Dosage Adjustments for ARV-ARV Drug Interactions

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October 2012

Susa Coffey, MD, University of California San Francisco
Ian McNicholl, PharmD, BCPS, University of California San Francisco

Many antiretroviral medications used to treat HIV infection, particularly certain protease inhibitors and nonnucleoside reverse transcriptase inhibitors, interact with other antiretroviral agents. These interactions are usually due to effects on hepatic drug metabolism and can cause clinically significant alterations in serum drug concentrations. Certain antiretroviral agents require dosage adjustment (or pharmacokinetic enhancement) when coadministered, and some combinations are contraindicated. This table shows evidence-based adult dosage adjustments for interacting antiretroviral medications. Not all are approved by the U.S. Food and Drug Administration.

For further information, see the Database of Antiretroviral Drug Interactions. For information about pharmacokinetic enhancement ("boosting") of protease inhibitors by ritonavir, see Dosing for Ritonavir-Boosted Protease Inhibitors.

Drug	Coadministered Drug	Dosage Adjustment
Abbreviations: ARV = antiretroviral; BID = 2 times daily; LFTs = liver function tests; PI = protease inhibitor; Q8H = every 8 hours; QD = once daily; TID = 3 times daily
Atazanavir	Efavirenz	Treatment-naive patients: Atazanavir 400 mg QD + ritonavir 100 mg QD; efavirenz 600 mg QD Treatment-experienced patients: Not recommended
	Etravirine	Do not coadminister
	Nevirapine	Do not coadminister
	Maraviroc	Atazanavir 300 mg QD + ritonavir 100 mg QD; maraviroc 150 mg BID OR Atazanavir 400 mg QD; maraviroc 150 mg BID
	Saquinavir	Dosage adjustment not established; consider atazanavir 300 mg QD + ritonavir 100 mg QD; saquinavir 1,600-2,000 mg QD
	Tenofovir	Atazanavir 300 mg QD + ritonavir 100 mg QD; tenofovir 300 mg QD (atazanavir 400 mg QD + ritonavir 100 mg QD if used concurrently with tenofovir and an H2 receptor antagonist)
	Tipranavir	Not recommended
Darunavir	Etravirine	Darunavir 600 mg BID + ritonavir 100 mg BID; etravirine 200 mg BID (dosage adjustment not necessary)
Darunavir	Maraviroc	Darunavir 600 mg BID + ritonavir 100 mg BID; mariviroc 150 mg BID
Delavirdine	Indinavir	Delavirdine 400 mg TID; indinavir 600 mg Q8H
Delavirdine	Saquinavir	Delavirdine 400 mg TID; saquinavir 800 mg TID (monitor LFTs)
Didanosine	Tenofovir	For body weight ≥60 kg, didanosine 250 mg QD; tenofovir 300 mg QD For body weight <60 kg, didanosine 200 mg QD; tenofovir 300 mg QD
Efavirenz	Atazanavir	Treatment-naive patients: Atazanavir 400 mg QD + ritonavir 100 mg QD; efavirenz 600 mg QD Treatment-experienced patients: Do not coadminister.
	Fosamprenavir	Efavirenz 600 mg QD; fosamprenavir 700 mg BID + ritonavir 100 mg BID OR Efavirenz 600 mg QD; fosamprenavir 1,400 mg QD + ritonavir 300 mg QD (QD dosing of fosamprenavir is not recommended for PI-experienced patients)
	Indinavir	Efavirenz 600 mg QD; indinavir 800-1,000 mg BID + ritonavir 100-200 mg BID
	Lopinavir/ritonavir	Efavirenz 600 mg QD; lopinavir/ritonavir 500/125 mg BID
	Maraviroc	Efavirenz 600 mg QD; maraviroc 600 mg BID
	Saquinavir	Dosage adjustment of saquinavir not established; consider efavirenz 600 mg QD; saquinavir 1,000 mg BID + ritonavir 200 mg BID
	Tipranavir	Dosage adjustment not necessary
Elvitegravir/cobicistat (coformulation)	Protease inhibitors NNRTIs	Do not coadminister
Elvitegravir/cobicistat (coformulation)	Maraviroc	No data
Etravirine	Atazanavir	Do not coadminister
	Darunavir	Etravirine 200 mg BID; darunavir 600 mg BID + ritonavir 100 mg BID (dosage adjustment not necessary)
	Lopinavir/ritonavir	No dosage adjustment appears to be necessary
	Saquinavir	Dosage adjustment not established; consider etravirine 200 mg BID; saquinavir 1000 mg BID + ritonavir 100 mg BID
	All other PIs	Do not coadminister
	Maraviroc	Etravirine 200 mg BID; maraviroc 600 mg BID (if ETV is given with MVC + DRV-r or other compatible RTV-boosted PI, reduce MVC dosage to 150 mg BID)
Fosamprenavir	Efavirenz	Fosamprenavir 700 mg BID + ritonavir 100 mg BID; efavirenz 600 mg QD OR Fosamprenavir 1,400 mg QD + ritonavir 300 mg QD; efavirenz 600 mg QD (QD dosing of fosamprenavir is not recommended for PI-experienced patients)
	Etravirine	Dosage adjustment not established; do not coadminister
	Lopinavir/ritonavir	Fosamprenavir 1,400 mg BID; lopinavir/ritonavir 500/125 mg BID
	Maraviroc	Fosamprenavir 1,400 mg BID; maraviroc 150 mg BID OR Fosamprenavir 700 mg BID + ritonavir 100 mg BID; maraviroc 150 mg BID OR Fosamprenavir 1,400 mg QD + ritonavir 200 mg QD; maraviroc 150 mg BID
	Nevirapine	Dosage adjustment of fosamprenavir not established; consider fosamprenavir 700 mg BID + ritonavir 100 mg BID; nevirapine 200 mg BID OR Fosamprenavir 1,400 mg QD + ritonavir 300 mg QD; nevirapine 200 mg BID (QD dosing of fosamprenavir is not recommended for PI-experienced patients)
	Saquinavir	Dosage adjustment not established; consider fosamprenavir 700 mg BID + ritonavir 100-200 mg BID; saquinavir 1,000 mg BID
	Tipranavir	Not recommended
Indinavir	Delavirdine	Indinavir 600 mg Q8H; delavirdine 400 mg TID
	Efavirenz	Indinavir 800-1,000 mg BID + ritonavir 100-200 mg BID; efavirenz 600 mg QD
	Etravirine	Do not coadminister
	Lopinavir/ritonavir	Indinavir 600-800 mg BID; lopinavir/ritonavir 400/100 mg (2 tablets) BID
	Maraviroc	Indinavir 800 mg BID + ritonavir 100 mg BID; maraviroc 150 mg BID OR Indinavir 800 mg Q8H; maraviroc 150 mg BID
	Nelfinavir	Indinavir 1,200 mg BID; nelfinavir 1,250 mg BID
	Nevirapine	Consider indinavir 800-1,000 mg BID + ritonavir 100-200 mg BID; nevirapine 200 mg BID
	Tipranavir	Not recommended
Lopinavir/ritonavir	Efavirenz	Lopinavir/ritonavir 500/125 mg BID (for ARV-naive patients) or 600/150 BID Lopinavir/ritonavir should not be given QD in patients taking efavirenz
	Etravirine	No dosage adjustment appears to be necessary
	Fosamprenavir	Lopinavir/ritonavir 500/125 mg BID; fosamprenavir 1,400 mg BID
	Indinavir	Lopinavir/ritonavir 400/100 mg BID; indinavir 600-800 mg BID
	Maraviroc	Lopinavir/ritonavir 400/100 mg BID; maraviroc 150 mg BID
	Nevirapine	Lopinavir/ritonavir 500/125 mg BID; nevirapine 200 mg BID Lopinavir/ritonavir should not be given QD in patients taking nevirapine
	Rilpivirine	Dosage adjustment not necessary
	Saquinavir	Lopinavir/ritonavir 400/100 mg BID; saquinavir 1,000 mg BID
	Tipranavir	Not recommended
Maraviroc	Amprenavir Atazanavir Darunavir Fosamprenavir Indinavir Lopinavir/ritonavir Saquinavir	Maraviroc 150 mg BID; PI at usual dosage
	Efavirenz Etravirine (if used without PIs listed above or other strong CYP3A inhibitor)	Maraviroc 600 mg BID, efavirenz 600 mg QD Maraviroc 600 mg BID, etravirine 200 mg BID
	Nevirapine	Maraviroc 300 mg BID (dosage adjustment not necessary); nevirapine 200 mg BID
	Rilpivirine	No data
	Tipranavir	Maraviroc 300 mg BID (dosage adjustment not necessary); tipranavir 500 mg BID + ritonavir 200 mg BID
Nelfinavir	Indinavir	Nelfinavir 1,250 mg BID; indinavir 1,200 mg BID
	Etravirine	Do not coadminister
	Maraviroc	Nelfinavir 1,250 mg BID; maraviroc 150 mg BID
Nevirapine	Atazanavir	Do not coadminister
	Fosamprenavir	Dosage adjustment of fosamprenavir not established; consider nevirapine 200 mg BID; fosamprenavir 700 mg BID + ritonavir 100 mg BID OR Nevirapine 200 mg BID; fosamprenavir 1,400 mg QD + ritonavir 300 mg QD (QD dosing of fosamprenavir is not recommended for PI-experienced patients)
	Indinavir	Consider nevirapine 200 mg BID; indinavir 800-1,000 mg BID + ritonavir 100-200 mg BID
	Lopinavir/ritonavir	Nevirapine 200 mg BID; lopinavir/ritonavir 500/125 mg BID
	Maraviroc	Nevirapine 200 mg BID; maraviroc 300 mg BID (dosage adjustment not necessary)
	Saquinavir	Dosage adjustment of saquinavir not established; consider nevirapine 200 mg BID; saquinavir 400 mg BID + ritonavir 400 mg BID
	Tipranavir	Dosage adjustment not established
Rilpivirine	Protease inhibitors	Dosage adjustment does not appear to be necessary
	Maraviroc	No data
	Elvitegravir/cobicistat	No data
Saquinavir	Atazanavir	Dosage adjustment not established; consider saquinavir 1,600-2,000 mg QD + atazanavir 300 mg QD + ritonavir 100 mg QD
	Delavirdine	Saquinavir 800 mg TID; delavirdine 400 mg TID (monitor LFTs)
	Efavirenz	Dosage adjustment of saquinavir not established; consider saquinavir 1,000 mg BID + ritonavir 200 mg BID; efavirenz 600 mg QD
	Etravirine	Saquinavir 1000 mg BID + ritonavir 100 mg BID; etravirine 200 mg BID
	Fosamprenavir	Dosage adjustment not established; consider saquinavir 1,000 mg BID + ritonavir 100-200 mg BID; fosamprenavir 700 mg BID
	Lopinavir/ritonavir	Saquinavir 1,000 mg BID; lopinavir/ritonavir 400/100 mg (2 tablets) BID
	Maraviroc	Saquinavir 1,000 mg BID + ritonavir 100-200 mg BID; maraviroc 150 mg BID
	Nevirapine	Dosage adjustment of saquinavir not established; consider saquinavir 400 mg BID + ritonavir 400 mg BID; nevirapine 200 mg BID
	Tipranavir	Not recommended
Tenofovir	Atazanavir	Tenofovir 300 mg QD; atazanavir 300 mg QD + ritonavir 100 mg QD (atazanavir 400 mg QD + ritonavir 100 mg QD if used concurrently with tenofovir and an H2 receptor antagonist)
Tenofovir	Didanosine	Tenofovir 300 mg QD; didanosine 250 mg QD (for body weight ≥60 kg) Tenofovir 300 mg QD; didanosine 200 mg QD (for body weight <60 kg)
Tipranavir	Atazanavir Darunavir Fosamprenavir Lopinavir/ritonavir Saquinavir	Combination of tipranavir and other PIs is not currently recommended
	Efavirenz Nevirapine Rilpivirine	Dosage adjustment not necessary
	Etravirine	Do not coadminister
	Maraviroc	Tipranavir 500 mg BID + ritonavir 200 mg BID; maraviroc 300 mg BID (dosage adjustment not necessary)

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