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Database of Antiretroviral Drug Interactions

Interactions with Clarithromycin and Antiretrovirals

Antiretroviral (ARV)Dose of ARVDose of ClarithromycinEffect on ARV LevelsEffect on Clarithromycin LevelsPotential Clinical EffectsMechanism of InteractionManagement
Amprenavir361, 60
(APV)(Agenerase)
1200 mg BID x 7 doses500 mg BID x 7 dosesAmprenavir Cmax: increased 15%; AUC: increased 18%; Cmin: increased 39%Clarithromycin Cmax: no significant change; AUC: no significant change;14-hydroxy clarithromycin Cmax: decreased 32%; AUC: decreased 35%-Inhibition of CYP450 3A4 by amprenavir

No dose adjustment necessary

Atazanavir363
(ATV)(Reyataz)
400 mg QD on days 1-10500 mg BID on days 7-11 and 18-21Atazanavir AUC: increased 28%; Cmax: no significant change; Cmin: increased 91%Clarithromycin AUC: increased 94%; Cmax: increased 50%; Cmin: decreased 62%; 14-hydroxyclarithromycin AUC: decreased 70%; Cmax: decreased 72%; Cmin: increased 164%Increased clarithromycin effects. May cause QTc prolongation.Inhibition of CYP450 3A4 by atazanavir

Reduce clarithromycin dose by 50%

Alternative Agents:
azithromycin

Atazanavir/cobicistat755
(others)(Evotaz)
--Not studied; Potentially increased effects Not studied; Potentially increased effects--

Avoid combination if possible; consider alternative antibiotics

Alternative Agents:
azithromycin

Darunavir161
(DRV)(Prezista)
400 mg BID with ritonavir 100 mg BID500 mg BIDDarunavir Cmax: decreased 17%Clarithromycin AUC: increased 57%--

Monitor for clarithromycin-related toxicities or consider alternative macrolide. Reduce clarithromycin dose by 50% in patients with CrCl 30– 60 mL/min.Reduce clarithromycin dose by 75% in patients with CrCl <30 mL/min.

Alternative Agents:
Azithromycin

Delavirdine88
(DLV)(Rescriptor)
300 mg TID500 mg BIDDelavirdine AUC: increased 44%Clarithromycin AUC: increased 100%;14-hydroxy clarithromycin AUC: decreased 75%Not studiedInhibition of CYP450 3A4 and 2C9 by delavirdine

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Antiretroviral (ARV)Dose of ARVDose of ClarithromycinEffect on ARV LevelsEffect on Clarithromycin LevelsPotential Clinical EffectsMechanism of InteractionManagement
Efavirenz90
(EFV)(Sustiva)
400 mg x 7 days500 mg Q12H x 7 daysNo significant changeClarithromycin AUC: decreased 39%; Cmax: decreased 26%;14-hydroxy clarithromycin AUC: increased 34%; Cmax: increased 49%-Induction of CYP450 3A4 by efavirenz

Dose adjustment not established

Elvitegravir/cobicistat639, 623
(Genvoya, Stribild)
--Not studied; Potentially increased effectsNot studied; Potentially increased effects--

No dose adjustment necessary if patients CrCl > 60 mL/min. Reduce clarithromycin dose by 50% if CrCl is between 50-60 mL/min. Do not coadminster if CrCl < 50 mL/min.

Alternative Agents:
Azithromycin

Etravirine405
(ETR)(Intelence)
-500 mg BIDEtravirine AUC: increased 42%; Cmax: increased 46%; Cmin: increased 46%Clarithromycin AUC: decreased 37%; Cmax: decreased 34%; Cmin: decreased 53%; 14-hydroxyclarithromycin AUC: increased 21%; Cmax: increased 33%Increased etravirine effects; decreased clarithromycin effectsInduction of CYP450 3A4 by etravirine; inhibition by clarithromycin

Avoid combination if possible; consider use of azithromycin

Alternative Agents:
Azithromycin

Indinavir16, 254
(IDV)(Crixivan)
800 mg Q8H x 1 week500 mg Q12H x 1 weekIndinavir AUC: increased 29%Clarithromycin AUC: increased 53%-Inhibition of CYP450 3A4 by both drugs

No dose adjustment necessary

Indinavir359
(IDV)(Crixivan)
800 mg Q8H x 1 week500 mg Q12H x 1 weekIndinavir AUC: increased 19%; Cmax: no significant change; Cmin: increased 52%Clarithromycin AUC: increased 47%; Cmax: increased 20%; 14-hydroxyclarithromycin AUC: decreased 49%; Cmax: decreased 49%Increased indinavir effectsInhibition of CYP450 3A4 by both drugs

No dose adjustment necessary

Lopinavir/ritonavir727, 78
(LPV/r)(Kaletra)
---May increase clarithromycin levelsIncreased clarithromycin effectsInhibition of CYP450 3A4 by lopinavir/ritonavir

No dose adjustment necessary. Monitor for clarithromycin-related toxicities or consider alternative macrolide. Reduce clarithromycin dose by 50% in patients with CrCl 30– 60 mL/min. Reduce clarithromycin dose by 75% in patients with CrCl <30 mL/min.

Alternative Agents:
Azithromycin

Antiretroviral (ARV)Dose of ARVDose of ClarithromycinEffect on ARV LevelsEffect on Clarithromycin LevelsPotential Clinical EffectsMechanism of InteractionManagement
Nevirapine362, 95
(NVP)(Viramune)
200 mg QD x 2 weeks then 200 BID500 mg BIDNevirapine Cmin: no significant changeClarithromycin AUC: decreased 29%; Cmax: decreased 20%; Cmin: decreased 46%; 14-hydroxy clarithromycin AUC: increased 27%--

No dose adjustment necessary

Ritonavir360, 56
(RTV)(Norvir)
200 mg TID500 mg BIDAUC: no significant change; Cmax: increased 15%Clarithromycin AUC: increased 77%; Cmax: increased 31%; Cmin: increased 182%Increased clarithromycin effectsInhibition of CYP450 3A4 by ritonavir

No dose adjustment necessary

Saquinavir44, 75
(SQV)(Fortovase, Invirase)
1200 mg TID x 7 days500 mg BID x 7 daysSaquinavir soft gel caps AUC: increased 177%; Cmax: increased 187%; saquinavir hard gel caps AUC: increased 500%Clarithromycin AUC: increased 45%; Cmax: increased 39%; 14-hydrooxyclarithromycin AUC: decreased 24%; Cmax: decreased 34%- Inhibition of CYP450 3A4 by clarithromycin

Dose adjustment not established

Stavudine275
(d4T)(Zerit)
40 mg BID500 mg BIDStavudine AUC: no significant change; Cmax: decreased 15%; Cmin: decreased 41%---

No dose adjustment necessary

Tipranavir154
(TPV)(Aptivus)
500 mg BID with 200 mg ritonavir BID500 mg BID x 25 dosesTipranavir AUC: increased 66%; Cmax: increased 40%; Cmin: increased 100%Clarithromycin AUC: increased 19%; Cmax: no significant change; Cmin: increased 68%14-hydroxyclarithromycin AUC: decreased 97%; Cmax: decreased 97%; Cmin: decreased 95%Increased tipranavir effects; possible decreased clarithromycin effectsInhibition of CYP450 3A4 by clarithromycin; induction of CYP450 3A4 by tipranavir

No dose adjustment necessary

Zidovudine358, 81
(AZT, ZDV)(Retrovir)
-500 mg BIDZidovudine Cmax: increased 50%; AUC: no significant change---

No dose adjustment necessary

"-" indicates that there are no data available
 16:Crixivan [package insert]. Whitehouse Station, NJ: Merck & Co., Inc.; Oct 2005.
 44:Fortovase [package insert]. Basel, Switzerland: F. Hoffman-La Roche Ltd.;2003.
 56:Fiske W, Benedek IH, et al. Pharmacokinetics of efavirenz (EFV) and ritonavir (RIT) after multiple oral doses in healthy volunteers [abstract #42269]. 12th International Conference on AIDS; 1998 June 28-July 3; Geneva, Switzerland.
 60:Agenerase [package insert]. Research Triangle Park, NC: Glaxo Wellcome Inc; 2004.
 75:Invirase [package insert]. Roche Laboratories Inc, Nutley, NJ, 2007.
 78:Kaletra [package insert]. North Chicago, IL: Abbott Laboratories; Oct 2005.
 81:Retrovir [package insert]. Research Triangle Park, NC: GlaxoWellcome; Sept 2005.
 88:Rescriptor [package insert]. La Jolla, California: Agouron Pharmaceuticals, Inc; June 2001.
 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.
 275:Piscitelli SC, Kelly G, Walker RE, et al. A multiple drug interaction study of stavudine with agents for opportunistic infections in human immunodefieciency virus-infected patients. Antimicrob Agents Chemother 1999;43:647-50.
 358:Biaxin [package insert]. North Chicago, IL: Abbott Laboratories; 2003.
 359:Boruchoff SE, Sturgill MG, Grasing KW, et al. The steady-state disposition of indinavir is not altered by the concomitant administration of clarithromycin. Clin Pharmacol Ther. 2000;67:351-59.
 360:Ouellet D, Hsu A, Granneman GR, et al. Pharmacokinetic interaction between ritonavir and clarithromycin. Clin Pharmacol Ther 1998;64: 355-62.
 361:Brophy DF, Israel DS, Pastor A, et al. Pharmacokinetic interaction between amprenavir and clarithromycin in healthy male volunteers. Antimicrob Agents Chemother 2000;44: 978-84.
 362:Robinson P, Gigliotti M, Lamson M, et al. Effect of reverse transcriptase inhibitor, nevirapine, on the steady-state pharmacokinetics of clarithromycin in HIV-positive patients [abstract #374]. 6th Conference on Retroviruses and Opportunistic Infections; 1999 Jan 30-Feb 2; Chicago, Illinois.
 363:Mummaneni V, Randall D, Chabuel D, et al. Steady state pharmacokinetic (PK) interaction study of atazanavir (ATV) with clarithromycin (CLR) in healthy subjects. [abstract #H-1717]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 September 27-30; San Diego, California.
 405:Intelence [package insert]. Raritan, NJ: Tibotec Therapeutics; 2010.
 623:Stribild [package insert]. Foster City, CA: Gilead Sciences, Inc.; August 2012.
 639:DHHS. Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents. Feb 12, 2013.
 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.
 755:Evotaz [package insert]. Princeton, NJ: Bristol-Myers Squibb Company, 2017.