Updates to the Database of ARV Drug Interactions

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HIV Meds Quarterly Reference Table

Spring/Summer 2010

Susa Coffey, MD, HIV InSite Medical Editor

Ian R. McNicholl, HIV InSite Pharmacy Editor

Updates to the Database of ARV Drug Interactions

The following table summarizes recent additions to the HIV InSite Database of Antiretroviral Drug Interactions. For a full description of the updates, including references to the studies from which the data were derived, go to the database, click on a specific drug name, and search for the interacting agent.

New ARV Interactions (April 2010-August 2010)
Drug One	Drug Two	Clinical Effects	Mechanisms	Management
Source: McNicholl I. HIV InSite Database of Antiretroviral Drug Interactions. University of California San Francisco: Center for HIV Information; 2010
Atazanavir	Atovaquone	Potentially compromised antimalarial activity	↑ atovaquone glucuronidation; induction of CYP450 3A4 by atazanavir/ritonavir	Dosage adjustment not established
Atazanavir	Darunavir			No dosage adjustment necessary
Atazanavir (300 mg once daily)	Posaconazole (400 mg BID)	↑ atazanavir effects	Inhibition of CYP450 3A4 by posaconazole	Dosage adjustment not established; monitor closely for adverse effects during coadministration
Atazanavir (300 mg once daily with 100 mg ritonavir once daily)	Posaconazole (400 mg BID)	↑ atazanavir effects	Inhibition of CYP450 3A4 by posaconazole	Dosage adjustment not established; monitor closely for adverse effects during coadministration
Atazanavir	Proguanil	Potentially compromised antimalarial activity	↑ atovaquone glucuronidation; induction of CYP450 3A4 by atazanavir/ritonavir	Dosage adjustment not established
Atazanavir	Raltegravir			Dosage adjustment not established
Atazanavir	Voriconazole	↓ voriconazole effects	Possible induction of CYP450 by ritonavir	Do not coadminister
Darunavir	Rosuvastatin	No change in lipid-lowering ability within 35-day study period		No dosage adjustment necessary
Darunavir	Voriconazole	↓ voriconazole effects	Possible induction of CYP450 by ritonavir	Do not coadminister
Efavirenz	Atovaquone	Potentially compromised antimalarial activity	↑ atovaquone glucuronidation; induction of CYP450 3A4 by efavirenz	Dosage adjustment not established
Efavirenz	Posaconazole	↓ posaconazole effects	Induction of UDP-glucuronosyltransferase (UGT) by efavirenz	Dosage adjustment not established
Efavirenz	Proguanil		↑ atovaquone glucuronidation; induction of CYP450 3A4 by efavirenz	Dosage adjustment not established
Efavirenz (300 mg QHS for 7 days)	Voriconazole (400 mg Q12H on days 2-7)			No dosage adjustment necessary
Efavirenz 400 mg once daily for 9 days	Voriconazole (400 mg PO Q12H on day 1, then 200 mg Q12H on days 2-8)	↑ efavirenz effects and ↓ voriconazole effects	Inhibition of CYP450 3A4 by voriconazole and induction of CYP450 3A4 by efavirenz	Do not coadminister at standard dosages; ↑ voriconazole to 400 mg Q12H and ↓ efavirenz to 300 mg QHS
Efavirenz (300 mg QHS for 7 days)	Voriconazole (300 mg Q12H on days 2-7)	↓ voriconazole effects	Induction of CYP450 3A4 by efavirenz	Do not coadminister at standard dosages; ↑ voriconazole to 400 mg Q12H and ↓ efavirenz to 300 mg QHS
Etravirine	Itraconazole	↓ itraconazole effects
Etravirine	Posaconazole
Indinavir	Itraconazole	↑ indinavir effects	Inhibition of CYP450 3A4 by itraconazole	↓ indinavir to 600 mg Q8H; do not exceed itraconazole 200 mg BID
Indinavir	Voriconazole			No dosage adjustment necessary
Lamivudine	Chlorpropamide	Potentially ↑ serum glucose concentrations		Consider alternative agents: Glyburide, glipizide, metformin
Lopinavir/ritonavir	Atovaquone	Potentially compromised antimalarial activity	↑ atovaquone glucuronidation; induction of CYP450 3A4 by lopinavir/ritonavir	Dosage adjustment not established
Lopinavir/ritonavir	Bosentan	↑ bosentan effects	Inhibition of CYP450 3A4 by lopinavir/ritonavir	Start low and titrate bosentan to effect
Lopinavir/ritonavir	Gemfibrozil	↓ gemfibrozil effects	Reduced gemfibrozil absorption owing to lopinavir/ritonavir	Potential option includes utilizing alternative antiretrovirals; unknown whether fenofibrate has same interaction as gemfibrozil
Lopinavir/ritonavir	Proguanil	Potentially compromised antimalarial activity	↑ atovaquone glucuronidation; induction of CYP450 3A4 by lopinavir/ritonavir	Dosage adjustment not established
Lopinavir/ritonavir	Rifampin	↓ lopinavir effects at lower dosages	Induction of CYP450 3A4 by rifampin	Lopinavir/ritonavir dosage of 800/200 mg Q12H appears to compensate for rifampin-induced 3A4 induction
Nevirapine	Chlorpropamide
Raltegravir	Pravastatin			No dosage adjustment necessary
Ritonavir	Posaconazole	Possibly ↑ ritonavir effects	Inhibition of CYP450 3A4 by posaconazole; potential inhibition of UGT 1A1 by atazanavir	Dosage adjustment not necessary
Ritonavir (100 mg Q12H for 9 days)	Voriconazole (400 mg Q12H)	↓ voriconazole effects	Induction of CYP450 3A4 by ritonavir	Avoid coadministration; consider use of non-ritonavir-containing antiretroviral regimens
Ritonavir (400 mg Q12H for 9 days)	Voriconazole (400 mg Q12H)	↓ voriconazole effects	Induction of CYP450 3A4 by ritonavir	Do not coadminister
Saquinavir	Itraconazole	↑ itraconazole effects; ↑ saquinavir effects	Inhibition of CYP450 3A4 by itraconazole and saquinavir and ritonavir	Consider reducing itraconazole to 100 mg BID
Saquinavir	Ketoconazole	↑ saquinavir effects	Inhibition of CYP450 3A4 by ketoconazole	Dosage adjustment not established
Saquinavir	Methadone	↓ methadone effects (eg, withdrawal)		Monitor for signs and symptoms of methadone withdrawal; some patients may need ↑ in methadone dosage
Stavudine	Chlorpropamide	Potentially ↑ serum glucose concentrations		Consider alternative agents: Glyburide, glipizide, metformin
Tenofovir	Saquinavir			No dosage adjustment necessary

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