Objectives. Compare the Plan B levonorgestrel (LNG) area under the concentration- time curve (AUC12) prior to and with efavirenz (EFV). Design. Prospective, open-label, single-arm, equivalence study. Methods. Healthy HIV-negative subjects underwent 12？hr intensive pharmacokinetic (PK) sampling following single dose LNG alone and after 14 days of EFV. Geometric means, Geometric Mean Ratios, and 90% confidence intervals (CI) are reported for PK Parameters. T-tests were utilized. Clinical parameters and liver function tests (LFTs) were assessed. Results. 24 women enrolled and 21 completed the study. With EFV, LNG AUC12 was reduced 56% (95% CI: 49%, 62%) from 42.9 to 17.8？ng*hr/mL, and maximum concentration ( ) was reduced 41% (95% CI: 33%, 50%) from 8.4 to 4.6？ng/mL. LNG was well tolerated with no grade 3 or 4 treatment-related toxicities. Conclusions. EFV significantly reduced LNG exposures. Higher LNG doses may be required with EFV. These results reinforce the importance of effective contraception in women taking EFV. 1. Introduction The majority of women with human immunodeficiency virus ？1 (HIV) are of reproductive age and may use an efavirenz- (EFV-) containing antiretroviral (ARV) regimen [1, 2]. EFV is a nonnucleoside reverse transcriptase inhibitor (NNRTI) indicated in combination with other antiretroviral agents for the treatment of HIV [3]. EFV is an FDA pregnancy category D drug based on animal studies and human case reports of fetal neural tube defects [3–6]. Thus, preventing pregnancy is critical in HIV-infected women receiving EFV. Pregnancy rates for HIV-infected women range from 6.0 to 8.2 pregnancies per 100 person-years, and in 2001, 49% of all pregnancies in the United States were unintended [7–9]. Women with HIV not desiring pregnancy are advised to use dual methods of contraception to prevent pregnancy and HIV transmission to their partners. Some women use emergency hormonal contraception to prevent pregnancy after unprotected sex or contraceptive failure (condom breakage). Plan B is a levonorgestrel- (LNG-) containing emergency contraceptive pill indicated for pregnancy prevention following unprotected intercourse or a known or suspected contraceptive failure [10]. It is taken as soon as possible within 72 hours after unprotected intercourse either as a single dose (LNG 1.5？mg) or as two doses (0.75？mg) taken twelve hours apart. LNG use for emergency hormonal contraception has been shown to reduce pregnancy rates by 85% [11]. The mechanism of action of Plan B is not fully elucidated. It may inhibit ovulation, fertilization, or
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