from day 26, in case of early pregnancy diagnosis, the dose is gradually increased (each week) by 100 mg of progesterone per day, reaching a maximum of 600 mg of progesterone per day, divided into three doses. This dosage should be maintained until day 60.
• Luteal phase support during in vitro fertilization (IVF) cycles: treatment begins on the evening of embryo transfer day, at a dose of 600 mg per day administered in three doses (200 mg every 8 hours).
• In cases of threatened miscarriage or for prevention of recurrent miscarriages due to luteal insufficiency: 200–400 mg per day (100–200 mg per dose every 12 hours) up to 12 weeks of gestation.
• Prevention of preterm birth in women with a short cervix or in women with a history of spontaneous preterm birth: the dose is 200 mg per day administered in the evening before bedtime from week 22 to week 36 of pregnancy.

Children

The drug is not intended for use in pediatric practice.

Overdose

Symptoms of overdose may include adverse reactions such as drowsiness, dizziness, euphoria, dysmenorrhea, shortened cycle duration, and metrorrhagia.

In some individuals, the usual dose may be excessive due to existing or secondary unstable endogenous progesterone secretion, increased sensitivity to the drug, or very low concomitant serum estradiol levels.

In such cases, the following measures are sufficient:

• reduce the progesterone dose or administer progesterone in the evening before bedtime for 10 days per cycle if drowsiness or dizziness occurs, which quickly resolves;
• delay the start of treatment to a later point in the cycle (e.g., day 19 instead of day 17) if cycle shortening or bleeding occurs;
• verify whether the patient receiving HRT in the premenopausal period has adequate estradiol levels.

Side effects.

The following adverse reactions have been observed with oral administration:

Other adverse reactions may also occur, such as changes in libido, breast discomfort, premenstrual symptoms, hyperthermia, insomnia, alopecia, hirsutism, venous thromboembolism, pulmonary artery embolism, fluid retention, changes in body weight, gastrointestinal disorders, and anaphylactic reactions.

Somnolence and/or brief episodes of dizziness may occur, particularly in cases of concomitant hypoestrogenism. Reducing the dose of the drug or increasing the estrogen dose promptly eliminates these symptoms without diminishing the therapeutic effect.

If treatment is initiated very early in the menstrual cycle, especially before day 15, shortened cycles or breakthrough bleeding may occur.

With vaginal administration of progesterone, hypersensitivity reactions may occur, including burning, itching, hyperemia, and oily discharge.

Shelf life. 3 years.

Storage conditions.

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

Keep out of reach of children.

Packaging.

15 soft capsules in a blister; 2 blisters per carton.

Prescription status.

Prescription only.

Manufacturer.

LABORATORIOS LEON FARMA S.A.

Manufacturer's address and place of business.

Polígono Industrial Navatejera, Calle La Valiña s/n, Villacarralde, 24193 León, Spain.

Marketing Authorization Holder.

JSC "Farmliga" / UAB “Farmlyga”.

Address of the Marketing Authorization Holder.

Antakalnio g. 48A-304, Vilnius, Republic of Lithuania.