Anti-Infectives: Azole Antifungals and Macrolides

ANTIINFECTIVES

ANTI-INFECTIVES: AZOLE ANTIFUNGALS AND MACROLIDES

INSTIs NNRTIs PIs

xBICTEGRAVIR xELVITEGRAVIR/ x DORAVIRINE (Pifeltro, x ETRAVIRINE x EFAVIRENZ (Sustiva, Boosted with ritonavir (Biktarvy) COBICISTAT (Stribild, Delstrigo) (Intelence) Atripla) (Norvir) or cobicistat xDOLUTEGRAVIR Genvoya) x RILPIVIRINE (Edurant, x NEVIRAPINE xATAZANAVIR (Reyataz, (Tivicay, Triumeq, Complera, Odefsey, (Viramune) Evotaz) Juluca) Juluca) xDARUNAVIR (Prezista, xRALTEGRAVIR Prezcobix, Symtuza) (Isentress) xLOPINAVIR (Kaletra) AZOLE ANTIFUNGALS

xFluconazole Potential for n azole WŽƚĞŶƚŝĂůĨŽƌјEEZd/ Efavirenz (Diflucan) ĂŶĚљĂǌŽůĞ͘DŽŶŝƚŽƌ for toxicity and ĂŶƚŝĨƵŶŐĂůĞĨĨŝĐĂĐǇ͘ WŽƚĞŶƚŝĂůĨŽƌј nevirapine; monitor for ƚŽǆŝĐŝƚǇ͘

xItraconazole Potential for nĂǌŽůĞ͘ WŽƚĞŶƚŝĂůĨŽƌјEEZd/ WŽƚĞŶƚŝĂůĨŽƌљĂǌŽůĞ Potential for nĂǌŽůĞ͘ (Sporanox) Use maximum 200 mg ĂŶĚљĂǌŽůĞ͘DŽŶŝƚŽƌ Use maximum 200 mg ŝƚƌĂĐŽŶĂǌŽůĞƉĞƌĚĂǇ͘ for toxicity and ŝƚƌĂĐŽŶĂǌŽůĞƉĞƌĚĂǇ͘ ĂŶƚŝĨƵŶŐĂůĞĨĨŝĐĂĐǇ͘

xKetoconazole Potential for nĂǌŽůĞ͘ WŽƚĞŶƚŝĂůĨŽƌјEEZd/ WŽƚĞŶƚŝĂůĨŽƌљĂǌŽůĞ Potential for nĂǌŽůĞ͘ (Nizoral) Use maximum 200 mg ĂŶĚљĂǌŽůĞ͘DŽŶŝƚŽƌ Use maximum 200 mg ŬĞƚŽĐŽŶĂǌŽůĞƉĞƌĚĂǇ͘ for toxicity and ŬĞƚŽĐŽŶĂǌŽůĞƉĞƌĚĂǇ͘ ĂŶƚŝĨƵŶŐĂůĞĨĨŝĐĂĐǇ͘

xPosaconazole Potential for n azole WŽƚĞŶƚŝĂůĨŽƌјEEZd/ Efavirenz: potential for Potential for n PI (Posanol) ĂŶĚљĂǌŽůĞ͘DŽŶŝƚŽƌ љĂǌŽůĞ ĐŽŶĐĞŶƚƌĂƚŝŽŶƐ͘ for toxicity and WŽƚĞŶƚŝĂůĨŽƌј DŽŶŝƚŽƌĨŽƌƚŽǆŝĐŝƚǇ͘ ĂŶƚŝĨƵŶŐĂůĞĨĨŝĐĂĐǇ͘ nevirapine; monitor for ƚŽǆŝĐŝƚǇ͘ ANTIINFECTIVES

INSTIs NNRTIs PIs

xVoriconazole Potential for n azole WŽƚĞŶƚŝĂůĨŽƌјEEZd/ Efavirenz: potential for WŽƚĞŶƚŝĂůĨŽƌјͬљ (Vfend) ĂŶĚљĂǌŽůĞ͘DŽŶŝƚŽƌ љǀŽƌŝĐŽŶĂǌŽůĞĂŶĚј voriconazole for toxicity and ĞĨĂǀŝƌĞŶǌ͘ ĐŽŶĐĞŶƚƌĂƚŝŽŶƐ͘ ĂŶƚŝĨƵŶŐĂůĞĨĨŝĐĂĐǇ͘ Potential for љĂǌŽůĞ

MACROLIDES

xAzithromycin (Zithromax)

xClarithromycin јĐůĂƌŝƚŚƌŽŵǇĐŝŶ͘ Etravirine: Potential WŽƚĞŶƚŝĂůĨŽƌљ јĐůĂƌŝƚŚƌŽŵǇĐŝŶ͘ (Biaxin) Adjust dose with renal Potential ĨŽƌј ĐůĂƌŝƚŚƌŽŵǇĐŝŶĂŶĚј Adjust dose with renal ŝŵƉĂŝƌŵĞŶƚ͘ ĨŽƌљ rilpivirine, 14-OH metabolite and ŝŵƉĂŝƌŵĞŶƚ͘ clarithromy potential ŝŶĐƌĞĂƐĞĚƌŝƐŬŽĨƌĂƐŚ͘ ĐŝŶĂŶĚј QT 14-OH prolonga- metabolite tion x Erythromycin and increased ƌŝƐŬŽĨƌĂƐŚ͘

ANTIINFECTIVES

Mechanism of Drug Interactions, Management and Monitoring

Azole Agent Mechanism of Interaction Main Interacting ARVs Management Monitoring Fluconazole Inhibition of CYP3A4 Doravirine, rilpivirine, Use standard doses of both Antiretroviral toxicity etravirine, nevirapine, drugs. elvitegravir/cobicistat

Itraconazole, ketoconazole, Inhibition of CYP3A4 Ritonavir and cobicistat- Use maximum 200 mg Azole toxicity posaconazole (antiretrovirals) boosted PIs, ketoconazole or itraconazole elvitegravir/cobicistat daily

Substrate of CYP3A4, Efavirenz, etravirine, Avoid efavirenz and nevirapine Azole efficacy induction by most NNRTIs nevirapine if possible. Use etravirine with caution and consider increasing azole dose if necessary. Voriconazole Induction of CYP2C19 by Ritonavir-boosted PIs, Ritonavir-boosted PIs: avoid Voriconazole efficacy. some antiretrovirals; efavirenz coadministration. voriconazole also inhibits Efavirenz: increase CYP3A4. voriconazole to 400 mg q12hours and decrease efavirenz to 300 mg daily if therapy lasts more than few days. Inhibition of CYP2C19 Etravirine Etravirine toxicity

Inhibition of CYP3A4 Cobicistat-boosted PIs and Voriconazole toxicity (antiretrovirals and elvitegravir/cobicistat voriconazole)

Azithromycin Substrate of CYP3A4 (minor) Ritonavir- and cobicistat- Use standard doses of both Monitor for QT interval boosted PIs and drugs prolongation in patients elvitegravir/cobicistat with other pre-existing risk factors ANTIINFECTIVES

Azole Agent Mechanism of Interaction Main Interacting ARVs Management Monitoring FluconazoleClarithromycin Inhibition of CYP3A4 Elvitegravir/cobicistat Doravirine, rilpivirine, and Atazanavir:Use standard reduce doses of both AntiretroviralMonitor patients toxicity for signs of (ritonavir, cobicistat) boosted protease clarithromycin dose by 50% to clarithromycin toxicity inhibitors avoid QTc prolongation and including QT interval Protease inhibitors inhibit consider alternate agent for prolongation the metabolism of non-MAC infections. clarithromycin via CYP3A4 and increase concentrations Elvitegravir/cobicistat: of clarithromycin. This may Reduce dose of clarithromycin lead to a decrease in CLA-14 by 50% if CrCl is between 50- OH metabolite, reducing 60mL/min. Do not administer antibacterial activity versus clarithromycin if CrCl gram-negative organisms. <50mL/min.

Darunavir and lopinavir: reduce clarithromycin dose by 50% if CrCl 30-60mL/min; by 75% if CrCl <30mL/min. Induction of CYP3A4 Efavirenz, etravirine, May wish to consider switching Clarithromycin efficacy and resulting in decreased nevirapine to azithromycin, particularly if potential rash clarithromycin and increased treating MAC infection or CLA-14 OH metabolite, consider non-interaction NNRTI which has reduced activity such as doravirine. against Mycobacterium avium complex (MAC) Clarithromycin, Inhibition of CYP3A4 Rilpivirine Use with caution. Monitor for QT interval erythromycin (clarithromycin, prolongation in patients erythromycin) with other pre-existing risk factors

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.

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