Adult: Due to hormonal imbalance in the absence of organic pathologies, such as uterine cancer or submucous fibroids: 5-10 mg once daily for 6 doses. When estrogen is given as well, the administration begins after 2 weeks of estrogen therapy. Discontinue if menstrual flow begins during injections of progesterone. Dosage recommendations may vary among countries or individual products. Refer to specific product guidelines.
Intramuscular Amenorrhoea
Adult: 5-10 mg once daily for 6-8 consecutive days.
Adult: In patients who require progesterone supplementation for luteal support who are unable to use or tolerate vaginal preparations: 25 mg once daily from the day of oocyte retrieval up to week 12 of pregnancy, given via SC or IM inj.
Oral Menopausal hormone replacement therapy
Adult: As an adjunct to estrogen in post-menopausal women with an intact uterus: 200 mg once daily at bedtime for 12 days in the last half of each therapeutic cycle (beginning on day 15 of the cycle and ending on day 26). Alternatively, 100 mg once daily at bedtime from day 1-25 of each therapeutic cycle.
Oral Prophylaxis of endometrial hyperplasia
Adult: In non-hysterectomised postmenopausal women who are receiving conjugated estrogen: 200 mg once daily at bedtime for 12 days sequentially per 28-day cycle.
Adult: In patients who use barrier methods of contraception or those who suffer from vaginal infection (especially moniliasis) or recurrent cystitis or have recently given birth: As pessary: 200-400 mg bid. For premenstrual syndrome, start treatment on days 12-14 of the menstrual cycle and continue treatment until the onset of menstruation.
Vaginal Assisted reproductive technology
Adult: As gel: In patients who require progesterone supplementation: 90 mg (8%) once daily. In women with partial or complete ovarian failure who require progesterone replacement: 90 mg (8%) bid. If pregnancy occurs, treatment may be continued up to 10-12 weeks. In patients who require progesterone supplementation for luteal support: As insert: 100 mg bid-tid starting the day after the oocyte retrieval and continuing for up to 10 weeks total duration. As pessary: 400 mg bid starting at oocyte retrieval. Continue for 38 days if pregnancy has been confirmed. As cap: 200 mg tid to be inserted deep into the vagina from the day of embryo transfer until at least the 7th week of pregnancy and not later than the 12th week of pregnancy. As vaginal tab: 100 mg tid starting at oocyte retrieval. Continue for 30 days if pregnancy has been confirmed. Dosage recommendations may vary among countries or individual products. Refer to specific product guidelines.
Vaginal Secondary amenorrhoea
Adult: As gel: 45 mg (4%) every other day up to a total of 6 doses. May increase to 90 mg (8%) every other day up to a total of 6 doses if the response is inadequate.
Adult: In patients who suffer from colitis or faecal incontinence: As pessary: 200-400 mg bid. For premenstrual syndrome start treatment on days 12-14 of the menstrual cycle and continue treatment until the onset of menstruation.
Administration
Should be taken on an empty stomach.
Contraindications
Hypersensitivity to progesterone, soybean lecithin, peanut, palm oil, or sesame seed/oil. Undiagnosed vaginal bleeding, known or suspected malignancy of the breast or genital organs, missed abortion or ectopic pregnancy, active or history of thrombophlebitis or thromboembolic disorders, porphyria. Severe hepatic impairment. Pregnancy (oral cap).
Special Precautions
Patient with diseases that may be exacerbated by fluid retention (e.g. cardiac impairment, asthma, migraine, epilepsy), diabetes, hypercholesterolaemia, hypertension, SLE, personal or family history of venous thromboembolism, history of depression. Patients undergoing surgery; obese, smokers, >35 years. Abrupt withdrawal. Renal and mild to moderate hepatic impairment. Pregnancy and lactation.
Adverse Reactions
Significant: Increased risk of invasive breast cancer, endometriosis, transient dizziness and drowsiness, eosinophilic pneumonia (particularly in inj preparations containing sesame oil), fluid retention, retinal vascular thrombosis, increase risk of probable dementia (in women ≥65 years), toxic shock syndrome (vaginal preparations); increase risk of DVT, pulmonary embolism, stroke, MI; decrease glucose tolerance. Rarely, increase the risk of ovarian cancer. Cardiac disorders: Chest pain (oral). Gastrointestinal disorders: Abdominal pain, bloating, nausea, vomiting, diarrhoea, constipation, cramps, abdominal distention. General disorders and admin site conditions: Irritability, fatigue, pyrexia; injection site pain, irritation, swelling, redness, haematoma, or induration. Hepatobiliary disorders: Cholestatic jaundice. Infections and infestations: Viral infection; UTI (vaginal insert). Metabolism and nutrition disorders: Weight changes, peripheral oedema. Musculoskeletal and connective tissue disorders: Musculoskeletal pain. Nervous system disorders: Headache, nervousness. Psychiatric disorders: Depression, anxiety, insomnia. Renal and urinary disorders: Urinary problems. Reproductive system and breast disorders: Breast tenderness, breast hypertrophy, mastalgia, vaginal discharge, decreased libido, irregular menstruation, amenorrhea; perineal pain, dyspareunia, genital candidiasis (vaginal gel); uterine spasm (vaginal insert/tab); vaginal haemorrhage, vulvovaginal dryness, vaginal burning sensation, vulvovaginal discomfort (vaginal insert/cap); breakthrough bleeding, spotting, change in menstrual flow, galactorrhoea not associated with childbirth (inj). Respiratory, thoracic and mediastinal disorders: Cough (oral). Skin and subcutaneous tissue disorders: Rash, urticaria, melasma, alopecia; genital pruritus (vaginal gel/vaginal tab/inj); acne vulgaris, hirsutism (inj). Vascular disorders: Hot flush.
This drug may cause drowsiness and/or dizziness, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor blood pressure; serum triglycerides (2 weeks after starting therapy in patients with baseline level >200 mg/dL) and TSH (6-12 months after starting oral therapy in patients taking thyroid replacement) during therapy. Perform age-appropriate breast and pelvic exams during therapy. Assess baseline risk for breast cancer and CV disease prior to combination hormonal therapy for menopause women. Monitor unscheduled bleeding lasting >6 months for endometrial pathology (sooner in patients with a history of endometrial cancer; obese or diabetic). Assess efficacy beginning 1-3 months after starting therapy, then every 6-12 months as needed. Evaluate the duration of treatment at least annually.
Decreased bioavailability with CYP3A4 inducers (e.g. rifampicin, carbamazepine, phenobarbital, phenytoin, griseofulvin, spironolactone). Increased bioavailability with CYP3A4 inhibitors (e.g. ketoconazole, ritonavir). May inhibit ciclosporin metabolism leading to increase plasma ciclosporin concentrations and risk of toxicity. May diminish the therapeutic effect of antidiabetic agents. May diminish the therapeutic effect with other vaginal products (e.g. antifungal agents).
Food Interaction
Decreased bioavailability with St. John’s wort. Increased bioavailability with food (oral cap).
Lab Interference
Altered metyrapone test; increased sulfobromophthalein retention and other hepatic function tests; increase in prothrombin factors VII, VIII, IX, and X in coagulation tests; altered pregnanediol determinations; increase in PBI and butanol extractable protein-bound iodine and decrease in T3 uptake values in thyroid function tests.
Action
Description: Mechanism of Action: Progesterone, a naturally occurring steroid that is secreted by the ovary, placenta, and adrenal gland that acts on the endometrium by converting the proliferative phase to the secretory phase. It promotes mammary gland development, blocks follicular maturation and ovulation, relaxes uterine smooth muscle, maintains pregnancy, and induces adequate endometrial maturity, thus promoting embryo implantation. Pharmacokinetics: Absorption: Prolonged (vaginal gel). Time to peak plasma concentration: Within 3 hours (oral); approx 8 hours (inj); 3.55 ± 2.48 to 7 ± 2.88 hours (vaginal gel); 17.3-24 hours (vaginal insert); 1-3 hours (vaginal cap). Distribution: Enters breast milk. Plasma protein binding: Approx 96-99%, mainly to albumin (50-54%) and cortisol-binding globulin (43-48%). Metabolism: Metabolised in the liver to pregnanediols and pregnanolones which are then conjugated to glucuronide and sulfate metabolites. Metabolites that are excreted in the bile may be deconjugated and may be further metabolised in the gut via reduction, dehydroxylation and epimerisation. Excretion: Mainly via urine (50-60% as metabolites); bile and faeces (approx 10%).
Chemical Structure
Progesterone Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 5994, Progesterone. https://pubchem.ncbi.nlm.nih.gov/compound/Progesterone. Accessed Nov. 25, 2021.
Storage
Store at 20-25°C. Storage recommendations may vary among countries or individual products. Refer to specific product guidelines.
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