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Database of Antiretroviral Drug Interactions

Interactions between Hormonal agents and Antiretrovirals

Interactions with Ethinyl estradiol/norethindrone acetate
Antiretroviral (ARV)Dose of ARVDose of Ethinyl estradiol/norethindrone acetateEffect on ARV LevelsEffect on Ethinyl estradiol/norethindrone acetate LevelsPotential Clinical EffectsMechanism of InteractionManagement
Amprenavir60
(APV)(Agenerase)
1200 mg BID x 28 days0.035 mg ethinyl estradiol/1 mg norethindrone x 1 cycleAmprenavir AUC: decreased 22%; Cmin: decreased 20%Ethinyl estradiol Cmin: increased 32%; Norethindrone AUC: increased 18%; Cmin: increased 45%Unknown effect on birth controlNot established

Dose adjustment not established; may need to use alternative method of birth control

Alternative Agents:
Barrier devices, condoms

Atazanavir4
(ATV)(Reyataz)
400 mg QD x 14 days1 tab QD (7/7/7)Not studiedNorethindrone Cmax: increased 67%; AUC: increased 110%; Cmin: increased 262%; Ethinyl estradiol AUC: increased 48%; Cmax: no significant change; Cmin: increased 91%Increased norethindrone and ethinyl estradiol effectsInhibition of UGT 1A1 by atazanavir

Use oral contraceptive that contains no more than 30 mcg of ethinyl estradiol or recommend an alternative contraceptive method. Oral contraceptives containing less than 25mcg of ethinyl estradiol or progestins other than norethindrone or norgestimate have not been studied.

Alternative Agents:
Non hormonal contraceptive method, barrier devices, condoms

Darunavir161, 365
(DRV)(Prezista)
600 mg BID with ritonavir 100 mg BIDEthinyl estradiol (EE) 35 mcg/ Norethindrone (N) 1.0 mg QD x 21 daysNo significant effectEthinyl estradiol AUC: decreased 37-48%; Cmax: decreased 32%; Cmin decreased 62%; Norethindrone AUC decreased 14%- 34%; Cmax no significant change; Cmin decreased 30%.Decreased ethinyl estradiol and norethindrone effects (eg, contraceptive failure)Induction of CYP450 3A4 by ritonavir

Use alternative contraceptive method

Alternative Agents:
Barrier devices; Condoms

Efavirenz90
(EFV)(Sustiva)
400 mg x 10 daysEthinyl estradiol 50 mcg x 1 doseNo significant changeNo significant change--

No dose adjustment necessary

Etravirine405
(ETR)(Intelence)
-0.035 mg EE/1 mg NE QD- Ethinyl estradiol AUC: increased 22%; Cmax: increased 33%; Norethindrone Cmin: decreased 22%--

No dose adjustment necessary

Antiretroviral (ARV)Dose of ARVDose of Ethinyl estradiol/norethindrone acetateEffect on ARV LevelsEffect on Ethinyl estradiol/norethindrone acetate LevelsPotential Clinical EffectsMechanism of InteractionManagement
Indinavir16, 254
(IDV)(Crixivan)
800 mg Q8H x 1 week0.035 mcg ethinyl estradiol/1 mg norethindrone QD x 1 weekNot studiedEthinyl estradiol AUC: increased 24%; norethindrone AUC: increased 26%--

No dose adjustment necessary

Lopinavir/ritonavir78
(LPV/r)(Kaletra)
400 mg/100 mg BID x 14 daysEthinyl estradiol 35 mcg QD x 21 days- Ethinyl estradiol AUC: decreased 42%; Cmax: decreased 41%; Cmin: decreased 58%Decreased ethinyl estradiol effects (eg, contraceptive failure)Induction of CYP450 3A4 by ritonavir

Use alternative contraceptive method

Alternative Agents:
Barrier devices Condoms

Lopinavir/ritonavir78
(LPV/r)(Kaletra)
400 mg/100 mg BID x 14 daysNorethindrone 1 mg QD x 21 days- Norethindrone AUC: decreased 17%; Cmax: decreased 16%; Cmin: decreased 32%Decreased norethindrone effects (eg, contraceptive failure)Induction of CYP450 3A4 by ritonavir

Use alternative contraceptive method

Alternative Agents:
Barrier devices Condoms

Nelfinavir254, 24
(NFV)(Viracept)
750 mg Q8H x 7 daysEthinyl estradiol (EE) 35 mcg/ Norethindrone (N) 0.4 mg QD x 15 days- Ethinyl estradiol AUC: decreased 47%; Cmax: decreased 28%;Norethindrone AUC: decreased 18%; Cmax: no significant changeContraceptive failureInduction of glucuronyl transferase by nelfinavir; inhibition of CYP450 3A4 by nelfinavir

Use alternative method of birth control

Alternative Agents:
Condoms; barrier methods

Nevirapine370
(NVP)(Viramune)
200 mg BID x 30 daysEthinyl estradiol 0.035 mg/Norethindrone 1 mg QD x 30 daysNo significant changeEthinyl estradiol: AUC decreased 23%; half-life: decreased 44%; Norethindrone: AUC decreased 18%; half-life: decreased 15%Possible contraceptive failureInduction of CYP450 3A4 by nevirapine

Avoid coadministration; additional contraceptive measures may be needed

Nevirapine369, 95
(NVP)(Viramune)
200 mg QD x 2 weeks then 200 mg BIDEthinyl estradiol 0.035 mg/Norethindrone 1 mg x 1 doseNo significant changeEthinyl estradiol AUC: decreased 19%; Cmax: no significant changeNorethindrone AUC: decreased 18%Possible contraceptive failureInduction of CYP450 3A4 by nevirapine

Use alternative contraceptive method

Alternative Agents:
Barrier devices; Condoms

Antiretroviral (ARV)Dose of ARVDose of Ethinyl estradiol/norethindrone acetateEffect on ARV LevelsEffect on Ethinyl estradiol/norethindrone acetate LevelsPotential Clinical EffectsMechanism of InteractionManagement
Rilpivirine567
(RPV)(Edurant)
25 mg QD0.035 mg QD ethinyl estradiol with 1 mg norethindrone QDNo significant changeEthinyl estradiol Cmax: increased 17%; Norethindrone: no significant change--

No dose adjustment necessary

Ritonavir368, 55
(RTV)(Norvir)
500 mg Q12H50 mcg x 2 doses- Ethinyl estradiol Cmax: decreased 32%; AUC: decreased 41%Decreased oral contraceptive effectivenessInduction CYP450 3A4 by ritonavir

Use alternative contraceptive method

Alternative Agents:
Barrier devices; Condoms

Saquinavir366
(SQV)(Fortovase, Invirase)
600 mg saquinavir hard gel caps on days 1 and 220.03 mg ethinyl estradiol/0.075 mg gestodene QD on days 4-22No significant changeNo significant change--

No dose adjustment necessary

Tenofovir disoproxil fumarate367
(TDF)(Viread)
300 mg QD1 tab QDNo significant changeNo significant change--

No dose adjustment necessary

Tipranavir154
(TPV)(Aptivus)
500 mg BID with 100 mg ritonavir BID x 12 days0.035 mg/1 mg x 1 dose on day 1 and day 15Tipranavir Cmin: decreased 26%; Ritonavir AUC: decreased 22%; Cmax: decreased 26%; Cmin: decreased 41%Ethinyl estradiol AUC: decreased 48%; Cmax: decreased 48%Decreased ethinyl estradiol/norethindrone effectsPossible induction of CYP450 3A4 by tipranavir

Dose adjustment not established; backup contraceptive method recommended

Tipranavir154
(TPV)(Aptivus)
750 mg BID with 200 mg ritonavir BID x 12 days0.035 mg/1 mg x 1 dose on day 1 and day 15Ritonavir Cmin: decreased 20%;Ethinyl estradiol AUC: decreased 42%; Cmax: decreased 51%; Norethindrone AUC: increased 26%Decreased ethinyl estradiol/norethindrone effectsPossible induction of CYP450 3A4 by tipranavir

Dose adjustment not established; backup contraceptive method recommended

"-" indicates that there are no data available
Interactions with Ethinyl estradiol/norgestimate
Antiretroviral (ARV)Dose of ARVDose of Ethinyl estradiol/norgestimateEffect on ARV LevelsEffect on Ethinyl estradiol/norgestimate LevelsPotential Clinical EffectsMechanism of InteractionManagement
Atazanavir727
(ATV)(Reyataz)
300 mg QD with 100 mg atazanavir QD--Ethinyl estradiol AUC: decreased 19%; Cmax: decreased 16%; Cmin: decreased 37% 17-deacetyl norgestimate AUC: increased 85%; Cmax: increased 68%; Cmin: increased 102%--

Use oral contraceptive containing at least 35 mcg of ethinyl estradiol. Oral contraceptives containing progestins other than norethindrone or norgestimate have not been studied.

Alternative Agents:
Non-hormonal contraceptives, barrier devices, condoms

Bictegravir759
(Biktarvy)
75 mg daily0.025 mg daily with 0.180/0.215/0.250 norgestimate dailyNot studied Ethinyl estradiol Cmax inccreased 15%; AUC increased 4%; Cmin increased 5%. Norelgestromin (norgestimate) Cmax increased 23%; AUC increased 8%; Cmin increased 10%.--

No dose adjustment necessary

Dolutegravir641
(Tivicay)
50 mg BID0.035 mg ethinyl estradiol-No significant change--

No dose adjustment necessary

Efavirenz421
(EFV)(Sustiva)
600 mg QHS0.025 mg ethinyl estradiol/0.25 mg norgestimate-Ethinyl estradiol: no significant change; Norgestromin AUC: decreased 64%; Cmax: decreased 46%; Cmin: decrased 82%Decreased effects of ethinyl estradiol and norgestimateInduction of CYP450 3A4 by efavirenz

Do not coadminister; use other forms of birth control

Elvitegravir/cobicistat623
(Genvoya, Stribild)
150/150 mg0.18/0.215/0.250 mcg norgestimate-Norgestimate AUC: increased 126%; Cmin: increased 167%; Ethinyl estradiol AUC: decreased 25%; Cmin: decreased 44%Increased norgestimate effects; decreased ethinyl estradiol effects-

Use with caution; alternate form of contraception recommended

Tenofovir disoproxil fumarate430
(TDF)(Viread)
300 mg QD1 tab QD- Ethinyl estradiol: no significant effect; Deacetyl norgestimate: no significant effect--

No dose adjustment necessary

"-" indicates that there are no data available
Interactions with Levonorgestrel
Antiretroviral (ARV)Dose of ARVDose of LevonorgestrelEffect on ARV LevelsEffect on Levonorgestrel LevelsPotential Clinical EffectsMechanism of InteractionManagement
Efavirenz449
(EFV)(Sustiva)
600 mg QHS0.75 mg x 1Not studiedLevonorgestrel AUC: decreased 58%; Cmax: decreased 45%; Cmin: decreased 71%; half-life: decreased 47%Decreased levonorgestrel effectsInduction of levonorgestrel metabolism by efavirenz

Use backup form of birth control (e.g. barrier)

"-" indicates that there are no data available
Interactions with Medroxyprogesterone acetate
Antiretroviral (ARV)Dose of ARVDose of Medroxyprogesterone acetateEffect on ARV LevelsEffect on Medroxyprogesterone acetate LevelsPotential Clinical EffectsMechanism of InteractionManagement
Efavirenz393
(EFV)(Sustiva)
-150 mgEfavirenz AUC: no significant changeProgesterone levels: no significant change--

No dose adjustment necessary

Lopinavir/ritonavir683
(LPV/r)(Kaletra)
400/100 mg BID150 mgLopinavir: no significant change; Ritonavir: no significant changeMedroxyprogesterone acetate AUC: increased 46%; Cmax: increased 65%--

No dose adjustment necessary

Nelfinavir393
(NFV)(Viracept)
-150 mgNelfinavir AUC: no significant change; M8 AUC: no significant changeProgesterone levels: no significant change--

No dose adjustment necessary

Nevirapine393
(NVP)(Viramune)
-150 mgNevirapine AUC: no significant changeProgesterone levels: no significant change--

No dose adjustment necessary

"-" indicates that there are no data available
Interactions with Norelgestromin
Antiretroviral (ARV)Dose of ARVDose of NorelgestrominEffect on ARV LevelsEffect on Norelgestromin LevelsPotential Clinical EffectsMechanism of InteractionManagement
Dolutegravir641
(Tivicay)
50 mg BID0.25 mg-No significant change--

No dose adjustment necessary

"-" indicates that there are no data available
Interactions with Norethindrone
Antiretroviral (ARV)Dose of ARVDose of NorethindroneEffect on ARV LevelsEffect on Norethindrone LevelsPotential Clinical EffectsMechanism of InteractionManagement
Nelfinavir402
(NFV)(Viracept)
750 mg Q8H x 7 days0.4 mg QD x 15 days-Norethindrone AUC: decreased 18%--

Use alternative method of birth control

Tipranavir154
(TPV)(Aptivus)
500 mg BID with 100 mg ritonavir BID1 mg x 1 dose-No significant change--

No dose adjustment necessary

Tipranavir154
(TPV)(Aptivus)
750 mg BID with 200 mg ritonavir BID x 21 doses1 mg x 1 dose-Norethindrone AUC: increased 27%--

No dose adjustment necessary

"-" indicates that there are no data available
Interactions with Norgestimate/ethinyl estradiol
Antiretroviral (ARV)Dose of ARVDose of Norgestimate/ethinyl estradiolEffect on ARV LevelsEffect on Norgestimate/ethinyl estradiol LevelsPotential Clinical EffectsMechanism of InteractionManagement
Elvitegravir/cobicistat715
(Genvoya, Stribild)
150/150 mg0.180/0.215/ 0.250 norgestimate once daily with 0.025 ethinyl estradiol once daily-Norgestimate AUC increased 2.6-fold. Ethinyl estradiol AUC decreased 25% and Cmin decreased 44%Potential increased risk of progestin adverse effects (insulin resistance, dyslipidemias, acne, venous thromboembolism)-

Weigh risks and benefits of coadministration and consider alternative contraceptive method.

Elvitegravir/ritonavir-boosted protease inhibitor
-- No clinically significant effect on antiretrovirals expected. Not studied; possible decreased levels of ethinyl estradiol and norethindrone. Possible loss of hormonal contraceptive efficacy-

With atazanavir/ritonavir, oral contraceptive should contain at least 35 mcg of ethinyl estradiol and only norethindrone has been studied. For other ritonavir boosted PIs recommend alternative or additional contraceptive method.

"-" indicates that there are no data available
 4:Tackett D, Child M, Agarwala S, et al. Atazanavir: a summary of two pharmacokinetic drug interaction studies in healthy subjects [abstract #543]. 10th Conference on Retroviruses and Opportunistic Infections; 2003 February 10-14; Boston, Massachusetts.
 16:Crixivan [package insert]. Whitehouse Station, NJ: Merck & Co., Inc.; Oct 2005.
 24:Viracept [package insert]. La Jolla, CA: Agouron Pharmaceuticals, Inc.; Sept 2004.
 55:Norvir [package insert]. North Chicago, IL: Abbott Laboratories, 2008.
 60:Agenerase [package insert]. Research Triangle Park, NC: Glaxo Wellcome Inc; 2004.
 78:Kaletra [package insert]. North Chicago, IL: Abbott Laboratories; Oct 2005.
 90:Sustiva [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; Dec 2011.
 95:Viramune [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; Nov 2005.
 154:Aptivus [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; Nov 2005.
 161:Prezista [package insert]. Raritan, NJ: Tibotec Therapeutics Inc.; April 2010.
 254:CDC. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. Jan 28, 2000. [AIDS Treatment Information Service: Current Treatment] Available at: http://www.hivatis.org/trtgdlns.html.
 365:Sekar V, Lefebvre E, Guzman SS, et al. Pharmacokinetic interaction between ethinyl estradiol, norethindrone and darunavir with low dose ritonavir in healthy women. Antivir Ther 2008; 13: 563-9.
 366:Frohlich M, Burhenne J, Martin-Facklam M, et al. Oral contraception does not alter single dose saquinavir pharmacokinetics in women. Br J Clin Pharmacol 2004;57:244-52.
 367:Kearney BP, Isaacson E, Sayre J, et al. Tenofovir DF and oral contraceptives: lack of a pharmacokinetic drug interaction [abstract #A-1618]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2003 September 14-17; Chicago, Illinois.
 368:Ouellet D, Hsu A, Qian J, et al. Effect of ritonavir on the pharmacokinetics of ethinyl estradiol in healthy female volunteers. Br J Clin Pharmacol 1998;46:111-16.
 369:Leitz G, Mildvan D, McDonough M, et al. Nevirapine (Viramune) and ethinyl estradiol/noethindrone [Ortho-Novum 1/35 (21 pack) EE/NET] interaction study in HIV-1 infected-women [abstract #89]. 7th Conference on Retroviruses and Opportunistic Infections; 2000 Jan 31-Feb 4; San Francisco, California.
 370:Mildvan D, Yarrish R, Marshak A, et al. Pharmacokinetic interaction between nevirapine and ethinyl estradil/norethindrone when adminstered concurrently to HIV-infected women. J Acq Immune Def Syn 2002;29:471-7.
 393:Cohn SE, Watts D, Lertora J, et al. An open-label, non-randomized study of the effect of depo-medroxyprogesterone acetate on the pharmacokinetics of selected protease inhibitors and non-nucleoside reverse transcriptase inhibitors therapies among HIV-infected women [abst. #82} 12th Conference on Retroviruses and Opportunistic Infections; 2005 February 22-25; Boston, Massachusetts.
 402:Viracept [package insert]. La Jolla, CA: Agouron Pharmaceuticals, Inc.; Sept 2004.
 405:Intelence [package insert]. Raritan, NJ: Tibotec Therapeutics; 2010.
 421:Sevinsky H, Eley T, He B, et al. Effect of efavirenz on the pharmacokinetics of ethinyl estradiol and norgestimate in healthy female subjects [abstract A-958]. 48th ICAAC/IDSA Annual Meeting 2008; Oct 25-28; Washington, D.C.
 430:Kearney BP and Mathias A. Lack of effect of tenofovir disoproxil fumarate on pharmacokinetics of hormonal contraceptives. Pharmacother 2009; 29: 924-29.
 449:Carten M, Kiser J, Kwara A, et al. Pharmacokinetic interactions between the hormonal emergency contraception, levonorgestrel and efavirenz [abstract 934]. 17th Conference on Retroviruses and Opportunistic Infections; 2010 Feb 16-18; San Francisco, California.
 567:Edurant [package insert]. Raritan, NJ: Tibotec Therapeutics Inc.; May 2011.
 623:Stribild [package insert]. Foster City, CA: Gilead Sciences, Inc.; August 2012.
 641:Tivicay [package insert]. Research Triangle Park, NC: Viiv Healthcare; Sept 2013.
 683:Cohn SE, Luque AE, Park J-G, et al. ACTG Study A5283: pharmacokinetic study of depot medroxyprogesterone acetate in HIV-infected women on lopinavir/ritonavir {poster 514LB]. Conference on Retroviruses and Opportunistic Infections; 2014 March 3-6; Boston, Massachusetts.
 715: Stribild [package insert]. Foster City, CA: Gilead Sciences, Inc.; Feb 2016
 727:Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf.
 759:Biktarvy [package insert]. Foster City, CA: Gilead Sciences, 2018