Norethindrone dosing

Progestin-only contraceptives (Fig. 4) contain low-doses of progestins (e.g. 350 pg norethindrone or 75 pg norgestrel) that have to be administered daily without interruption. The lowest expected failure rate during the first year of use is 0.5%, while the typical failure rate amounts to 3%. Subdermal implants of norgestrel (216 mg) for sustained release provides for long-term (for up to 5 years) contraceptive effects characterized by failure rates of only 0.05%. Reliable contraception for 3 months can be achieved by an intramuscular injection of a crystalline suspension of 150 mg medroxyprogesterone acetate (Fig. 3) (failure rate 0.3%). 

Speroff L, Symons J, Kempfert N et al. (2000) Femhrt study investigators. The effect of varying low-dose combinations of norethindrone acetate and ethinyl estradiol (femhrt) on the frequency and intensity of vasomotor symptoms. Menopause7 383-390... 

Progestin-only oral contraceptive formulations consist of a low dose of either norethindrone or norgestrel... 

The minimum dose of continuously administered nor-ethindrone acetate needed to reduce significantly the incidence of endometrial hyperplasia associated with the use of 17-P-estradiol 1 mg/day has been investigated in a large, controlled, comparative study in 1146 women over 12 months (107). The results suggested that continuous norethindrone acetate at doses as low as 0.1 mg/day is fully effective, at least during the first year of treatment. 

Since oral contraceptive users sometimes need to be treated for vaginal candidiasis, the question arises which of the available treatments can be used without risk of impairing contraception. In a crossover placebo-con-trolled study, fluconazole 300 mg weekly for two cycles has been studied in 21 healthy women using Ortho-Novum 7/7/7 as a contraceptive (344). Fluconazole in this dose, which is twice that ordinarily recommended, produced small but statistically significant increases in the AUCo-24 for both ethinylestradiol (mean 24% increase) and norethindrone (mean 13%). The Cmax of ethinylestradiol was slightly, but just significantly, higher... 

Brody SA, Turkes A, Goldzieher JW. Pharmacokinetics of three bioequivalent norethindrone/mestranol-50 micrograms and three norethindrone/ethinyl estradiol-35 micrograms OC formulations are low-dose pills really lower Contraception 1989 40 269-284. 

Fig. 4 Computer simulation of a plasma level-time profile of norethindrone from fast-releasing tablet (—) and sustained release tablet (—), from a dose of 0.5 mg/tablet and an elimination half-life of 3 h.

The mutual pharmacokinetic interaction of nevirapine with ethinylestradiol + norethindrone has been studied in 10 women (26). After a single dose of ethinylestradiol -I- norethindrone, they took oral nevirapine 200 mg/day (days 2-15), followed by 200 mg bd (days 16-29) on day 30 they took another dose of ethinylestradiol + norethindrone. Steady-state nevirapine reduced the AUC of ethinylestradiol by 29% and significantly reduced its mean residence time and half-life. The AUC of norethindrone was significantly reduced by 18%, but there was no change in C ax, mean residence time, or half-life. The kinetics of nevirapine were not affected by the oral contraceptive. The authors attributed this interaction to increased clearance of ethinylestradiol and concluded that oral contraceptives should not be the primary method of birth control in women of child-bearing potential who are taking nevirapine. 

Combinations of estrogens (ethinyl estradiol, mestranol) with progestins (norgestrel, norethindrone) in varied dose, with mono-, bi-, and triphasic variants... 

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