Clinical Manual for Management of the HIV-Infected Adult
2006 Edition

Section 3: Antiretroviral Therapy

Antiretroviral Medications and Oral Contraceptive Agents

July 2006

Background

This chapter highlights the interactions between currently available antiretroviral agents and oral contraceptives.

The oral contraceptives ethinyl estradiol and norethindrone may interact in complex ways with protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs). The mechanism of these interactions may be multifactorial and includes the activity of these agents on cytochrome P450 enzymes. Pharmacokinetic studies have shown changes (either increases or decreases) in levels of ethinyl estradiol and norethindrone in women who are taking certain PIs or NNRTIs. Other studies have shown decreases in levels of amprenavir (a PI) in women taking oral contraceptives.

The clinical significance of these drug interactions has not been evaluated thoroughly, but may cause oral contraceptive failure or antiretroviral failure, or medication toxicity, depending on whether drug levels are lowered or raised by the interacting drug.

Table 1 summarizes the available pharmacokinetic data. A more comprehensive review of oral and nonoral contraceptives for HIV-infected women can be found in the chapter Care of HIV-Infected Pregnant Women.

Table 1. Interactions between Antiretroviral Agents and Oral Contraceptives

Antiretroviral Agent Pharmacokinetic Changes with Oral Contraceptives Comments Protease Inhibitors Atazanavir (ATV, TAZ, Reyataz) EE AUC increased 48% NE AUC increased 110% Use lowest effective dose of each OC component and monitor for adverse effects. Consider alternative methods of contraception to avoid OC adverse effects. Fosamprenavir (FPV, Lexiva), Amprenavir (AMP, Agenerase) Cmin of EE/NE increased 32-45%; no significant change in AUC Amprenavir AUC decreased 22% and Cmin decreased 20% To avoid risk of ARV failure, do not coadminister amprenavir or fosamprenavir with OCs. Consider alternative methods of contraception. Indinavir (IDV, Crixivan) EE AUC increased 24% NE AUC increased 26% No dose adjustment is recommended. Lopinavir/ritonavir (LPV/r, Kaletra) EE AUC decreased 42% NE AUC decreased 17% Use of alternative or additional method of contraception is recommended. Nelfinavir (NFV, Viracept) EE AUC decreased 47% NE AUC decreased 18% Use of alternative or additional method of contraception is recommended to avoid contraceptive failure. Ritonavir (RTV, Norvir) EE AUC decreased 40% Use of alternative or additional method of contraception is recommended to avoid contraceptive failure. Saquinavir (SQV, Invirase, Fortovase) No data available regarding effect of SQV on EE or NE levels SQV kinetics not affected by OC Until more data are available alternative methods of contraception is recommended. Tipranavir/ritonavir (TPV/r, Aptivus) EE Cmax and AUC decreased approximately 50% Use of alternative or additional method of contraception is recommended to avoid contraceptive failure. Nonnucleoside Reverse Transcriptase Inhibitors Efavirenz (EFV, Sustiva) EE levels increased 37% No data available on NE component Use of alternative method of contraception is recommended to avoid OC side effects. Nevirapine (NVP, Viramune) EE AUC decreased 20% NE AUC decreased 20% Use of alternative or additional method of contraception is recommended to avoid contraceptive failure.

Key to abbreviations: EE = ethinyl estradiol; NE = norethindrone; AUC = area under the curve (drug concentration); Cmin = minimum concentration; Cmax = maximum concentration. Adapted from U.S. Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. May 4, 2006.

References

• U.S. Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. May 4, 2006. Available online at aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?GuidelineID=7.