Clinical medicine profile
Progesterone
Progesterone [EPC]
- Route
- See product SmPC
- Schedule
- POM
- ATC
- Not assigned
- PPB status
- registered
Safety essentials
The information most likely to change a prescribing or dispensing decision.
WARNING: CARDIOVASCULAR DISORDERS, BREAST CANCER and PROBABLE DEMENTIA FOR ESTROGEN PLUS PROGESTIN THERAPY Cardiovascular Disorders and Probable Dementia Estrogens plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia. (See CLINICAL STUDIES and WARNINGS , Cardiovascular disorders and Probable dementia . ) The Women's Health Initiative (WHI) estrogen plus progestin substudy reported increased risks of deep vein thrombosis, pulmonary embolism, stroke and myocardial infarction in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg] combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo. (See CLINICAL STUDIES and WARNINGS , Cardiovascular disorders . ) The WHI Memory Study (WHIMS) estrogen plus progestin ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women. (See CLINICAL STUDIES and WARNINGS, Probable dementia and PRECAUTIONS, Geriatric Use . ) Breast Cancer The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer. (See CLINICAL STUDIES and WARNINGS, Malignant neoplasms, Breast Cancer. ) In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA, and other combinations and dosage forms of estrogens and progestins. Progestins with estrogens should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman. WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW ABOUT PROGESTERONE CAPSULES (A Progesterone Hormone)? Progesterone with estrogens should not be used to prevent heart disease, heart attacks, strokes, or dementia. Using progestins with estrogens may increase your chance of getting heart attacks, strokes, breast cancer, and blood clots. Using progestins with estrogens may increase your chance of getting dementia, based on a study of women age 65 and older. You and your healthcare provider should talk regularly about whether you still need treatment with progesterone capsules.
Contraindications
- CONTRAINDICATIONS Progesterone capsules should not be used in women with any of the following conditions: Progesterone capsules should not be used in patients with known hypersensitivity to its ingredients.
- Progesterone capsules contain peanut oil and should never be used by patients allergic to peanuts.
- Undiagnosed abnormal genital bleeding.
- Known, suspected, or history of breast cancer.
- Active deep vein thrombosis, pulmonary embolism or history of these conditions.
- Active arterial thromboembolic disease (for example, stroke and myocardial infarction), or a history of these conditions.
- Known liver dysfunction or disease.
- Known or suspected pregnancy.
Precautions
- WARNINGS See BOXED WARNING . 1.
- Cardiovascular disorders An increased risk of pulmonary embolism, deep vein thrombosis (DVT), stroke, and myocardial infarction has been reported with estrogen plus progestin therapy.
- Should any of these occur or be suspected, estrogen with progestin therapy should be discontinued immediately.
- Risk factors for arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (for example, personal history or family history of venous thromboembolism [VTE], obesity, and systemic lupus erythematosus) should be managed appropriately. a.
- Stroke In the Women’s Health Initiative (WHI) estrogen plus progestin substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women in the same age group receiving placebo (33 versus 25 per 10,000 women-years).
- The increase in risk was demonstrated after the first year and persisted.
- (See CLINICAL STUDIES .) Should a stroke occur or be suspected, estrogen plus progestin therapy should be discontinued immediately. b.
- Coronary Heart Disease In the WHI estrogen plus progestin substudy, there was a statistically non-significant increased risk of coronary heart disease (CHD) events (defined as nonfatal myocardial infarction [MI], silent MI, or CHD death) reported in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (41 versus 34 per 10,000 women-years).
- An increase in relative risk was demonstrated in year 1 and a trend toward decreasing relative risk was reported in years 2 through 5.
- (See CLINICAL STUDIES .) In postmenopausal women with documented heart disease (n = 2,763, average age 66.7 years), in a controlled clinical trial of secondary prevention of cardiovascular disease (Heart and Estrogen/Progestin Replacement Study [HERS]), treatment with daily CE (0.625 mg) plus MPA (2.5 mg) demonstrated no cardiovascular benefit.
- During an average follow-up of 4.1 years, treatment with CE plus MPA did not reduce the overall rate of CHD events in postmenopausal women with established coronary heart disease.
- There were more CHD events in the CE plus MPA-treated group than in the placebo group in year 1, but not during the subsequent years.
Dosing matrix
Population and organ-function guidance, shown together for faster comparison.
Oral progestogen component of HRT Adult: 200 mg OD at night for 12-14 days of each month. Oral Amenorrhoea Adult: 400 mg OD for 10 days. Oral _Dysfunctional uterine bleeding Adult: 400 mg OD for 10 days. IM Dysfunctional uterine bleeding Adult: 5-10 mg OD for 5-10 days until 2 days prior to expected onset of menstruation. IM Amenorrhoea Adult: 5-10 mg OD for 5-10 days until 2 days prior to expected onset of menstruation Recurrent miscarriage with progesterone deficiency Adult: 25-100 mg two times per week from the 15th day of pregnancy until 8-16 wk. Intrauterine Contraception Adult: Insert the device [38 mg of progesterone] into the uterine cavity Vaginal Dysfunctional uterine bleeding Adult: 45 mg every other day from the 15th-25th day of the cycle. May increase dose to 90 mg in non-responders Vaginal Amenorrhoea Adult: 45 mg every other day from the 15th-25th day of the cycle. May increase dose to 90 mg in non-responders Vaginal Premenstrual syndrome Adult: 200 mg daily [max. 400 mg BD]. Treatment is usually started on days 12-14 of the cycle and continues until onset of menstruation.
G. Pediatric Use Progesterone capsules are not indicated in children. Clinical studies have not been conducted in the pediatric population.
Review renal impairment dosing; many agents need CrCl/eGFR adjustment.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Review hepatic impairment dosing; monitor LFTs if agent is hepatically cleared or hepatotoxic.
Use, effects & interactions
Indications
- INDICATIONS AND USAGE Progesterone capsules are indicated for use in the prevention of endometrial hyperplasia in nonhysterectomized postmenopausal women who are receiving conjugated estrogens tablets.
- They are also indicated for use in secondary amenorrhea.
Adverse effects
- ADVERSE REACTIONS See BOXED WARNING , WARNINGS and PRECAUTIONS.
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- In a multicenter, randomized, double-blind, placebo-controlled clinical trial, the effects of progesterone capsules on the endometrium was studied in a total of 875 postmenopausal women.
- Table 6 lists adverse experiences greater than or equal to 2 percent of women who received cyclic progesterone capsules, 200 mg daily (12 days per calendar month cycle) with 0.625 mg conjugated estrogens or placebo.
- Table 6.
- Adverse Experiences (≥2%) Reported in an 875 Patient Placebo-Controlled Trial in Postmenopausal Women Over a 3-Year Period [Percentage (%) of Patients Reporting] Progesterone capsules 200 mg with Congugated Estrogens 0.625 mg Placebo (n=178) (n=174) Headache 31 27 Breast Tenderness 27 6 Joint Pain 20 29 Depression 19 12 Dizziness 15 9 Abdominal Bloating 12 5 Hot Flashes 11 35 Urinary Problems 11 9 Abdominal Pain 10 10 Vaginal Discharge 10 3 Nausea / Vomiting 8 7 Worry 8 4 Chest Pain 7 5 Diarrhea 7 4 Night Sweats 7 17 Breast Pain 6 2 Swelling of Hands and Feet 6 9 Vaginal Dryness 6 10 Constipation 3 2 Breast Carcinoma 2 <1 Breast Excisional Biopsy 2 <1 Cholecystectomy 2 <1 Effects on Secondary Amenorrhea In a multicenter, randomized, double-blind, placebo-controlled clinical trial, the effects of progesterone on secondary amenorrhea was studied in 49 estrogen-primed postmenopausal women.
- Table 7 lists adverse experiences greater than or equal to 5 percent of women who received progesterone or placebo.
- Table 7.
- Adverse Experiences (5%) Reported in Patients Using 400 mg/day in a Placebo-Controlled Trial in Estrogen-Primed Postmenopausal Women Adverse Experience Progesterone Capsules 400 mg Placebo n=25 n=24 Percentage (%) of Patients Fatigue 8 4 Headache 16 8 Dizziness 24 4 Abdominal Distention (Bloating) 8 8 Abdominal Pain (Cramping) 20 13 Diarrhea 8 4 Nausea 8 0 Back Pain 8 8 Musculoskeletal Pain 12 4 Irritability 8 4 Breast Pain 16 8 Infection Viral 12 0 Coughing 8 0 In a multicenter, parallel-group, open label postmarketing dosing study consisting of three consecutive 28-day treatment cycles, 220 premenopausal women with secondary amenorrhea were randomized to receive daily conjugated estrogens therapy (0.625 mg conjugated estrogens) and progesterone capsules, 300 mg per day (n=113) or Progesterone capsules, 400 mg per day (n=107) for 10 days of each treatment cycle.
- Overall, the most frequently reported treatment-emergent adverse reactions, reported in greater than or equal to 5 percent of subjects, were nausea, fatigue, vaginal mycosis, nasopharyngitis, upper respiratory tract infection, headache, dizziness, breast tenderness, abdominal distension, acne, dysmenorrhea, mood swing, and urinary tract infection.
- Postmarketing Experience: The following additional adverse reactions have been reported with progesterone capsules.
- Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.
- Genitourinary System: endometrial carcinoma, hypospadia, intra-uterine death, menorrhagia, menstrual disorder, metrorrhagia, ovarian cyst, spontaneous abortion.
- Cardiovascular: circulatory collapse, congenital heart disease (including ventricular septal defect and patent ductus arteriosus), hypertension, hypotension, tachycardia.
Drug interactions
Open multi-drug checker ↗- Professional use: confirm indication, dose, duration, monitoring and patient counselling points against current Kenya STG / EML and the product SmPC.
- Document allergy status and key interactions.
Mechanism & disposition
Mechanism is agent-specific.
Read complete mechanism
Mechanism is agent-specific. At receptor, enzyme, ion channel, transporter or microbial target level, the drug alters a physiological or pathological pathway to produce its therapeutic effect. Confirm precise molecular mechanism in current SmPC / pharmacology reference for this INN before high-stakes decisions.
Product-specific
Product-specific
See product SmPC
After oral administration of progesterone as a micronized soft-gelatin capsule formulation, maximum serum concentrations were attained within 3 hours. The absolute bioavailability of micronized progesterone is not known. Table 1 summarizes the mean pharmacokinetic parameters in p...
Progesterone is approximately 96 percent to 99 percent bound to serum proteins, primarily to serum albumin (50 to 54 percent) and transcortin (43 to 48 percent). C.
Progesterone is metabolized primarily by the liver largely to pregnanediols and pregnanolones. Pregnanediols and pregnanolones are conjugated in the liver to glucuronide and sulfate metabolites. Progesterone metabolites which are excreted in the bile may be deconjugated and may b...
The glucuronide and sulfate conjugates of pregnanediol and pregnanolone are excreted in the bile and urine. Progesterone metabolites are eliminated mainly by the kidneys. Progesterone metabolites which are excreted in the bile may undergo enterohepatic recycling or may be excrete...
of the conjugated estrogens was similar with coadministration of progesterone capsules. Table 2 summarizes the pharmacokinetic parameters. TABLE 2. Mean (± S.D.) Pharmacokinetic Parameters for Estradiol, Estrone, and Equilin Following coadministration of Conjugated Estrogens 0.62...
Pregnancy, lactation & diet
E. Pregnancy Progesterone capsules should not be used during pregnancy. (See CONTRAINDICATIONS .) Pregnancy Category B: Reproductive studies have been performed in mice at doses up to 9 times the human oral dose, in rats at doses up to 44 times the human oral dose, in rabbits at a dose of 10 mcg/day delivered locally within the uterus by an implanted device, in guinea pigs at doses of approximately one-half the human oral dose and in rhesus monkeys at doses approximately the human dose, all based on body surface area, and have revealed little or no evidence of impaired fertility or harm to the fetus due to progesterone.
F. Nursing Women Detectable amounts of progestin have been identified in the milk of nursing women receiving progestins. Caution should be exercised when progesterone capsules are administered to a nursing woman.
Brands & loaded prices
| Brand | Manufacturer | Pack | Observed price |
|---|---|---|---|
| GESTAGLEN 400 | Glenmark Pharmaceuticals Ltd | Capsule, Soft | Unavailable |
| SUSTEN | DAIMA BIASHARA / Wholesale Import | 200MG * 30`S | KES 2,257.50Daima Chemist price-list reference ↗ Source date not recorded · verify current price |
Sources & review state
Decision support only. Confirm patient-specific decisions against the current product SmPC, Kenya STG/EML, and professional judgement.