MICROGESTIN 1.5/30
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MICROGESTIN 1.5/30 (MICROGESTIN 1.5/30).
Combination oral contraceptive containing norethindrone acetate (progestin) and ethinyl estradiol (estrogen). Suppresses gonadotropin secretion (FSH, LH) via negative feedback on hypothalamic-pituitary axis, preventing ovulation. Also increases cervical mucus viscosity and alters endometrial receptivity.
| Metabolism | Norethindrone acetate is deacetylated to norethindrone, primarily metabolized via cytochrome P450 3A4 (CYP3A4) to reduced metabolites, sulfates, and glucuronides. Ethinyl estradiol is metabolized primarily by CYP3A4, undergoes hydroxylation, and undergoes conjugation (glucuronidation and sulfation). Both undergo enterohepatic recirculation. |
| Excretion | Renal: ~50-60% (primarily as glucuronide conjugates of ethinyl estradiol and norethindrone); Fecal: ~40-50% (via biliary elimination) |
| Half-life | Norethindrone: 8-11 hours; Ethinyl estradiol: 13-19 hours. Steady-state reached within 5-7 days. |
| Protein binding | Norethindrone: 90-95% bound to SHBG and albumin; Ethinyl estradiol: 95-98% bound to albumin, with 2-5% free. |
| Volume of Distribution | Norethindrone: 3-5 L/kg; Ethinyl estradiol: 2-4 L/kg. High Vd indicates extensive tissue distribution. |
| Bioavailability | Oral: Norethindrone ~64-75%; Ethinyl estradiol ~45-60% due to first-pass metabolism. |
| Onset of Action | Oral: Contraceptive effect achieved within 7 days of consistent daily dosing; peak hormone levels at 1-4 hours post-dose. |
| Duration of Action | 24 hours (daily dosing required). Clinical effect persists for the entire dosing interval if taken consistently. |
One tablet (norethindrone acetate 1.5 mg/ethinyl estradiol 30 mcg) orally once daily at the same time each day for 21 consecutive days, followed by 7 days of placebo tablets.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment is required for patients with renal impairment. However, because of potential fluid retention, use with caution in patients with renal dysfunction. |
| Liver impairment | Contraindicated in patients with acute liver disease or hepatocellular carcinoma. For Child-Pugh class A: use with caution; class B or C: not recommended due to potential for impaired hormone metabolism. |
| Pediatric use | Safety and effectiveness in pediatric patients under 18 years have not been established. Not indicated for use before menarche. |
| Geriatric use | Not indicated for use in postmenopausal women. No specific dosing recommendations in elderly; evaluate risk-benefit considering comorbidities (e.g., cardiovascular disease). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MICROGESTIN 1.5/30 (MICROGESTIN 1.5/30).
| Breastfeeding | Small amounts of oral contraceptive steroids (including norethindrone and ethinyl estradiol) are excreted in breast milk. The M/P ratio is approximately 0.5 for norethindrone and 0.01–0.02 for ethinyl estradiol. Use during lactation may decrease milk production and quality. Not recommended for use in nursing mothers until weaning is complete. Alternative methods of contraception should be considered. |
| Teratogenic Risk | First trimester: An increased risk of cardiovascular defects and oral clefts following first-trimester exposure to oral contraceptives has been suggested but not confirmed. Norethindrone and ethinyl estradiol are not recommended during pregnancy. If pregnancy occurs, the drug should be discontinued. Second and third trimesters: Exposure to estrogens and progestins may cause fetal harm, including urogenital abnormalities in female fetuses (e.g., hypospadias in males, clitoral enlargement, labial fusion in females). Use is contraindicated during known or suspected pregnancy. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events (thrombophlebitis, venous thromboembolism, stroke, myocardial infarction) from combination oral contraceptive use. Risk increases with age and heavy smoking (≥15 cigarettes/day). Women over 35 who smoke should not use this product.
| Serious Effects |
Active or history of thrombophlebitis or thromboembolic disorders. Cerebrovascular or coronary artery disease. Known or suspected pregnancy. Undiagnosed abnormal uterine bleeding. Known or suspected breast carcinoma or other estrogen-/progestin-sensitive neoplasia. Hepatic adenoma or carcinoma. Jaundice or cholestatic jaundice of pregnancy, or history of jaundice with prior oral contraceptive use. Acute or chronic hepatocellular disease with abnormal liver function. Heavy smoking (≥15 cigarettes/day) in women >35 years. Hypersensitivity to any component.
| Precautions | Increased risk of thromboembolic disorders (venous thromboembolism, arterial thrombosis), stroke, myocardial infarction, especially in smokers >35 years. Hepatic neoplasia (benign and malignant), hypertension, gallbladder disease, carbohydrate/lipid effects, headache/migraine exacerbation, visual disturbances (retinal thrombosis). Breakthrough bleeding/spotting. Hepatic enzyme induction (e.g., rifampin) may reduce contraceptive efficacy. |
Loading safety data…
| Fetal Monitoring | Monitor blood pressure regularly, especially if there is a history of hypertension. Perform pelvic exams annually, including Pap smear. Monitor for signs of thromboembolic events, depression, and glucose intolerance. In case of pregnancy, ultrasound for fetal development and anomaly screening. |
| Fertility Effects | Suppresses ovulation via inhibition of gonadotropin release. After discontinuation, return to fertility may be delayed but is not permanently impaired. Some women may experience anovulatory cycles temporarily post-discontinuation. |