Over-The-Counter, Complementary and Alternative Agents Vitamins and Minerals, Herbal Products, Appearance and Performance Enhancing Supplements

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OVER-THE-COUNTER, COMPLEMENTARY AND ALTERNATIVE AGENTS VITAMINS AND MINERALS, HERBAL PRODUCTS, APPEARANCE AND PERFORMANCE ENHANCING SUPPLEMENTS

INSTIs NNRTIs PIs RTI

 BICTEGRAVIR  ELVITEGRAVIR/  DORAVIRINE  EFAVIRENZ  ATAZANAVIR • TENOFOVIR • TENOFOVIR (Biktarvy) COBICISTAT (Pifeltro, (Sustiva, Atripla) (Reyataz/Norvir, ALAFENAMIDE, DISOPROXIL, TDF (Stribild, Genvoya) Delstrigo) Evotaz) TAF (Descovy, (Viread,Truvada,  DOLUTEGRAVIR  ETRAVIRINE Biktarvy, Genvoya, Atripla, Complera, (Tivicay, Triumeq,  RILPIVIRINE (Intelence)  DARUNAVIR Odefsey, Symtuza) Delstrigo, Stribild) Juluca) (Edurant, (Prezista/Norvir,  NEVIRAPINE Complera, Prezcobix,  RALTEGRAVIR (Viramune) •ABACAVIR (Kivexa, Odefsey, Juluca) Symtuza) (Isentress) Ziagen, Triumeq)  LOPINAVIR (Kaletra)

VITAMINS AND MINERALS

 Vitamin D Potential for  vitamin D  Cations such as ↓ INSTI Potential for  INSTI calcium, Raltegravir 600 mg magnesium, iron, HD tablets aluminum, zinc, including Raltegravir 400 mg supplements and OK with calcium multivitamins with high dose calcium, iron HERBAL PRODUCTS AND SUPPLEMENTS

 Echinacea Potential  Potential for  bictegravir NNRTI Dolutegravir, raltegravir INSTIs NNRTIs PIs RTI

 Garlic Potential for  INSTI Potential for  INSTI Potential for  Potential for  Potential for  PI Potential for  TAF NNRTI NNRTI

 Ginkgo biloba Potential for  Potential for  Always use boosted NNRTI NNRTI PI

 Grapefruit juice Potential for  rilpivirine

 Milk thistle  Saw palmetto

APPEARANCE AND PERFORMANCE ENHANCING SUPPLEMENTS (APES)

 Creatine Potential additive ↑ Potential additive ↑ Rilpivirine: Potential additive ↑ Tenofovir DF: Scr without Scr without potential additive ↑ Scr without Potential additive impacting renal impacting renal Scr without impacting renal nephrotoxicity function function impacting renal function (rare) function

 Testosterone (oral Potential for  Potential for  Potential for  IM, topical) testosterone testosterone testosterone INSTIs NNRTIs PIs RTI

Anabolic steroids  Oral: oxandrolone, stanozolol  IM: nandrolone

Selective androgen receptor modulators  Andarine, ostarine

Selective estrogen Potential for Potential for  Potential for  Potential for  Potential for  receptor tamoxifen to  tamoxifen, possibly NNRTI tamoxifen and tamoxifen, possibly modulators (SERMS) bictegravir  elvitegravir possibly  NNRTI  PI  Clomiphene, tamoxifen Clomiphene OK Clomiphene OK Clomiphene OK Clomiphene OK

Aromatase Potential for  Potential for ↓ Cobicistat-boosted inhibitors aromatase inhibitor aromatase inhibitor PI: Potential for   Letrozole, aromatase inhibitor anastrazole Ritonavir-boosted PI: potential for /↓ aromatase inhibitor

Mechanism of Drug Interactions, Management and Monitoring

Mechanism of Main interacting ARVs Management Monitoring Class interaction Cation-containing Chelation and All INSTIs Management recommendations In all cases, monitor for continued viral products, including decreased absorption vary according to specific INSTI: suppression. supplements and  Bictegravir: Administer multivitamins Many Multivitamins bictegravir and polyvalent including once daily and cations simultaneously with especially those food, or separate by 2 hours. designed for women  Dolutegravir: Administer with extra Calcium and dolutegravir and polyvalent iron, and those used cations simultaneously with during pregnancy, food, or take dolutegravir 2 contain enough cations hours before or 6 hours after to lead to chelation of polyvalent cations. the integrase inhibitors  Elvitegravir/c : Stagger and limit their administration by at least 2 absorption. This results hours from mineral in lowered levels of the supplements. integrase inhibitor and  Raltegravir: ONLY 400 MG BID could result in loss of dose may be used with calcium virologic suppression. carbonate; use with other polyvalent cations is not recommended. Do not use 600 mg HD tablet with any polyvalent cations. Echinacea May induce CYP3A4 Bictegravir, doravirine, Potential for decreased ARV Antiretroviral efficacy. (mild) rilpivirine concentrations, clinical significance unclear. Garlic May induce CYP3A4, All ARVs Avoid ingestion of large amounts of Antiretroviral efficacy. Pgp garlic (fresh, cooked or supplements) Ginkgo Biloba Ginkgo may induce bictegravir, unboosted Do not use unboosted atazanavir Antiretroviral efficacy. CYP3A4 atazanavir, NNRTIs, with Ginkgo.

Mechanism of Main interacting ARVs Management Monitoring Class interaction Consider elvitegravir/cobicistat, dolutegravir or raltegravir instead of bictegravir.

Avoid Ginkgo with NNRTI; switch to boosted INSTI or INSTI metabolized via UGT, or boosted PI. Grapefruit juice May inhibit CYP3A4, rilpivirine Clinical significance unclear; caution Pgp may be warranted if patient is on other drugs which inhibit CYP3A4 and/or have QT-prolonging effect Creatine Creatine is metabolized Cobicistat, ritonavir, Increases in serum creatinine Monitor renal function. to creatinine, and may dolutegravir, secondary to inhibition of renal lead to higher serum bictegravir, rilpvirine tubular transporters generally occur creatinine without soon after starting these necessarily impacting antiretrovirals and remain stable renal function. thereafter. Use of creatine Potential additive effect supplements may enhance this when combined with effect. If additional significant ARVs which inhibit renal increases in serum creatinine occur tubular secretion of after patient is stable on creatinine. antiretrovirals, explore other causes of potential nephrotoxicity. Potential additive risk Tenofovir disoproxil Some cases of renal impairment Monitor renal function. of renal toxicity. after use of creatinine have been reported. Aromatase inhibitors Anastrazole: substrate Protease inhibitors, Potential for increased or decreased Monitor for efficacy, toxicity of aromatase (anastrozole, letrozole) of CYP3A4, UGT elvitegravir/cobicistat concentrations of aromatase inhibitors. Letrozole: substrate of (inhibition of CYP3A4, inhibitors. CYP3A4, 2A6 ritonavir may induce UGT), NNRTIs (induction of CYP3A4) Selective estrogen Clomiphene: no Bictegravir, Less interaction potential with Efficacy/toxicity of tamoxifen. receptor modulators metabolism/transporter elvitegravir/cobicistat, clomiphene versus tamoxifen. Antiretroviral efficacy. effects. PIs, NNRTIs Mechanism of Main interacting ARVs Management Monitoring Class interaction Tamoxifen: substrate If using tamoxifen, consider using and inducer of CYP3A4 an unboosted integrase inhibitor with minimal CYP3A4 involvement Potential for increased such as dolutegravir or raltegravir. tamoxifen with boosted regimens or decreased tamoxifen with enzyme inducing NNRTIs. Potential for decreased ARV concentrations via CYP3A4 induction by tamoxifen.

Legend: No dose adjustment required.

Use combination with caution. Adjustment in drug dose or frequency or additional/more frequent monitoring may be required. May wish to consult with

a pharmacist knowledgeable in HIV drug interactions. Contraindicated/avoid combination.