LARIN 1/20
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LARIN 1/20 (LARIN 1/20).
Combination estrogen-progestin contraceptive; suppresses gonadotropins (FSH, LH) via negative feedback on hypothalamic-pituitary axis, inhibiting ovulation; increases cervical mucus viscosity, inhibiting sperm penetration; alters endometrial receptivity.
| Metabolism | Ethinyl estradiol: primarily metabolized by CYP3A4; undergoes first-pass metabolism in gut and liver. Norethindrone: primarily metabolized by reduction and conjugation; substrate of CYP3A4. |
| Excretion | Approximately 60% renal (30% norethindrone, 30% ethinyl estradiol metabolites) and 40% fecal (biliary excretion of conjugates). |
| Half-life | Norethindrone: 7.6 hours (range 5-14); Ethinyl estradiol: 13.2 hours (range 8-20). Clinical context: Steady-state achieved within 5-10 days. |
| Protein binding | Norethindrone: 61% (albumin, SHBG); Ethinyl estradiol: 97% (albumin). |
| Volume of Distribution | Norethindrone: 3.8 L/kg; Ethinyl estradiol: 2.8 L/kg. Indicates extensive tissue distribution. |
| Bioavailability | Oral: Norethindrone 64% (first-pass metabolism); Ethinyl estradiol 38-48% (first-pass metabolism). |
| Onset of Action | Oral: 1-3 days for contraceptive effect (ovulation suppression requires ≥7 days of consistent use). |
| Duration of Action | 24 hours (daily dosing required). Clinical note: Missed dose reduces efficacy; back-up contraception needed if >36-hour interval. |
One tablet (0.1 mg levonorgestrel/20 mcg ethinyl estradiol) orally once daily for 21 days followed by 7 placebo days.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Contraindicated in severe renal impairment (GFR <30 mL/min) due to potential fluid retention and metabolic acidosis. |
| Liver impairment | Contraindicated in acute hepatic disease, hepatic adenomas, or severe cirrhosis (Child-Pugh class C). No specific dose adjustments provided for mild to moderate impairment; use caution. |
| Pediatric use | Not indicated for use before menarche. For postmenarchal adolescents, same dosing as adults: one tablet orally once daily for 21 days followed by 7 placebo days. |
| Geriatric use | Not indicated for use after menopause. No specific dose adjustments in elderly; increased risk of thrombosis and hypoglycemia warrants caution. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LARIN 1/20 (LARIN 1/20).
| Breastfeeding | Small amounts of ethinyl estradiol and norethindrone pass into breast milk; combined OCs are generally not recommended during breastfeeding, especially in early lactation, as they may reduce milk quantity and quality. M/P ratio: Not established for LARIN 1/20; ethinyl estradiol M/P ratio is ~0.2-0.4, norethindrone M/P ratio ~0.1. Infants exposed via milk show no significant adverse effects, but theoretical risks include jaundice, breast enlargement, and long-term carcinogenicity. Use of progestin-only contraceptives is preferred. |
| Teratogenic Risk | LARIN 1/20 (norethindrone acetate/ethinyl estradiol) is contraindicated in pregnancy. First trimester: No increased risk of major birth defects from low-dose OCs in cohort studies, but an increased risk of cardiovascular malformations (e.g., VSD, TGA) and neural tube defects has been suggested in some studies; risk of oral cleft is not increased. Second/third trimesters: Use may increase risk of fetal hepatic adenoma, fetal feminization with androgenic progestins (norethindrone has minimal androgenicity), and potential for neonatal withdrawal bleeding or hormonal effects; no clear risk of pregnancy loss beyond baseline. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptives. Risk increases with age (especially >35 years) and with heavy smoking (≥15 cigarettes/day). Women who use combination hormonal contraceptives should not smoke.
| Serious Effects |
["Thrombophlebitis or thromboembolic disorders","History of deep vein thrombosis or pulmonary embolism","Cerebrovascular or coronary artery disease","Known or suspected breast cancer","Endometrial or other estrogen-dependent neoplasia","Undiagnosed abnormal genital bleeding","Cholestatic jaundice of pregnancy or jaundice with prior pill use","Hepatic adenoma or carcinoma","Known or suspected pregnancy","Hypersensitivity to any component","Heavy smoking (≥15 cigarettes/day) in women >35 years"]
| Precautions | ["Thrombotic disorders: discontinue if thrombophlebitis, thromboembolic, or vascular events occur","Carcinoma risk: increased risk of breast cancer; cervical cancer association","Hepatic effects: acute liver disease, liver tumors","Elevated blood pressure","Gallbladder disease","Carbohydrate/lipid metabolic effects","Ocular lesions: retinal thrombosis; discontinue if unexplained vision loss","Hereditary angioedema exacerbation","Chloasma","Pregnancy: discontinue if pregnancy occurs"] |
Loading safety data…
| Fetal Monitoring | Pregnancy test before initiation if pregnancy suspected. No routine fetal monitoring required if used inadvertently; if exposure occurs in first trimester, offer prenatal diagnostic testing (ultrasound at 18-20 weeks for structural anomalies; consider fetal echocardiography if concerns). Monitor maternal blood pressure and liver function if prolonged use during pregnancy (rare). |
| Fertility Effects | LARIN 1/20 suppresses ovulation via inhibition of gonadotropins; normal fertility returns within 1-3 months after discontinuation. No permanent impairment of fertility. Post-pill amenorrhea may occur in <1% of users, usually resolving spontaneously; evaluate if >6 months. No adverse effects on oocyte quality or long-term reproductive capacity. |