MODICON 28
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MODICON 28 (MODICON 28).
Combination hormonal contraceptive: ethinyl estradiol suppresses gonadotropin release, inhibiting ovulation; norethindrone induces changes in cervical mucus and endometrium, impeding sperm penetration and implantation.
| Metabolism | Ethinyl estradiol undergoes hepatic metabolism via CYP3A4; norethindrone is metabolized primarily via reduction and conjugation, with involvement of CYP3A4. |
| Excretion | Renal: 50-60% as metabolites, fecal: 40-50% as metabolites, with enterohepatic circulation; less than 1% unchanged in urine. |
| Half-life | Terminal elimination half-life: 13-19 hours (mean 16 hours) for norethindrone; steady state achieved within 5-7 days. |
| Protein binding | Norethindrone: 61-67% bound to SHBG and albumin (55% to SHBG, 45% to albumin); ethinyl estradiol: 97-98% bound to albumin, not bound to SHBG. |
| Volume of Distribution | Norethindrone: Vd approximately 4 L/kg (range 2-6 L/kg), indicating extensive tissue distribution; ethinyl estradiol: Vd approximately 2-4 L/kg. |
| Bioavailability | Oral norethindrone: 45-65% due to first-pass metabolism; ethinyl estradiol: 38-48% oral bioavailability. |
| Onset of Action | Oral: Contraceptive effect requires 7 days of continuous dosing for full suppression of ovulation; if started on day 1 of menses, additional contraception not needed. |
| Duration of Action | 24 hours; daily dosing required to maintain contraceptive effect; withdrawal bleed occurs during placebo week. |
One tablet orally once daily, each tablet containing 0.035 mg ethinyl estradiol and 0.4 mg norethindrone, taken at the same time each day for 21 days followed by 7 days of placebo tablets.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Insufficient data for severe renal impairment (CrCl <30 mL/min); consider alternative contraception due to potential hormonal accumulation. |
| Liver impairment | Contraindicated in acute hepatic disease or severe hepatic impairment (Child-Pugh class C). Use with caution in mild to moderate impairment (Child-Pugh A or B); monitor liver function; consider alternative contraception. |
| Pediatric use | Not indicated for use before menarche. For post-menarche adolescents: same dosing as adults (one tablet daily). Safety and efficacy established in females of reproductive age. |
| Geriatric use | Not indicated for use in postmenopausal women. Efficacy for contraception not applicable; no dosing recommendations for this population. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MODICON 28 (MODICON 28).
| Breastfeeding | Safety: Small amounts of ethinyl estradiol and progestin (norethindrone) are excreted in breast milk. M/P ratio: Not established for this specific combination; ethinyl estradiol M/P ~0.2-0.4. May reduce milk production and alter milk composition. Not recommended during breastfeeding; alternative contraception advised. |
| Teratogenic Risk | FDA Pregnancy Category X. First trimester: increased risk of neural tube defects, congenital heart defects, and other malformations due to estrogen/progestin exposure. Second and third trimesters: associated with elevated risks of preterm birth, low birth weight, and neonatal complications. Use contraindicated in pregnancy. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptives. Risk increases with age and smoking intensity, especially in women over 35. Women should be strongly advised not to smoke.
| Serious Effects |
["Known or suspected pregnancy","Current or past history of thrombophlebitis or thromboembolic disorders","Cerebrovascular disease","Coronary artery disease","Known or suspected carcinoma of the breast","Carcinoma of the endometrium or other estrogen-dependent neoplasia","Undiagnosed abnormal genital bleeding","Cholestatic jaundice of pregnancy or jaundice with prior oral contraceptive use","Hepatic adenomas or carcinomas","Known or suspected liver disease","Heavy smoking (≥15 cigarettes/day) and age ≥35","Hypersensitivity to any component"]
| Precautions | ["Thrombotic disorders (thrombophlebitis, venous thromboembolism, cerebrovascular disease, myocardial infarction)","Hepatic disease (jaundice, hepatic adenomas)","Hypertension","Gallbladder disease","Carbohydrate and lipid effects","Ocular lesions (e.g., retinal thrombosis)","Headache (including migraine)","Menstrual irregularities/breakthrough bleeding","Depression","Reduced efficacy with enzyme-inducing drugs","Bone mineral density changes","Hereditary angioedema"] |
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| Fetal Monitoring | Monitor for signs of pregnancy with regular pregnancy tests. Assess for thromboembolic events, hypertension, and glucose intolerance. In case of accidental pregnancy, discontinue immediately and perform fetal ultrasound for anomalies. |
| Fertility Effects | Reversible suppression of ovulation. Return to fertility may be delayed up to 3-6 months after discontinuation. No permanent negative effect on fertility observed. |