Exprogest

Progesterone (Exprogest) 200 mg Vaginal: Each soft gel capsule contains 200 mg of progesterone.
Excipients with known effect: Progesterone (Exprogest) 200 mg Vaginal contains soya bean lecithin.

Pharmacotherapeutic group: Sex hormones and modulators of the genital system, progestogens. ATC code: G03DA04.
Pharmacology: Pharmacodynamics: Progesterone (Exprogest), which contains micronised progesterone, significantly raises plasma progesterone concentrations after oral use. It therefore corrects progesterone deficiencies.
The active ingredient, progesterone, is chemically identical to the progesterone produced by the corpus luteum during the female ovarian cycle. It exerts many biological actions, mainly on target tissues previously sensitized by estrogens. Progesterone transforms proliferative endometrium into secretory state.
In postmenopausal women, estrogens promote the growth of the endometrium and unopposed oestrogens increase the risk of endometrial hyperplasia and cancer. The addition of a progesterone greatly reduces the estrogen induced risk of endometrial hyperplasia in non-hysterectomised women.
During pregnancy, progesterone increases endometrial receptivity for implantation of an embryo. Once the embryo has been implanted, progesterone acts to maintain the pregnancy. Progesterone also relaxes uterine smooth muscle.
Pharmacokinetics: Absorption: Absorption through the vaginal mucosa is rapid, producing high plasma concentrations of progesterone after 1 hour.
Distribution: Peak plasma concentration is reached 2-6 hours after application. After administration of 100 mg in the morning and 100 mg at night, a mean plasma concentration of 9.7 ng/ml (30.9 nmol/l) is obtained for 24 hours. This dosage of 200 mg per day induces stable physiological plasma concentrations of progesterone, similar to those observed during the luteal phase of a menstrual cycle with normal ovulation. Inter-individual variations of progesteronaemia are less with vaginal administration and results can therefore be better predicted using this route. With doses of over 200 mg per day, progesterone plasma concentrations comparable to those described during the first trimester of pregnancy are obtained.
Metabolism: The plasma concentration of 5β-pregnenolone does not increase with this route of administration.
Elimination: Urinary elimination is primarily in the form of 5α,5β-pregnanediol (pregnandiol), as shown by the rise in its concentration (which reaches its peak level of 142 ng/ml (415.6 nmol/l) at 6 hours).
Toxicology: Preclinical safety data: Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction.

Progesterone (Exprogest) is indicated for adults.
Vaginal use: Replacement in progesterone during the course of complete deficits in women with non-functioning ovaries (ovum transplant); Supplementation of the luteal phase during the course of cycles of in vitro fertilization (IVF); Supplementation of the luteal phase during the course of spontaneous or induced cycles in case of hypofertility or primary or secondary sterility due to dysovulation; Threat of abortion or prevention of repetitive abortions due to luteal insufficiency.

Dosage: The recommended dose is as follows, according to the indication: Replacement of progesterone during the course of complete deficits in women with non-functioning ovaries (ovum transplant): As a complement of an appropriate estrogenic treatment: 100 mg of progesterone/day on the 13th and 14th day of the transfer cycle. Then 200 mg/day (100 mg of progesterone in the morning + 100 mg of progesterone at night) from the 15th day to the 25th day of the cycle. From day 26 and in case of pregnancy, the dose is increased by 100 mg progesterone/day every week, to reach the maximum dose of 600 mg of progesterone per day divided into three doses. This dosage will be maintained until the 60th day.
Supplementation of the luteal phase during the course of in vitro fertilization cycles (IVF): The recommended dosage is 400 to 600 mg of progesterone/day, from the day that HCG is injected until the 12th week of pregnancy.
Supplementation of the luteal phase during the course of spontaneous or induced cycles, in cases of hypofertility or primary or secondary sterility due to dysovulation: The recommended dosage is 200 to 300 mg of progesterone per day from the 17th day of the cycle, for 10 days and resume as soon as possible in case of absence of periods and diagnosis of pregnancy.
Threat of abortion or prevention of repetitive abortions due to luteal insufficiency: The recommended dosage is 200 to 400 mg of progesterone/day in two doses.
Paediatric population: There is no relevant use of Progesterone (Exprogest) in the paediatric population.
Method of administration: Insert the capsules into the vagina deeply by pushing them with the finger.

The adverse reactions described in Adverse Reactions are usually signs of overdose. These disappear without treatment when the dosage is reduced.
The usual dosage may be excessive in some people because of persistence or recurrence of unstable endogenous progesterone secretion, particular sensitivity to the substance or excessively low concomitant blood oestradiol concentrations. In these situations: The dosage should be reduced or the progesterone should be administered AT BEDTIME IN THE EVENING, 10 days per cycle, if drowsiness or fleeting dizziness occurs.
Treatment should be started later in the cycle (such as on day 19 instead of day 17) if the cycle is shortened or spotting occurs.
Check that oestradiol concentrations are sufficient in the perimenopausal period and in hormone replacement therapy for the menopause.

This medicinal product must not be used in the following situations: Hypersensitivity to the active substances or to any of the excipients listed in Description.
Undiagnosed genital bleeding.
Severe liver dysfunction.
Liver tumors.
Suspected or confirmed breast or genital organ neoplasia.
Thromboembolic diseases, active or in the history.
Cerebral haemorrhage.
Porphyria.
In case of a contraindication related with estrogens when Progesterone (Exprogest) is used for HRT in conjunction with an estrogen (see summaries of product characteristics of the particular estrogen-containing medicinal product).
Progesterone (Exprogest) contains soya bean lecithin. If the patient is allergic to peanut or soya, do not use this medicinal product.

Under the recommended conditions for use, this treatment is NOT A CONTRACEPTIVE.
The risks of combined use of estrogen and progestogen for postmenopausal hormone therapy are described in detail in the summaries of product characteristics of the particular estrogen-containing medicinal products.
Patients must be monitored closely if they have a past history of venous thrombosis.
If uterine bleeding is present, do not prescribe before establishing a cause, particularly with endometrial investigations.
Because of the metabolic risks and risks of thromboembolism which cannot be entirely excluded, administration should be discontinued in the event of: Ocular disorders such as reduced vision, diplopia and retinal vascular lesions; Venous thromboembolic or thrombotic events, regardless of location; Severe headaches.
If the patient develops amenorrhoea during treatment, ensure that she is not pregnant. The use of progesterone in cases of threatened abortion or prevention of repetitive abortion should be reserved for cases in which the secretion of the corpus luteum is insufficient. More than half of early miscarriages are due to genetic disorders. Other infectious or mechanical processes may be the cause of the abortion. In these cases the administration of progesterone would only have the effect of delaying the expulsion of a dead embryo or delaying the interruption of a nonevolutive pregnancy.
The use of Progesterone (Exprogest) in the course of pregnancy should be reserved for the first trimester and should only be used vaginally. There are risks of undesirable effects on the liver during the 2nd and 3rd trimesters of pregnancy.
Medical examination/follow-up: Before initiating or reinstituting HRT, a complete personal and family medical history should be taken. Physical (including pelvic and breast) examination should be guided by this and by the contraindications and warnings for use. During treatment, periodic check-ups are recommended of a frequency and nature adapted to the individual woman. Women should be advised what changes in their breasts should be reported to their doctor or nurse. Investigations, including appropriate imaging tools, e.g. mammography, should be carried out in accordance with currently accepted screening practices, modified to the clinical needs of the individual.
Endometrial hyperplasia: In women with intact uterus, regular period-like bleeding is likely to occur upon withdrawal during the treatment with estrogen and Progesterone (Exprogest). Such bleeding may decrease or stop altogether with increasing atrophy of the endometrium in the course of long-term treatment. In the absence of withdrawal bleeding, endometrial hyperplasia should be excluded by suitable measures.
Breakthrough bleeding and spotting may occur during the first few months of treatment. If such breakthrough bleeding or spotting occurs later in the course or the therapy, or continues after treatment has been discontinued, the reason should be investigated, which may include endometrial biopsy to exclude endometrial malignancy.
Long-term treatment (>5 years) with combinations of estrogen and progesterone, such as Progesterone (Exprogest), may offer less endometrial protection than combinations of estrogen and progestogen. Therefore, regular endometrial monitoring is recommended.
Progesterone (Exprogest) contains soya bean lecithin: Progesterone (Exprogest) contains soya bean lecithin and may cause hypersensitivity reactions (urticaria and anaphylactic shock). If a patient is allergic to peanut or soya, the patient should not use this medicinal product (see Contraindications).

Pregnancy: A large amount of data on pregnant women indicates no malformative nor feto/neonatal toxicity of vaginal progesterone.
Breast-feeding: There is insufficient information on the excretion of progesterone/metabolites in human milk. Secretion of progesterone into breast milk has not been studied in detail. Progesterone (Exprogest) should not be used during breastfeeding.
Fertility: As this medicinal product is indicated to support luteal failure in subfertile or infertile women, there is not deleterious known effect on fertility.

No general secondary effects, such as drowsiness or fleeting dizzy sensations appear at the recommended dose.
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.

Drugs known to induce the hepatic CYP450-3A4 such as barbiturates, anti-epileptic agents (phenytoin, carbamazepine), rifampicin, phenylbutazone, spironolactone, griseofulvin, some antibiotics (ampicillins, tetracyclines) and also herbal products containing St. John's wort [Hypericum perforatum] may increase metabolism and the elimination of progesterone.
Ketoconazole and other inhibitors of CYP450-3A4 may increase bioavailability of progesterone. Progesterone may affect the results of laboratory tests of hepatic and/or endocrine functions.
Progestogens may decrease glucose tolerance and thus, may increase insulin resistance or resistance to any other antidiabetic agents used in patients with diabetes mellitus.

Incompatibilities: None known.
Special Precautions for Disposal: Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Store at temperatures not exceeding 30 °C.

Oestrogens, Progesterones & Related Synthetic Drugs

G03DA04 - progesterone ; Belongs to the class of pregnen (4) derivative progestogens.

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