GynProgesterone

Ovoid soft capsules, off-white colored, containing a thick whitish suspension.
GynProgesterone 100 mg: Each soft capsule contains 100 mg of micronised progesterone (INN).
GynProgesterone 200 mg: Each soft capsule contains 200 mg of micronised progesterone (INN).
Excipients with known effect: GynProgesterone 100 mg contains 149 mg of peanut oil per soft capsule.
GynProgesterone 200 mg contains 298 mg of peanut oil per soft capsule.
Excipients/Inactive Ingredients: Peanut oil and Soy lecithin.
Capsule shell: Gelatin, Glycerol, Titanium dioxide.

Pharmacotherapeutic group: Urogenital system and sex hormones. ATC: G03DA04.
Pharmacology: Pharmacodynamics: Mechanism of action: Progesterone is a progestinic hormone secreted mainly from the corpus luteum of the ovary during the latter half of the menstrual cycle. Progesterone is formed from steroid precursors in the ovary, testis, adrenal cortex, and placenta. Luteinizing hormone (LH) stimulates the synthesis and secretion of progesterone from the corpus luteum. Progesterone is necessary for nidation (implantation) of the ovum and for maintenance of pregnancy.
Progesterone shares the pharmacologic actions of the progestins. Progesterone stimulates the growth of mammary alveolar tissue and relaxes uterine smooth muscle. Progesterone has minimal estrogenic and androgenic activity.
Pharmacokinetics: Progesterone has a short elimination half-life and undergoes extensive first-pass hepatic metabolism when given orally; oral bioavailability is very low although it may be increased somewhat by an oily vehicle and by micronisation. Progesterone is absorbed when given buccally, rectally, or vaginally, and rapidly absorbed from the site of an oily intramuscular injection.
Various derivatives have been produced to extend the duration of action and to improve oral activity. Esters of progesterone derivatives such as hydroxyprogesterone caproate are used intramuscularly, and megestrol acetate is orally active. The ester medroxyprogesterone acetate is used orally and parenterally. 19-Nortestosterone progestogens have good oral activity because the 17-ethinyl substituent slows hepatic metabolism.
Progesterone and the progestogens are highly protein bound; progesterone is bound to albumin and corticosteroid binding globulin; esters such as medroxyprogesterone acetate are mainly bound to albumin; and 19-nortertosterone analogues are bound to sex-steroid binding globulin and albumin. Progesterone is metabolized in the liver to various metabolites including pregnanediol, which are excreted in the urine as sulfate and glucuronide conjugates. Similarly, progestogens undergo hepatic metabolism to various conjugates, which are excreted in the urine. Progesterone is distributed into breast milk.
Toxicology: Preclinical safety data: The carcinogenic and mutagenic potentials of progesterone have not been specifically determined.

Oral administration: Disorders related to progesterone insufficiency and in particular: Primary and secondary amenorrhea; Premenstrual disorder; Bleeding due to fibroma; Adjunctive use with oestrogen in post-menopausal women.
Vaginal administration: To help pregnancy, in particular: Luteal phase support during in vitro fertilisation (IVF) cycles; Threatened miscarriage or prevention of habitual miscarriage due to luteal phase deficiency up to the 12^th week of pregnancy; Preterm labour.

Oral administration: In progesterone insufficiency the average dosage is from 200 to 300 mg micronised progesterone per day.
In pre-menstrual disorders, amenorrhea (primary & secondary) and bleeding due to fibroma, the usual treatment regimen is 200 to 300 mg per day: 200 mg in a single evening dose before going to bed, or 300 mg in 2 divided doses (200 mg before going to bed and 100 mg in the morning if necessary), 10 days per cycle, usually from the 17^th to the 26^th day inclusive.
In hormone replacement therapy in women receiving isolated estrogen there is an increased risk of endometrial cancer which should be countered by progesterone administration.
100 mg single dose can be given at bedtime from day 1 to day 25 of each therapeutic cycle, withdrawal bleeding being less with this treatment schedule.
200 mg single dose or 100 mg two doses during in the evening to bedtime, 12 to 14 days per month, or the last two weeks of each treatment sequence. This treatment must be followed by the total discontinuation of any replacement therapy for approximately one week during which a deprivation haemorrhage is often observed.
Vaginal administration: Supplementation of the luteal phase during IVF cycles: The recommended dosage is from 400 to 600 mg per day, in two to three divided doses, from the day of hCG injection up until the 12^th week of pregnancy.
Threatened miscarriage or prevention of habitual miscarriage due to luteal phase insufficiency: the recommended dosage is from 200 to 400 mg per day in two divided doses up until the 12^th week of pregnancy.
Preterm labour: Women with a history of preterm labour - 100 mg per day, given from 20 weeks of gestation until the risk of prematurity is low. Women with cervix shorter than 15 mm detected at 22-26 weeks - 200 mg per day until 36^th week of pregnancy.
Method of administration: Oral: take the capsules with a glass of water at the same time each day apart from mealtimes.
Vaginal: insert the capsules deep into the vagina by pushing them with a finger.

No case of overdosage was reported with progesterone. In the case of overdosage, progesterone capsules should be discontinued, and the patient should be treated symptomatically.

History of hypersensitivity to the active substances or to any of the excipients listed in Description.
This medicinal product contains peanut oil. It must not be used if the patient is allergic to peanuts or soy.
Undiagnosed vaginal bleeding.
Mammary or genital tract carcinoma.
Oral administration: abnormal liver function.
Thrombophlebitis.
History of thromboembolic disorders.
Cerebral haemorrhage.
Porphyria.

The treatment is not contraceptive, taken according to the recommended dosage and conditions of use.
Prior to taking hormone (and at regular intervals thereafter) each woman should be assessed.
A personal and family medical history should be taken and physical examination should include special reference to breast and pelvic organ as well as cervical cytology. Progesterone capsules should be used cautiously in patients such as with conditions that might be aggravated by fluid retention (e.g. cardiac disease, renal disease, epilepsy, migraine, asthma): in patients with a history of depression, diabetes, mild to moderate hepatic dysfunction, migraine.
Effects on the ability to drive and use machines: The risk of drowsiness and/or dizziness has been reported in relation to oral use of the medicinal product. People who have to drive and use machines should therefore be warned that this is possible.
Use in Pregnancy: During pregnancy, progesterone should only be used vaginally and restricted to the first trimester; there is a risk of undesirable effects on the liver during the second and third trimesters.

Pregnancy: Progesterone is used to support embryo implantation and maintain pregnancy as a component of assisted reproductive technology (ART) treatment in infertile women. Such use is associated with increased ongoing pregnancy rates.
There have also been reports of congenital malformations, including limb reduction defects, neural tube defects, and congenital heart malformations, after intra-uterine exposure to progestogen in early pregnancy. However, many analyses of accumulated data have found no evidence of a recognisable malformation syndrome.
Lactation: Progesterone is excreted in breast milk. Administration is not therefore recommended in women who are breastfeeding.

Dizziness, headache, abdominal pain, fatigue, viral infection, abdominal distention, musculoskeletal pain, emotional lability, irritability, and upper respiratory tract infection. Extreme dizziness and/or drowsiness, blurred vision, slurred speech, difficulty walking, loss of consciousness, vertigo, confusion, disorientation, and shortness of breath have been reported in a few women receiving the drug. Hypotension and syncope have occurred rarely in women receiving progesterone capsules. Menstrual disturbances, premenstrual-like syndrome (including bloating, fluid retention, breast tenderness), weight change, nausea, insomnia, depression, change in libido; also, skin reactions (including urticaria, pruritus, rash and acne), hirsutism and alopecia. Jaundice and anaphylactoid reactions have also been reported.

Food: Concomitant food ingestion increased the bioavailability of Micronised Progesterone Capsules.
Drug: Enzyme-inducing drugs such as carbamazepine, griseofulvin, phenobarbital, phenytoin, and rifampicin may enhance the clearance of progesterone and the progestogens.
The metabolism of progesterone by human liver microsomes was inhibited by ketoconazole (IC₅₀ <0.1 μM). Ketoconazole and other inhibitors of CYP450-3A4 such as ritonavir and nelfinavir may increase bioavailability of progesterone.
Laboratory tests: Progesterone may affect the results of laboratory tests of hepatic and/or endocrine functions.

Incompatibilities: Not applicable.

Store below 30°C.
Shelf-life: 3 years.

Oestrogens, Progesterones & Related Synthetic Drugs

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

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