Efavirenz significantly reduces levels of some oral contraceptives
Polly Clayden, HIV i-Base
A PK study evaluated the effect of co-administration of EFV 600 mg on an ethinylestradiol (EE) and norgestimate (NGM)-containing oral contraceptive (OC).
This was an open-label, 3-period, single-sequence study conducted in healthy female volunteers. Women received Ortho Tri-Cyclen® LO once nightly (QHS) on Days 1 – 28 (period 1, n=28), Ortho Cyclen® QHS on Days 29 – 56 (period 2, n=23) and Ortho Cyclen with EFV 600 mg QHS on Days 57 – 70 (period 3, n=21).
The investigators determined noncompartmental PK. Adjusted geometric mean ratios (GMR) and 90% confidence intervals (CI) for the PK of EE and the major active metabolite of NGM, norelgestromin (NGMN), were estimated. They also conducted a similar evaluation of the secondary active metabolite levonorgestrel (LNG) PK in a small group of women (n=6). Serum progesterone (PG) levels were determined on Days 18, 46 and 74.
Comparing, period 3 to period 2, the investigators found that EFV had no effect on EE Cmax or AUC with GMRs (90% CI) of 1.06 (0.95 – 1.19) and 0.90 (0.80 – 1.01), respectively. EFV significantly decreased NGMN Cmax and AUC with GMRs (90% CI) of 0.54 (0.48-0.61) and 0.36 (0.33-0.38), respectively; LNG exposures (N=6) were also significantly decreased, with AUC GMR (90% CI) of 0.17 (0.13-0.21). PG levels were similar across periods.
The investigators concluded that these results reinforce the need for additional methods of barrier contraception when taking OC and EFV together.
Ref: Sevinsky H, Eley T, He B et al. Effect of efavirenz on the pharmacokinetics of ethinyl estradiol and norgestimate in healthy female subjects. 48th ICAAC, 25-28 October 2008. Washington. Abstract A-958.