Clinical Manual for Management of the HIV-Infected ... - myCME.com

Section 3—Antiretroviral Therapy | 3–51
Antiretroviral Medications and Oral Contraceptive Agents
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
Table 1. Interactions between Antiretroviral Agents and Oral Contraceptives
Antiretroviral Agent Pharmacokinetic Changes with
Oral Contraceptives
Protease Inhibitors
Atazanavir (ATV, TAZ, Reyataz) • EE AUC increased 48%
• NE AUC increased 110%
Fosamprenavir (FPV, Lexiva),
Amprenavir (AMP, Agenerase)
•
•
C min of EE/NE increased 32-45%; no
significant change in AUC
Amprenavir AUC decreased 22% and C min
decreased 20%
Indinavir (IDV, Crixivan) • EE AUC increased 24%
• NE AUC increased 26%
Lopinavir/ritonavir (LPV/r, Kaletra) • EE AUC decreased 42%
• NE AUC decreased 17%
Nelfinavir (NFV, Viracept) • EE AUC decreased 47%
• NE AUC decreased 18%
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.
Comments
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Use lowest effective dose of each OC component and monitor for adverse effects.
Consider alternative methods of contraception to avoid OC adverse effects.
To avoid risk of ARV failure, do not coadminister amprenavir or fosamprenavir with
OCs.
Consider alternative methods of contraception.
No dose adjustment is recommended.
Use of alternative or additional method of contraception is recommended.
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 C and AUC decreased approximately • Use of alternative or additional method of contraception is recommended to avoid
max
50%
contraceptive failure.
Nonnucleoside Reverse Transcriptase Inhibitors
Efavirenz (EFV, Sustiva) • EE levels increased 37%
• No data available on NE component
Nevirapine (NVP, Viramune) • EE AUC decreased 20%
• NE AUC decreased 20%
•
•
Use of alternative method of contraception is recommended to avoid OC side
effects.
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); C min = minimum concentration; C max = 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. October 10, 2006.