Vanel (Capsules) Instructions for Use

Marketing Authorization Holder

Zentiva, k.s. (Czech Republic)

Manufactured By

Laboratorios Leon Farma, S.A. (Spain)

ATC Code

G03DA04 (Progesterone)

Active Substance

Progesterone (Rec.INN registered by WHO)

Dosage Forms

	Vanel	Capsules 100 mg: 15, 30 or 90 pcs.
		Capsules 200 mg: 15, 30 or 90 pcs.

Dosage Form, Packaging, and Composition

Capsules soft gelatin, egg-shaped, white with a yellowish-brownish tint, containing a thick suspension of almost white color.

Excipients: peanut oil – 149 mg, soy lecithin – 1 mg.

Capsule shell composition: gelatin – 77.7 mg, glycerol – 31.5 mg, titanium dioxide (E171) – 0.9 mg.

15 pcs. – blisters (1) – cardboard packs.
15 pcs. – blisters (2) – cardboard packs.
15 pcs. – blisters (6) – cardboard packs.

Capsules soft gelatin, egg-shaped, white with a yellowish-brownish tint, containing a thick suspension of almost white color.

Excipients: peanut oil – 298 mg, soy lecithin – 2 mg.

Capsule shell composition: gelatin – 158.9 mg, glycerol – 64.3 mg, titanium dioxide (E171) – 1.8 mg.

15 pcs. – blisters (1) – cardboard packs.
15 pcs. – blisters (2) – cardboard packs.
15 pcs. – blisters (6) – cardboard packs.

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, to 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 muscles and fallopian tubes. 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 oral administration, Progesterone is well absorbed from the gastrointestinal tract. With intravaginal administration, absorption occurs rapidly. The C_max of progesterone in blood plasma is reached 2-6 hours after administration. When administered in doses greater than 200 mg/day, the progesterone concentration corresponds to the first trimester of pregnancy.

The main metabolites determined in blood plasma are 20-alpha-hydroxy-delta-4-alpha-pregnanolone and 5-alpha-dihydroprogesterone. It is excreted in the urine as metabolites, 95% of which are glucuronoconjugated metabolites, mainly 3-alpha, 5-beta-pregnanediol (pregnanediol). These metabolites, which are determined in blood plasma and urine, are similar to substances formed during the physiological secretion of the corpus luteum. Plasma protein binding is 90%. Progesterone accumulates in the uterus. It is excreted in the urine as metabolites, the main part being 3-alpha, 5-beta-pregnanediol (pregnanediol).

Indications

Progesterone-deficient conditions in women.

Orally: threatened abortion or prevention of habitual abortion due to progesterone insufficiency; infertility due to luteal insufficiency; premenstrual syndrome; menstrual cycle disorders due to impaired ovulation or anovulation; fibrocystic mastopathy; menopausal transition period; menopausal (replacement) hormone therapy (MHT) in peri- and postmenopause (in combination with estrogen-containing drugs).

Vaginally: MHT in case of progesterone deficiency with non-functioning (absent) ovaries (egg donation); prevention of preterm birth in women at risk (with shortened cervix and/or history of preterm birth and/or premature rupture of membranes); luteal phase support during preparation for in vitro fertilization; luteal phase support in a spontaneous or induced menstrual cycle; premature menopause; MHT (in combination with estrogen-containing drugs); infertility due to luteal insufficiency; threatened abortion or prevention of habitual abortion due to progesterone insufficiency.

ICD codes

Dosage Regimen

Administer orally or intravaginally as directed for the specific indication.

For oral administration, take in the evening to mitigate central nervous system effects such as drowsiness and dizziness. Swallow capsules whole with water. Do not take with food, as this increases bioavailability.

For intravaginal administration, insert the capsule deeply into the vagina. Avoid concurrent use of other intravaginal products to prevent impaired absorption.

For infertility due to luteal insufficiency, administer 200-300 mg per day in divided doses (100 mg two or three times daily) for 10-12 days.

For threatened or habitual abortion due to progesterone deficiency, administer 200-600 mg per day in divided doses until symptoms resolve.

For premenstrual syndrome and menstrual cycle disorders, administer 200-400 mg daily from the 17th to the 26th day of the cycle.

For menopausal hormone therapy in combination with an estrogen, administer 200 mg daily for the last 12-14 days of each estrogen cycle.

For luteal phase support during in vitro fertilization, intravaginal administration of 600 mg per day in divided doses is typical, starting after oocyte retrieval.

For prevention of preterm birth in at-risk women, the intravaginal dose is 200 mg at bedtime, starting from the 22nd to 24th week and continuing until week 36.

Adjust dosage individually based on clinical response and tolerability. Discontinue treatment if acyclic bleeding occurs until its cause is determined. Monitor patients with a history of depression closely.

Adverse Reactions

From the reproductive system and mammary glands: frequently – menstrual cycle disorders, amenorrhea, acyclic bleeding; infrequently – mastodynia.

From the psyche: very rarely – depression.

From the nervous system: frequently – headache; infrequently – drowsiness, transient dizziness.

From the gastrointestinal tract: frequently – abdominal bloating; infrequently – vomiting, diarrhea, constipation; rarely – nausea.

From the liver and biliary tract: infrequently – cholestatic jaundice.

Allergic reactions: very rarely – urticaria.

From the skin and subcutaneous tissues: infrequently – itching, acne; very rarely – chloasma.

With intravaginal application, drowsiness and dizziness were not observed.

Contraindications

Deep vein thrombosis, thrombophlebitis; thromboembolic disorders (pulmonary embolism, myocardial infarction, stroke), intracranial hemorrhage or a history of these conditions/diseases; vaginal bleeding of unknown 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; age under 18 years (efficacy and safety not established); breastfeeding period; 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; II and III trimesters of pregnancy.

Use in Pregnancy and Lactation

Use with caution in the II and III trimesters of pregnancy due to the risk of cholestasis.

Progesterone penetrates into breast milk, therefore use is contraindicated during breastfeeding.

Use in Hepatic Impairment

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 the drug with caution in chronic renal failure.

Pediatric Use

Contraindicated in children under 18 years of age (efficacy and safety not established).

Special Precautions

Not intended for use as a contraceptive.

Do not take orally with food, as food intake increases the bioavailability of progesterone.

Use with caution in diseases and conditions that may be aggravated by fluid retention.

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

With long-term treatment with progesterone, regular medical examinations (including liver function tests) are necessary; treatment should be discontinued if abnormalities in liver function tests or cholestatic jaundice occur.

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

If amenorrhea occurs during treatment, pregnancy must be excluded.

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

Patients with a history of chloasma or a tendency to develop it are advised to avoid UV radiation.

The use of progesterone to prevent threatened abortion is justified only in cases of progesterone deficiency.

Due to the risk of thromboembolic complications, the use of the drug 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 supervision.

When using progesterone with estrogen-containing drugs, it is necessary to refer to their instructions for use regarding the risks of venous thromboembolism.

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

Effect on ability to drive vehicles and operate machinery

When using the drug orally, caution must be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

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

It 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 as a result of 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.

With intravaginal use, simultaneous use of other intravaginally applied medicinal products should be avoided to prevent impairment of the release and absorption of progesterone.

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.