MODICON 28
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | Ethinyl estradiol: 296.41 Da, Norethindrone: 298.42 Da |
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 | Contraindicated in first trimester due to risk of teratogenicity (neural tube defects, cardiovascular anomalies) associated with estrogen/progestin exposure. |
| 2nd trimester | Not recommended; may increase risk of venous thromboembolism and adverse fetal outcomes. Limited data suggests possible association with fetal genital abnormalities. |
| 3rd trimester | Avoid in third trimester due to potential adverse effects on fetal development and neonatal complications (e.g., jaundice, respiratory distress). |
Clinical note
Comprehensive clinical and safety monograph for MODICON 28 (MODICON 28).
| Placental transfer | Extensive; ethinyl estradiol and norethindrone cross the placenta readily, achieving fetal plasma concentrations similar to maternal levels. |
| Breastfeeding | Estrogen and progestin are excreted in breast milk in small amounts; may reduce milk production and quality. Use caution and prefer progestin-only contraceptives. Observe infant for jaundice, weight gain, and growth. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
■ 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 |
Pregnancy (known or suspected)Undiagnosed abnormal genital bleedingKnown or suspected breast cancerActive liver disease or hepatic tumorsHistory of deep vein thrombosis or pulmonary embolismCerebrovascular or coronary artery diseaseUncontrolled hypertensionMigraine with focal neurological symptoms (age >=35)Diabetes with vascular involvementKnown thrombogenic mutations (e.g., Factor V Leiden)
| 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 |
| Food/Dietary | Grapefruit and grapefruit juice may increase ethinyl estradiol levels by inhibiting CYP3A4, but the effect is variable; advise caution or avoid concurrent intake. No other significant food interactions are known. High-fat meals may delay absorption but do not reduce overall efficacy. |
| Clinical Pearls | MODICON 28 is a combined oral contraceptive containing ethinyl estradiol 0.035 mg and norethindrone 0.5 mg. It is crucial to counsel patients on the importance of taking the pill at the same time daily to maintain consistent hormone levels. The regimen includes 21 active pills followed by 7 placebo pills; during the placebo week, withdrawal bleeding typically occurs. For missed pills: if one pill is missed, take it as soon as remembered and continue schedule; if two or more are missed, take the most recent missed pill and use backup contraception for 7 days. Consider potential drug interactions with antibiotics, anticonvulsants (e.g., carbamazepine, phenytoin), and St. John's wort, which may reduce contraceptive efficacy. Smoking increases risk of serious cardiovascular events, especially in women over 35. Monitor blood pressure at baseline and periodically. Caution in patients with history of thromboembolic disorders, migraine with aura, hypertension, or liver disease. |
| Patient Advice | Take one pill daily at the same time, preferably after an evening meal or at bedtime to minimize nausea. · The pack contains 21 active (hormone) pills and 7 placebo (reminder) pills; withdrawal bleeding usually occurs during the placebo week. · If you miss a pill, refer to the package insert instructions; use backup contraception (e.g., condoms) if needed. · Use additional non-hormonal contraception during the first 7 days of starting the pill if switching from another method. · Seek immediate medical attention if you experience symptoms of a blood clot, such as sudden leg pain or swelling, chest pain, shortness of breath, or severe headache. · This medication does not protect against sexually transmitted infections (STIs); use condoms for STI prevention. · Inform your healthcare provider of all medications and supplements you take, especially antibiotics, anticonvulsants, and St. John's wort. · Avoid smoking, especially if over 35, as it increases the risk of serious side effects. |
Loading safety data…