Proginorm ovo

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT PROGINORM OVO

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, glycerin 99 %, titanium dioxide (E 171).

Pharmaceutical form. Soft capsules.

Main physico-chemical properties: soft, opaque, almost white, oval-shaped capsules.

Pharmacotherapeutic group.

Sex hormones and drugs used in pathologies of the reproductive system. Progestogens. Pregnane derivatives (4). Progesterone. ATC code G03DA04.

Pharmacological Properties

Pharmacodynamics

The pharmacological properties of PROGINORM OVO 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 fallopian tube musculature. It has no androgenic activity. It exerts an inhibitory effect on the hypothalamic release of LH and FSH factors, suppresses pituitary gonadotropin hormone production and ovulation.

Pharmacokinetics

Absorption

An increase in plasma progesterone levels is observed from the first hour after absorption of the drug in the gastrointestinal tract. The highest plasma progesterone levels occur 1–3 hours after administration (1 hour – 4.25 ng/mL, 2 hours – 11.75 ng/mL, 4 hours – 8.37 ng/mL, 6 hours – 2 ng/mL, and 1.64 ng/mL at 8 hours).

Metabolism

The main metabolites of progesterone in plasma are 20α-hydroxy, δ4α-pregnanolone, and 5α-dihydroprogesterone. The drug is excreted in urine as glucuronide metabolites, the main one being 3α,5β-pregnanediol (pregnanediol). These metabolites are identical to those found during physiological secretion by the ovarian corpus luteum.

Clinical characteristics.

Indications.

Gynecological:

1. Conditions associated with progesterone deficiency, namely:
   • premenstrual syndrome;
   • menstrual cycle disorders (dysovulation, anovulation);
   • fibrocystic mastopathy;
   • premenopausal period.
2. Hormone replacement therapy in menopause (in combination with estrogen therapy).
3. Infertility due to luteal phase deficiency.

Obstetrical:

1. Prevention of habitual or threatened miscarriage due to luteal phase deficiency.
2. Threat of preterm labor.

Contraindications.

• Hypersensitivity to any component of the drug.
• Severe hepatic dysfunction.
• Suspected or confirmed neoplasms 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 forms of interaction.

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

If Proginorm Ovum 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 drugs may alter progesterone metabolism, causing an increase or decrease in plasma progesterone concentration and, consequently, lead to changes in drug effect.

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

Some antibiotics (ampicillins, tetracyclines) may alter intestinal microflora, resulting in changes to the enterohepatic steroid cycle.

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

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

Special precautions for use

Treatment at recommended doses does not have a contraceptive effect.

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

The drug should not be administered in cases of uterine bleeding without prior investigation of the underlying cause, including endometrial examination.

Use with caution in patients with fluid retention (e.g., hypertension, cardiovascular, renal or hepatic disorders), in patients with epilepsy, migraine, bronchial asthma, history of depression, diabetes mellitus, hepatic dysfunction, or photosensitivity.

Prior to initiating treatment, patients with a family history of tumors, or with 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 should be carefully evaluated.

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

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

In the event of amenorrhea during treatment, pregnancy should be confirmed or excluded, as it may be the cause of amenorrhea.

More than half of early spontaneous abortions are due to genetic abnormalities. In addition, infectious conditions and mechanical disturbances may also cause early miscarriages. The only justified indication for progesterone administration would be delayed expulsion of a nonviable gestational sac. Therefore, progesterone should be prescribed by a physician only in cases of documented progesterone deficiency.

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

In postmenopausal women receiving or who have previously received HRT, there is a weak to moderate increase in the likelihood of breast cancer diagnosis. This may be related to earlier diagnosis in these patients, a true effect of HRT, or a combination of both. The risk of breast cancer diagnosis increases with duration of treatment and returns to baseline levels within 5 years after discontinuation of HRT. Breast cancers diagnosed in women receiving or who have recently received HRT tend to be less invasive than those in untreated women. The physician should discuss the increased risk of breast cancer with patients considering long-term hormone therapy, carefully weighing the benefits of HRT.

The drug should not be taken with food, but should be taken at bedtime. Concurrent food intake increases the bioavailability of the drug.

This medicinal product contains peanut oil and soy lecithin. If the patient is allergic to peanuts or soy, the medicinal product PROGINORM OVO should not be used.

Use during pregnancy or breastfeeding

Use of PROGINORM OVO is not contraindicated during pregnancy, including the first weeks (see section "Indications" (Obstetrical indications)).

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 are data suggesting a possible risk of hypospadias with the use of progestogens during pregnancy for prevention of habitual abortion or threatened miscarriage due to luteal phase deficiency. Patients should be informed about this potential risk.

Effect on the ability to drive or operate machinery

Drivers and machine operators: drowsiness and dizziness may occur following oral administration of the drug.

Administration of the capsules at bedtime may help avoid these adverse effects.

Cases of drowsiness and dizziness have been reported only with oral administration of progesterone.

Method of Administration and Dosage

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

It is recommended to take capsules with a glass of water on an empty stomach, preferably in the evening before bedtime.

In most cases, the daily dose is 200–300 mg administered in 1 or 2 doses (200 mg in the evening before bedtime, and 100 mg in the morning if necessary).

• For luteal phase deficiency (premenstrual syndrome, menstrual cycle disorders, perimenopause, fibrocystic mastopathy): take for 10 consecutive days (usually from day 17 to day 26 of the cycle inclusive).
• For menopausal hormone therapy: since estrogen therapy alone is not recommended, progesterone must be added as a supplement during the last 2 weeks of each treatment cycle, following a one-week supportive therapy, during which withdrawal bleeding may occur.
• For threatened preterm labor: administer 400 mg of PROGINORM OVO every 6–8 hours until symptoms resolve. The effective dose and frequency should be individually adjusted according to clinical manifestations of threatened preterm labor. After symptom resolution, the dose of PROGINORM OVO should be gradually reduced to a maintenance dose (e.g., 200 mg three times daily). This maintenance dose may be continued up to 36 weeks of gestation.

The use of progesterone after 36 weeks of pregnancy is not recommended.

Children. The drug is not intended for use in pediatric practice.

Overdose

Symptoms of overdose may manifest as an exacerbation of adverse reactions, including drowsiness, dizziness, euphoria, dysmenorrhea, shortened cycle length, and metrorrhagia.

In some individuals, the standard dose may be excessive due to existing or secondary unstable endogenous progesterone secretion, increased sensitivity to the drug, or very low concomitant blood 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 transient dizziness occurs;
• 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 during perimenopause has sufficient estradiol levels.

Adverse reactions.

The following phenomena have been observed:

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

Somnolence and/or brief episodes of dizziness are particularly observed in cases of concomitant hypoestrogenism. Reducing the dose of the drug or increasing the estrogen dose promptly resolves these symptoms without diminishing the therapeutic effect.

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

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.

By prescription only.

Manufacturer.

LABORATORIOS LEON FARMA, S.A.

Manufacturer's address and location of operations.

Polígono Industrial Navatejera, Calle La Valina s/n, Villacilambre, 24193 León, Spain.

Marketing Authorization Holder.

JSC "Farmliga" / UAB “Farmlyga”.

Address of the Marketing Authorization Holder.

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