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Database of Antiretroviral Drug Interactions

Interactions between Nutritional supplements/herbs and Antiretrovirals

Interactions with Calcium carbonate
Antiretroviral (ARV)Dose of ARVDose of Calcium carbonateEffect on ARV LevelsEffect on Calcium carbonate LevelsPotential Clinical EffectsMechanism of InteractionManagement
Bictegravir759
(Biktarvy)
50 mg x 11200 mg x 1 If administered simultaneously in the fasted state Cmax decreased 42%; AUC decreased 33%. If administered simultaneously in the fed state Cmax decreased 10%; AUC increased 3%. Not studied Potential loss of antiviral efficacy-

Bictegravir should be administered simultaenously with calcium carbonate supplements, with food.

Dolutegravir685, 641
(Tivicay)
50 mg x 11200 mgDolutegravir AUC decreased ~39% if taken together, fasting conditions. No significant change in dolutegravir AUC if taken 2 hours before calcium carbonate or if taken simultaneously with food.-Potential decreased dolutegravir effectiveness if taken in fasted state-

Administer dolutegravir 2 hours before or 6 hours after calcium-containing supplements. Alternatively, administer dolutegravir simulatenously with calcium supplements and with food.

"-" indicates that there are no data available
Interactions with Echinacea
Antiretroviral (ARV)Dose of ARVDose of EchinaceaEffect on ARV LevelsEffect on Echinacea LevelsPotential Clinical EffectsMechanism of InteractionManagement
Lopinavir/ritonavir527
(LPV/r)(Kaletra)
400/100 mg BID x 29.5 days500 mg TID x 28 daysNo significant change---

No dose adjustment necessary

"-" indicates that there are no data available
Interactions with Ferrous fumarate
Antiretroviral (ARV)Dose of ARVDose of Ferrous fumarateEffect on ARV LevelsEffect on Ferrous fumarate LevelsPotential Clinical EffectsMechanism of InteractionManagement
Bictegravir759
(Biktarvy)
50 mg x 1324 mg x 1 If administered simultaneously in the fasted state Cmax decreased 71%; AUC decreased 63%. If administered simultaneously in the fed state Cmax decreased 25%; AUC decreased 16%. Not studied Potential loss of antiviral efficacy-

Bictegravir should be administered simultaenously with iron supplements, with food. Monitor for virologic efficacy.

Dolutegravir687
(Tivicay)
50 mg324 mgDolutegravir AUC decreased 54% when administered simultaneously with ferrous fumarate, fasting conditions. No significant change in dolutegravir AUC if given simultaneously with ferrous fumarate, with food or if given 2 hours after ferrous fumarate.-Potentially decreased dolutegravir effectiveness if given with iron.Chelation of dolutegravir by divalent cations

Administer dolutegravir 2 hours before or 6 hours after medicines with divalent cations (Ca++, Fe++). Alternatively, dolutegravir can be taken simultaneously with iron supplements, with food.

"-" indicates that there are no data available
Interactions with Garlic
Antiretroviral (ARV)Dose of ARVDose of GarlicEffect on ARV LevelsEffect on Garlic LevelsPotential Clinical EffectsMechanism of InteractionManagement
Saquinavir75, 172
(SQV)(Fortovase, Invirase)
1200 mg (soft gel caps) TID with food x 4 daysGarlic capsules (3.6 mg/caplet) BID on days 5-24Saquinavir AUC: decreased 51%; Cmax: decreased 54%; Cmin: decreased 49%After a 10 day garlic washout period, pharmacokinetic values returned to only 60-70% of baselineNot studiedDecreased saquinavir effectsPossible induction of gut mucosal CYP450 3A4 by garlic; P-glycoprotein effects are also possible

Avoid garlic supplements when saquinavir is used either boosted or unboosted.

"-" indicates that there are no data available
Interactions with Ginkgo biloba
Antiretroviral (ARV)Dose of ARVDose of Ginkgo bilobaEffect on ARV LevelsEffect on Ginkgo biloba LevelsPotential Clinical EffectsMechanism of InteractionManagement
Lopinavir/ritonavir621
(LPV/r)(Kaletra)
400/100 mg BID120 mg BIDNo significant change---

No dose adjustment necessary

Raltegravir619
(RAL)(Isentress)
400 mg x 1120 mg BIDNo significant changeGinkgo biloba AUC: increased 21%; Cmax: increased 44%-Potential increase in raltegravir bioavailability

No dose adjustment necessary

"-" indicates that there are no data available
Interactions with Ginseng
Antiretroviral (ARV)Dose of ARVDose of GinsengEffect on ARV LevelsEffect on Ginseng LevelsPotential Clinical EffectsMechanism of InteractionManagement
Indinavir446
(IDV)(Crixivan)
800 mg Q8H1000 mg Q8HNo significant change---

No dose adjustment necessary

"-" indicates that there are no data available
Interactions with Milk thistle
Antiretroviral (ARV)Dose of ARVDose of Milk thistleEffect on ARV LevelsEffect on Milk thistle LevelsPotential Clinical EffectsMechanism of InteractionManagement
Darunavir613
(DRV)(Prezista)
-150 mg Q8HDarunavir AUC: decreased 14%; Cmax: decreased 17%; Cmin: no significant change---

No dose adjustment necessary

Indinavir374
(IDV)(Crixivan)
800 mg Q8H175 mg TID x 3 weeksIndinavir AUC: no significant change; Cmin: decreased 25%--Unknown

No dose adjustment necessary

Indinavir372
(IDV)(Crixivan)
800 mg Q8H on days 1-30450 mg TID on days 2-30No significant change---

No dose adjustment necessary

Indinavir373
(IDV)(Crixivan)
800 mg TID x 4 doses on days 1, 2 and days 16 and 17160 mg TID on days 3-17No significant effectNot studied--

No dose adjustment necessary

"-" indicates that there are no data available
Interactions with Multiple vitamin
Antiretroviral (ARV)Dose of ARVDose of Multiple vitaminEffect on ARV LevelsEffect on Multiple vitamin LevelsPotential Clinical EffectsMechanism of InteractionManagement
Dolutegravir641
(Tivicay)
50 mg x 1One-A-Day given simultaneously with dolutegravirDolutegravir AUC: decreased 33%; Cmin: decreased 32%-Potentially decreased dolutegravir effectiveness-

Administer dolutegravir 2 hours before or 6 hours after multivitamins.

"-" indicates that there are no data available
Interactions with St. John's Wort
Antiretroviral (ARV)Dose of ARVDose of St. John's WortEffect on ARV LevelsEffect on St. John's Wort LevelsPotential Clinical EffectsMechanism of InteractionManagement
Amprenavir60
(APV)(Agenerase)
- - Not studied; may decrease amprenavir levelsNot studiedMay decrease amprenavir effectsInduction of CYP450 3A4 by St. John's Wort

Do not coadminister

Atazanavir
(ATV)(Reyataz)
--Not studied; may decrease atazanavir levels-Decreased atazanavir effectsInduction of CYP450 3A4 by St. John's Wort

Do not coadminister

Darunavir161
(DRV)(Prezista)
--Not studied; may decrease darunavir/ritonavir levels-Decreased darunavir/ritonavir effectsInduction of CYP450 3A4 by St. John's Wort

Do not coadminister

Dolutegravir691
(Tivicay)
--Not studied; may decrease dolutegravir levels-Potentially decreased dolutegravir effectiveness Induction of CYP450 3A4 by St. John's Wort

Contraindicated - do not coadminister

Doravirine761
(Pifeltro, Delstrigo)
---- Potential loss of antiviral efficacy-

Contraindicated. Use alternative agents. If discontinuing St. John's Wort, a minimum 4 week cessation period is recommended prior to initiating doravirine.

Antiretroviral (ARV)Dose of ARVDose of St. John's WortEffect on ARV LevelsEffect on St. John's Wort LevelsPotential Clinical EffectsMechanism of InteractionManagement
Efavirenz90
(EFV)(Sustiva)
- - Not studied, may decrease efavirenz levels- Decreased efavirenz effectsInduction of CYP450 3A4 by St. John's Wort

Do not coadminister

Elvitegravir/cobicistat623
(Genvoya, Stribild)
----Potentially decreased elvitegravir and cobicistat effects Induction of CYP450 3A4 by St. John's Wort

Do not coadminister

Elvitegravir/ritonavir-boosted protease inhibitor691
--Expected decrease in elvitegravir, cobicistat, and protease inhibitor levels-Potentially decreased antiretroviral effects and efficacyInduction of CYP450 3A4 by St. John's Wort

Do not coadminister

Indinavir173
(IDV)(Crixivan)
800 mg Q8H300 mg TID (with meals)Indinavir AUC: decrease 57+/-19%Not studiedMay decrease effect of indinavir; indinavir resistancePossible induction of CYP450 3A4 by St. John's wort

Do not coadminister; active ingredient/quantity of hypericum varies between products and among individual tablets or capsules within the same product

Lopinavir/ritonavir78
(LPV/r)(Kaletra)
- - Not studied; may decrease lopinavir/ritonavir levels- Decreased lopinavir/ritonavir effectsInduction of CYP450 3A4 by St. John's Wort

Do not coadminister

Nelfinavir173, 24
(NFV)(Viracept)
- - May decrease nelfinavir levels- Decreased nelfinavir effectsInduction of CYP450 3A4 by St. John's wort

Do not coadminister

Nevirapine174
(NVP)(Viramune)
200 mg BID- Clearance: increased 35%- Decreased nevirapine effectsInduction of CYP450 3A4 by St. John's Wort

Do not coadminister

Ritonavir55
(RTV)(Norvir)
- - Not studied; may decrease ritonavir levels- Decreased ritonavir effectsInduction of CYP450 3A4 by St. John's Wort

Do not coadminister

Saquinavir254
(SQV)(Fortovase, Invirase)
--May decrease saquinavir levels-Decreased saquinavir effectsPossible induction of CYP450 3A4 by St. John's Wort

Do not coadminister

"-" indicates that there are no data available
Interactions with Vitamin C
Antiretroviral (ARV)Dose of ARVDose of Vitamin CEffect on ARV LevelsEffect on Vitamin C LevelsPotential Clinical EffectsMechanism of InteractionManagement
Indinavir383
(IDV)(Crixivan)
800 mg Q8H x 4 doses1 g QD x 7 daysIndinavir AUC: no significant change; Cmin: decreased 32%; Cmax: decreased 20%---

No dose adjustment necessary

"-" indicates that there are no data available
 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.
 75:Invirase [package insert]. Roche Laboratories Inc, Nutley, NJ, 2007.
 78:Kaletra [package insert]. North Chicago, IL: Abbott Laboratories; Oct 2005.
 90:Sustiva [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; Dec 2011.
 161:Prezista [package insert]. Raritan, NJ: Tibotec Therapeutics Inc.; April 2010.
 172:Piscitelli SC, Burstein AH, Welden N, et al. Effect of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis 2002;34:234-8.
 173:Piscitelli SC, Burstein AH, Chaitt D, et al. Indinavir concentrations and St. John's wort. [letter] Lancet. 2000;355:547-548.
 174:de Maat MMR, Mathot RAA, Hoetelmans RMW, et al. A population pharmacokinetic model of nevirapine reveals drug interaction with St. John's wort in a cohort of HIV-1-infected patients [abstract #1.2]. 2nd International Workshop on Clinical Pharmacology of HIV Therapy; 2001 April 2-4; Noordwijk, the Netherlands.
 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.
 372:Mills EJ, Wilson K, Clarke MJ, et al. Milk thistle and indinavir: a randomized controlled pharmacokinetics study [abstract TuPeB4611]. XV International AIDS Conference; 2004 July 11-16; Bangkok, Thailand.
 373:DiCenzo R, Shelton M, Jordan K, et al. Coadministration of milk thistle and indinavir in healthy subjects. Pharmacotherapy 2003; 23: 866-70.
 374:Piscitelli SC, Formentini E, Burstein AH, et al. Effect of milk thistle on the pharmacokinetics of indinavir in healthy volunteers. Pharmacotherapy 2002;22:551-56.
 383:Slain D, Amsden JR, Khakoo RA, et al. Effect of high-dose vitamin C (Vit C) on the steady-state pharmacokinetics (PK) of the protease inhibitor (PI) indinavir (IDV) in healthy volunteers [abstract #A-1610]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2003 September 14-17; Chicago, Illinois.
 446:Andrade AS, Hendrix C, Parsons TL, et al. Pharmacokinetic and metabolic effects of Americian ginseng (Panax quinquefolius) in healthy volunteers receiving the HIV protease inhibitor indinavir. BMC Complement Altern Med 2008; 8: 50.
 527:Penzak SR, Robertson SM, Hunt JD, et al. Echinacea purpurea significantly induces cytochrome P450 3A activity but does not alter lopinavir-ritonavir exposure in healthy subjects. Pharmacother 2010; 30: 797-805.
 613:Molto J, Valle M, Miranda C, et al. Effect of milk thistle on the pharmacokinetics of darunavir/ritonavir in HIV-infected patients [abstract P-O4]. Rev Antiviral Ther Infect Dis 2012; 3: 7.
 619:Blonk M, Colbers A, Poirters A, Schouwenberg B, Burger D. Effect of ginkgo biloba on the pharmacokinetics of raltegravir in healthy volunteers. Antimicrob Agents Chemother 2012; July 16. [Epub ahead of print].
 621:Robertson SM, Davey RT, Voell J, et al. Effect of Ginkgo biloba extract on lopinavir, midazolam and fexofenadine pharmacokinetics in healthy subjects. Curr Med Res Opin 2008; 24: 591-99.
 623:Stribild [package insert]. Foster City, CA: Gilead Sciences, Inc.; August 2012.
 641:Tivicay [package insert]. Research Triangle Park, NC: Viiv Healthcare; Sept 2013.
 685:Song I, Borland J, Arya N, Wynne B, Piscitelli S. The effect of calcium and iron supplements on the pharmacokinetics of Dolutegravir in healthy subjects. 15th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy. May 19-21, 2014. Washington, DC. Abstract P_13.
 687:Song, I., Borland, J., Arya, N., Wynne, B. and Piscitelli, S. (2015), Pharmacokinetics of dolutegravir when administered with mineral supplements in healthy adult subjects. Journal of Clinical Pharma, 55: 490–496
 691:Tivicay [package insert]. Research Triangle Park, NC: Viiv Healthcare; August 2015
 759:Biktarvy [package insert]. Foster City, CA: Gilead Sciences, 2018
 761:Pifeltro [package insert]. Whitehouse Stateion, NJ: Merck & Co. Inc., 2018