Interactions between Nutritional supplements/herbs and Antiretrovirals

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Database of Antiretroviral Drug Interactions

Interactions with Calcium carbonate
Antiretroviral (ARV)	Dose of ARV	Dose of Calcium carbonate	Effect on ARV Levels	Effect on Calcium carbonate Levels	Potential Clinical Effects	Mechanism of Interaction	Management
Bictegravir⁷⁵⁹ (Biktarvy)	50 mg x 1	1200 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.
Dolutegravir^{685, 641} (Tivicay)	50 mg x 1	1200 mg	Dolutegravir 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 ARV	Dose of Echinacea	Effect on ARV Levels	Effect on Echinacea Levels	Potential Clinical Effects	Mechanism of Interaction	Management
Lopinavir/ritonavir⁵²⁷ (LPV/r)(Kaletra)	400/100 mg BID x 29.5 days	500 mg TID x 28 days	No significant change	-	-	-	No dose adjustment necessary
"-" indicates that there are no data available

Interactions with Ferrous fumarate
Antiretroviral (ARV)	Dose of ARV	Dose of Ferrous fumarate	Effect on ARV Levels	Effect on Ferrous fumarate Levels	Potential Clinical Effects	Mechanism of Interaction	Management
Bictegravir⁷⁵⁹ (Biktarvy)	50 mg x 1	324 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 mg	324 mg	Dolutegravir 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 ARV	Dose of Garlic	Effect on ARV Levels	Effect on Garlic Levels	Potential Clinical Effects	Mechanism of Interaction	Management
Saquinavir^{75, 172} (SQV)(Fortovase, Invirase)	1200 mg (soft gel caps) TID with food x 4 days	Garlic capsules (3.6 mg/caplet) BID on days 5-24	Saquinavir AUC: decreased 51%; Cmax: decreased 54%; Cmin: decreased 49%After a 10 day garlic washout period, pharmacokinetic values returned to only 60-70% of baseline	Not studied	Decreased saquinavir effects	Possible 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 ARV	Dose of Ginkgo biloba	Effect on ARV Levels	Effect on Ginkgo biloba Levels	Potential Clinical Effects	Mechanism of Interaction	Management
Lopinavir/ritonavir⁶²¹ (LPV/r)(Kaletra)	400/100 mg BID	120 mg BID	No significant change	-	-	-	No dose adjustment necessary
Raltegravir⁶¹⁹ (RAL)(Isentress)	400 mg x 1	120 mg BID	No significant change	Ginkgo 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 ARV	Dose of Ginseng	Effect on ARV Levels	Effect on Ginseng Levels	Potential Clinical Effects	Mechanism of Interaction	Management
Indinavir⁴⁴⁶ (IDV)(Crixivan)	800 mg Q8H	1000 mg Q8H	No significant change	-	-	-	No dose adjustment necessary
"-" indicates that there are no data available

Interactions with Milk thistle
Antiretroviral (ARV)	Dose of ARV	Dose of Milk thistle	Effect on ARV Levels	Effect on Milk thistle Levels	Potential Clinical Effects	Mechanism of Interaction	Management
Darunavir⁶¹³ (DRV)(Prezista)	-	150 mg Q8H	Darunavir AUC: decreased 14%; Cmax: decreased 17%; Cmin: no significant change	-	-	-	No dose adjustment necessary
Indinavir³⁷⁴ (IDV)(Crixivan)	800 mg Q8H	175 mg TID x 3 weeks	Indinavir AUC: no significant change; Cmin: decreased 25%	-	-	Unknown	No dose adjustment necessary
Indinavir³⁷² (IDV)(Crixivan)	800 mg Q8H on days 1-30	450 mg TID on days 2-30	No significant change	-	-	-	No dose adjustment necessary
Indinavir³⁷³ (IDV)(Crixivan)	800 mg TID x 4 doses on days 1, 2 and days 16 and 17	160 mg TID on days 3-17	No significant effect	Not studied	-	-	No dose adjustment necessary
"-" indicates that there are no data available

Interactions with Multiple vitamin
Antiretroviral (ARV)	Dose of ARV	Dose of Multiple vitamin	Effect on ARV Levels	Effect on Multiple vitamin Levels	Potential Clinical Effects	Mechanism of Interaction	Management
Dolutegravir⁶⁴¹ (Tivicay)	50 mg x 1	One-A-Day given simultaneously with dolutegravir	Dolutegravir 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 ARV	Dose of St. John's Wort	Effect on ARV Levels	Effect on St. John's Wort Levels	Potential Clinical Effects	Mechanism of Interaction	Management
Amprenavir⁶⁰ (APV)(Agenerase)	-	-	Not studied; may decrease amprenavir levels	Not studied	May decrease amprenavir effects	Induction of CYP450 3A4 by St. John's Wort	Do not coadminister
Atazanavir^{(ATV)(Reyataz)}	-	-	Not studied; may decrease atazanavir levels	-	Decreased atazanavir effects	Induction of CYP450 3A4 by St. John's Wort	Do not coadminister
Darunavir¹⁶¹ (DRV)(Prezista)	-	-	Not studied; may decrease darunavir/ritonavir levels	-	Decreased darunavir/ritonavir effects	Induction 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 ARV	Dose of St. John's Wort	Effect on ARV Levels	Effect on St. John's Wort Levels	Potential Clinical Effects	Mechanism of Interaction	Management
Efavirenz⁹⁰ (EFV)(Sustiva)	-	-	Not studied, may decrease efavirenz levels	-	Decreased efavirenz effects	Induction 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 efficacy	Induction of CYP450 3A4 by St. John's Wort	Do not coadminister
Indinavir¹⁷³ (IDV)(Crixivan)	800 mg Q8H	300 mg TID (with meals)	Indinavir AUC: decrease 57+/-19%	Not studied	May decrease effect of indinavir; indinavir resistance	Possible 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 effects	Induction of CYP450 3A4 by St. John's Wort	Do not coadminister
Nelfinavir^{173, 24} (NFV)(Viracept)	-	-	May decrease nelfinavir levels	-	Decreased nelfinavir effects	Induction of CYP450 3A4 by St. John's wort	Do not coadminister
Nevirapine¹⁷⁴ (NVP)(Viramune)	200 mg BID	-	Clearance: increased 35%	-	Decreased nevirapine effects	Induction of CYP450 3A4 by St. John's Wort	Do not coadminister
Ritonavir⁵⁵ (RTV)(Norvir)	-	-	Not studied; may decrease ritonavir levels	-	Decreased ritonavir effects	Induction of CYP450 3A4 by St. John's Wort	Do not coadminister
Saquinavir²⁵⁴ (SQV)(Fortovase, Invirase)	-	-	May decrease saquinavir levels	-	Decreased saquinavir effects	Possible 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 ARV	Dose of Vitamin C	Effect on ARV Levels	Effect on Vitamin C Levels	Potential Clinical Effects	Mechanism of Interaction	Management
Indinavir³⁸³ (IDV)(Crixivan)	800 mg Q8H x 4 doses	1 g QD x 7 days	Indinavir 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

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