Utrogestan

UTROGESTAN VAGINAL 200MG CAPSULES

Each capsule contains 200 mg progesterone (micronised).

Excipients with known effect: Soya lecithin

For a full list of excipients, see Section 6.1.

Vaginal Capsules, soft

Ovoid and slightly yellow soft capsules, containing whitish oily suspension.

Utrogestan Vaginal 200 mg Capsules is indicated in women for

- Supplementation of the luteal phase during Assisted Reproductive Technology (ART) cycles.

- Prevention of preterm birth in women with a singleton pregnancy who have a short cervix (mid-trimester sonographic cervix ≤25 mm) and/or a history of spontaneous preterm birth

Posology

For supplementation of the luteal phase during Assisted Reproductive Technology cycles - the recommended dosage is 600 mg/day, in three divided doses, from the day of embryo transfer until at least the 7^th week of pregnancy and not later than the 12^th week of pregnancy.

For prevention of preterm birth in women with a singleton pregnancy who have a short cervix and/or a history of spontaneous preterm birth, the recommended dosage is 200 mg per day in the evening at bedtime from around week 20 to week 34 of pregnancy.

Paediatric population

There is no relevant use of Utrogestan Vaginal 200 mg Capsules in the paediatric population.

Older people

There is no relevant use of Utrogestan Vaginal 200 mg Capsules in older people.

Method of Administration:

Vaginal

Each capsule of Utrogestan Vaginal 200mg must be inserted deep into the vagina.

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1,

• Severe hepatic dysfunction,

• Undiagnosed vaginal bleeding,

• Mammary or genital tract carcinoma,

• Thrombophlebitis,

• Thromboembolic disorders,

• Cerebral haemorrhage,

• Porphyria.

• Missed abortion

Warnings:

Utrogestan Vaginal 200mg Capsules should only be used during the first three months of pregnancy and must only be administrated by vaginal route.

Utrogestan Vaginal 200mg Capsules is not suitable as a contraceptive.

Treatment should be discontinued upon diagnosis of a missed abortion.

Precautions:

Utrogestan Vaginal 200 mg Capsules contains soya lecithin and may cause hypersensitivity reactions (urticarial and anaphylactic shock in hypersensitive patients). As there is a possible relationship between allergy to soya and allergy to peanut, patients with peanut allergy should avoid using Utrogestan Vaginal 200mg Capsules.

Utrogestan Vaginal 200mg Capsules may interfere with the effects of bromocriptine and may raise the plasma concentration of ciclosporin. Utrogestan Vaginal 200mg Capsules may affect the results of laboratory tests of hepatic and/or endocrine functions.

Metabolism of Utrogestan Vaginal 200mg Capsules is accelerated by rifamycin medicines (such as rifampicin) and antibacterial agents.

The metabolism of progesterone by human liver microsomes was inhibited by ketoconazole (IC₅₀ <0.1 μM). Ketoconazole is a known inhibitor of cytochrome P450 3A4. These data therefore suggest that ketoconazole may increase the bioavailability of progesterone. The clinical relevance of the in vitro findings is unknown.

Pregnancy

No association has been found between the maternal use of natural progesterone in early pregnancy and foetal malformations.

Breastfeeding

Utrogestan Vaginal 200 mg Capsules is not indicated during breast-feeding.

Detectable amounts of progesterone enter the breast milk.

Fertility

As this medicinal product is indicated to support luteal deficiency in subfertile or infertile women, there is no deleterious known effect on fertility.

Utrogestan Vaginal Capsules has negligible influence on the ability to drive and use machines.

Post-Marketing experience

The information given below is based on extensive post marketing experience from vaginal administration of progesterone.

Adverse effects have been ranked under headings of frequency using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); frequency not known (cannot be estimated from the available data).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the website www.mhra.gov.uk/yellowcard.

Symptoms of overdosage may include somnolence, dizziness, euphoria or dysmenorrhoea. Treatment is observation and, if necessary, symptomatic and supportive measures should be provided.

Pharmacotherapeutic group: Sex hormones and modulators of the genital system, progestogens, ATC code: G03DA04.

Mechanism of action

Supplementation of the luteal phase during ART:

Progesterone is a natural progestogen, the main hormone of the corpus luteum and the placenta. It acts on the endometrium by converting the proliferating phase to the secretory phase. Utrogestan Vaginal 200mg Capsules have all the properties of endogenous progesterone with induction of a full secretory endometrium and in particular gestagenic, antiestrogenic, slightly anti-androgenic and antialdosterone effects.

Prevention of preterm birth

Progesterone is important during pregnancy in maintaining uterine quiescence by limiting the production of stimulatory prostaglandins responsible for uterine contractions. Progesterone also limits the release of matrix metalloproteinases that can cause cervical effacement and softening by inhibiting the expression of contraction-associated protein genes (ion channels, oxytocin and prostaglandin receptors, and gap junctions) within the myometrium.

Although levels of progesterone in the maternal circulation do not change significantly in the weeks preceding labour, the onset of labour at term and preterm is associated with a functional withdrawal of progesterone activity at the level of the uterus.

Absorption

Following oral administration, micronised progesterone is absorbed by the digestive tract. Pharmacokinetic studies conducted in healthy volunteers have shown that after oral administration of two 100 mg capsules (200mg), plasma progesterone levels increased to reach the Cmax of 13.8ng/ml +/- 2.9ng/ml in 2.2 +/- 1.4 hours. The elimination half-life observed was 16.8+/- 2.3 hours.

Although there were inter-individual variations, the individual pharmacokinetic characteristics were maintained over several months, indicating predictable responses to the drug.

Following vaginal administration, micronised progesterone is absorbed rapidly and achieves stable plasma levels in the range of 4-12 ng/ml, depending on the daily dose, with much less inter-subject variation than following oral administration.

Distribution

Progesterone is approximately 96%-99% bound to serum proteins, primarily to serum albumin (50%-54%) and transcortin (43%-48%).

Elimination

Urinary elimination is observed for 95% in the form of glycuroconjugated metabolites, mainly 3 α, 5 β–pregnanediol (pregnandiol).

Biotransformation

Progesterone is metabolised primarily by the liver.

Following oral administration, the main plasma metabolites are 20 α hydroxy- Δ 4 α- prenolone and 5 α-dihydroprogesterone. Some progesterone metabolites are excreted in the bile and these may be deconjugated and further metabolised in the gut via reduction, dehydroxylation and epimerisation. The main plasma and urinary metabolites are similar to those found during the physiological secretion of the corpus luteum.

Following vaginal administration, only low plasma levels of pregnanolone and 5α- dihydroprogesterone are detected, due to the lack of first-pass metabolism.

Preclinical data revealed no special hazard for humans based on conventional studies of safety pharmacology and toxicity.

Capsule contents:

Sunflower oil, refined

Soybean lecithin

Capsule shell:

Gelatin Glycerol

Titanium dioxide (E171)

Water, purified

Not applicable

3 years

This medicinal product does not require any special storage conditions.

The product is supplied in PVC/Aluminium blisters contained in cartons.

Pack sizes: Blister pack containing 15, 21, 45 or 90 capsules.

Not all pack sizes may be marketed

Any unused product or waste material should be disposed of in accordance with local requirements.

Besins Healthcare

Rue Washington 80

1050 Ixelles

Belgium

PL 28397/0005

21/12/2012

12/09/2017

30 August 2022