Comparative Pharmacology
Head-to-head clinical analysis: LEVONORGESTREL versus NORETHINDRONE AND ETHINYL ESTRADIOL 7 14.
Peer-Reviewed Evidence
Head-to-head clinical analysis: LEVONORGESTREL versus NORETHINDRONE AND ETHINYL ESTRADIOL 7 14.
LEVONORGESTREL vs NORETHINDRONE AND ETHINYL ESTRADIOL (7/14)
Comparing the clinical profiles, pharmacokinetic behaviors, and safety indices of these two therapeutic agents.
Synthetic progestin that suppresses gonadotropin release (GnRH, LH, FSH) via negative feedback on the hypothalamic-pituitary-ovarian axis; inhibits ovulation, thickens cervical mucus, and alters endometrial lining.
Norethindrone is a progestin that suppresses gonadotropin release, preventing ovulation. Ethinyl estradiol is an estrogen that provides negative feedback on the hypothalamic-pituitary axis, further inhibiting ovulation. The combination also alters cervical mucus and endometrial lining to impede fertilization and implantation.
For emergency contraception: 1.5 mg orally as a single dose or 0.75 mg orally 12 hours apart. For hormonal contraception: 0.03 mg to 0.05 mg orally once daily in combined oral contraceptives; for progestin-only oral contraceptive (mini-pill): 0.03 mg orally once daily. For intrauterine system (IUD): 52 mg intrauterine device inserted for up to 5 years.
One tablet (norethindrone 0.5 mg/ethinyl estradiol 35 mcg) orally once daily for 21 days (7 active tablets of norethindrone 0.5 mg/ethinyl estradiol 35 mcg followed by 14 active tablets of norethindrone 1 mg/ethinyl estradiol 35 mcg). Start on day 1 of menstrual cycle.
None Documented
Clinical Note
moderateLevonorgestrel + Sulfisoxazole
"The metabolism of Sulfisoxazole can be decreased when combined with Levonorgestrel."
Clinical Note
moderateLevonorgestrel + Erythromycin
"The metabolism of Erythromycin can be decreased when combined with Levonorgestrel."
Clinical Note
moderateLevonorgestrel + Cyclosporine
"The metabolism of Cyclosporine can be decreased when combined with Levonorgestrel."
Clinical Note
moderateLevonorgestrel + Fluconazole
None Documented
Terminal half-life: 24-30 hours (range 11-45 hours). This prolonged half-life supports once-daily or extended-cycle dosing in contraceptive formulations.
Norethindrone: 8-11 hours; Ethinyl estradiol: 17-27 hours. Achieves steady state within 5-10 days, permitting once-daily dosing.
Renal: 45-60% (metabolites), Fecal: 32-45% (unchanged and metabolites). Biliary excretion contributes to fecal elimination.
Norethindrone: ~50% renal, ~50% fecal; Ethinyl estradiol: ~50% renal, ~50% fecal, with enterohepatic circulation.
Category C
Category D/X
Progestin
Progestin
"The metabolism of Fluconazole can be decreased when combined with Levonorgestrel."