Potential Drug Interactions: Hormonal Contraceptives and Antiretroviral Drugs

Limited data from small, mostly unpublished studies suggest that some antiretroviral (ARV) therapies might alter the pharmacokinetics of combined oral contraceptives (COCs). Few studies have measured clinical outcomes. However, contraceptive steroid levels in the blood decrease substantially with ritonavir-boosted protease inhibitors. Such decreases have the potential to compromise contraceptive effectiveness. Some of the interactions between contraceptives and ARVs also have led to increased ARV toxicity. For smaller effects that occur with non-nucleoside reverse transcriptase inhibitors, clinical significance is unknown, especially because studies have not examined steady-state levels of contraceptive hormones. No clinically significant interactions have been reported between contraceptive hormones and nucleoside reverse transcriptase inhibitors.

Tables 1 and 2 summarize the evidence available about drug interactions between ARV therapies and hormonal contraceptives. For up-to-date, detailed information about human immunodeficiency virus (HIV) drug interactions, the following resources might be helpful:

 

TABLE 1. Drug interactions between COCs and ARV drugs*
ARV Contraceptive effects ARV effects
Nucleoside reverse transcriptase inhibitors (NRTIs)
Tenofovir disaproxil fumarate
EE ↔, NGM ↔ (1) Tenofovir ↔ (1)
Zidovudine
No data Zidovudine ↔ (2)
No change in viral load or CD4+ (2)
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Efavirenz EE ↑ (3), EE ↔ (4), NGM ↓ (4), LNG ↓ (4)
Pregnancy rate 2.6/100 woman-years in 1 study in which up to 80% used hormonal contraceptives (35% used COC) (5)
Efavirenz ↔ (3,4)
Etravirine EE ↔, NET ↔ (6) Etravirine ↑ (6)

Concurrent administration, generally safe and well tolerated (6)

Nevirapine EE ↔, NET ↔ (7) Nevirapine ↔ (7)
Protease inhibitors and ritonavir-boosted protease inhibitors
Atazanavir/ritonavir EE ↑, NET ↑ (8) No data
Darunavir/ritonavir EE ↓, NET ↔ (9) Darunavir ↔ (9)
Fosamprenavir/ ritonavir EE ↓ (10,11), NET ↓ (11) Amprenavir ↔, ritonavir ↑, Elevated liver transaminases (10)
Indinavir§ EE ↔, NET ↔ (12) No data
Lopinavir/ritonavir EE ↓, NET ↔ (13) No data
Nelfinavir EE ↓, NET ↔ (14) No data
Saquinavir§ No data Saquinavir ↔ (15,16)
Tipranavir/ritonavir EE↓ (17) ↑ Skin and musculoskeletal adverse events; possible drug hypersensitivity reaction (17)
* Abbreviations: COC = combined oral contraceptive; ARV = antiretroviral; EE = ethinyl estradiol; NGM = norgestimate; NNRTI = non-nucleoside reverse transcriptase inhibitor; LNG = levonorgestrel; NET = norethindrone. ↔, no change or change ≤30%; ↑, increase >30%; ↓, decrease >30%.

§ Saquinavir and indinavir are commonly given boosted by ritonavir, but there are no data on contraceptive interactions with the boosted regimens.

 

TABLE 2. Drug interactions between DMPA and ARV drugs*
ARV Contraceptive effects ARV effects
Nucleoside reverse transcriptase inhibitors (NRTIs)
Zidovudine No data Zidovudine ↔ (2)
No change in viral load
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Efavirenz MPA ↔ (18,19)
No ovulations during 3 cycles(18,19)
Pregnancy rate 2.6/100 woman-years in 1 study where up to 80% used hormonal contraceptives (65% used POIs) (5)
Efavirenz ↔ (18)
No change in viral load or CD4+, no grade 3- or 4-related adverse events§ (20)
Nevirapine MPA ↔ (18)
No ovulations during 3 cycles (18)
Nevirapine ↑ (18)
No change in viral load or CD4+, no grade 3- or 4-related adverse events§ (20)
Protease inhibitors and ritonavir-boosted protease inhibitors
Nelfinavir MPA ↔ (18) Nelfinavir ↔ (18)
No change in viral load or CD4+, no grade 3- or 4-related adverse events§ (20)
* Abbreviations: DMPA = depot medroxyprogesterone acetate; ARV = antiretroviral; NRTI = nucleoside reverse transcriptase inhibitor; NNRTI = non-nucleoside reverse transcriptase; MPA = medroxyprogesterone acetate; POI = progestin-only injectables. ↔, no change or change ≤30%; ↑, increase > 30%.

§ The trial applied the standardized National Institutes of Health Division of AIDS Table for Grading Severity of Adult and Pediatric Adverse Events, 2004 (http://rsc.tech-res.com/Document/safetyandpharmacovigilance/Table_for_Grading_Severity_of_Adult_Pediatric_Adverse_Events.pdfpdf iconexternal icon). Grade 3 events are classified as severe. Severe events are defined as symptoms that limit activity or might require some assistance; require medical intervention or therapy; and might require hospitalization. Grade 4 events are classified as life threatening. Life-threatening events include symptoms that result in extreme limitation of activity and require substantial assistance; require substantial medical intervention and therapy; and probably require hospitalization or hospice.

References

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