U.S. Food and Drug Administration

Effects of Protease Inhibitors and Other Commonly Used Medications as Determined by Drug Interaction Studies -- Table IV

December 18, 1997

This article is part of TheBody.com's archive. Because it contains information that may no longer be accurate, this article should only be considered a historical document.

Dosage Adjustments should be determined by a Physician

Drug Category Drug Name	Invirase™ Roche saquinavir	Recommend	Norvir™ Abbott ritonavir	Recommend	Crixivan® Merck indinavir	Recommend	Viracept® Agouron nelfinavir	Recommend
Antifungals
Fluconazole (Diflucan)	no studies have been conducted - no data available	---	fluconazole increase ritonavir AUC by 15%	no dosage adjustment necessary	decreases indinavir AUC by 19% ?33%	no dosage adjustment necessary	---	---
Ketoconazole (Nizoral)	Ketoconazole increases saquinavir AUC and Cmax 3-fold	no dosage adjustment necessary when ketaconazole 200 mg qd and saquinavir 600 mg tid are given	no studies have been conducted - no data available	---	ketoconazole increases indinavir AUC levels by 68 ? 48%	reduce indinavir to 600 mg q8h	ketoconazole increased nelfinavir AUC levels by 35%	no dosage adjustment necessary
Antimycobacterials
Clarithromycin (Biaxin)	no studies have been conducted - no data available	---	clarithromycin AUC increases by 77% rifabutin AUC increases by 4 fold rifabutin metabolite (25-0-desacetyl) AUC increases by 35 fold	dosage adjustment to patient with renal impairment is necessary	increase indinavir AUC by 29% ? 42% and increases clarithromycin AUC by 53% ? 36%	no dosage adjustment necessary	---	---
Rifabutin (Mycobutin)	rifabutin decreases saquinavir levels by 40%	if rifabutin therapy is warranted, consider alternative drugs	---	coadministration of ritonavir and rifabutin is contraindicated	rifabutin AUC increases by 204 ? 142%	reduce rifabutin to half the standard dose	rifabutin AUC increases by 207%	reduce rifabutin to half the standard dose
Rifampin (Rifadin, others)	rifampin decreases saquinavir levels by 80%	rifampin and saquinavir should not be administered concomitantly	rifampin decreases ritonavir levels by 35%	no dosage adjustment necessary	---	rifampin and indinavir should not be administered concomitantly	rifampin decreases nelfinavir by approximately 82%	rifampin and nelfinavir should not be administered concomitantly
NNRTIs
Delavirdine	5-fold increase in saquinavir AUC	Limited safety and no efficacy data from combination; monitor ALT/AST frequently	No evidence of interaction at doses of DLV 400 to 600 mg bid and ritonavir 300 mg bid	No safety and efficacy data from this combination	increase in indinavir plasma concentrations	Dose reduction of indinavir to 600 mg tid should be considered. No safety and efficacy data from this combination	---	---
Nevirpine?	27% decrease n saquinavir AUC	No safety and efficacy data from this combination	11% decrease in ritonavir AUC(0-22 hour)	No safety data from this combination	28% decrease in indinavir AUC (0-8 hour)	Dose adjustment of indinavir 1000 mg q8h should be considered. No safety and efficacy data from this combination	---	---
Oral Contraceptives	no studies have been conducted- no data available	---	ethinyl estradiol AUC decreases by 40%	dosage increase or alternative contraceptive measures should be considered	Othro-Novum 1/35 decrease ethinyl estradiol 24 ? 17% and norethindrone by 26 ? 14%	no dosage adjustment necessary	Ovcon-35 decreases ethinyl estradiol by 47% and norethindrone by 18%	alternate or additional contraceptive measures should be used
Protease Inhibitors
Indinavir	---	---	---	---	---	---	83% increase in nelfinavir AUC and 51% increase in indinavir AUC	No safety and efficacy data from this combination
Nelfinavir	18% increase in nelfinavir AUC and 392% increase in saquinavir AUC with soft gelatin formulation of saquinavir	No dose adjustment is needed with hard gelatin formulation of saquinavir; dose adjustments unknown for soft gelatin formulation. Safety/efficacy not established	152% increase in nelfinavir AUC and very little change in ritonavir AUC	Safety/efficacy of this combination has not been established	83% increase in nelfinavir AUC and 51% increase in indinavir AUC	Safety/efficacy of this combination has not been established	---	---
Ritonavir	20-fold increase in steady state dose-normalized saquinavir concentration with ritonavir doses of 400 or 600 mg bid	Currently under study - safety/efficacy has not been established	---	---	---	---	152% increase in nelfinavir AUC and very little change in ritonavir AUC	No safety and efficacy data from this combination
Saquinavir	---	---	20-fold increase in steady state dose-normalized saquinavir concentration with ritonavir doses of 400 or 600 mg bid	Currently under study - safety/efficacy has not been established	---	---	18% increase in nelfinavir AUC and 392% increase in saquinavir AUC with soft gelatin formulation of saquinavir	No dose adjustment is needed with hard gelatin formulation of saquinavir; dose adjustments unknown for soft gelatin formulation. Safety/efficacy not established.
Other
	ritonavir markedly increase saquinavir plasma levels (see ritonavir)	safety of this interaction has not been established	desipramine (Norpramin, others) AUC increase by 145%	dosage reduction should be considered	grapefruit juice decreases indinavir levels by 26%	---	---	---
	---	---	greater than 20-fold increase in saquinavir AUC	safety of this interaction has not been established	---	---	---	---
	---	---	theophylline (Theo-Dur, others) AUC decreases by 43%	dosage increase may be required	---	---	---	---
	---	---	tobacco decreases ritonavir AUC by 18%	---	---	---	---	---

1. May 23, 1997 letter from Roxane Laboratories, Inc.

AUC - Area under the Cure is a measurement of plasma concentration levels

qd - every day

bid - twice a day

tid - three times a day

q8h - every eight hours

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This article is part of TheBody.com's archive. Because it contains information that may no longer be accurate, this article should only be considered a historical document.

This article was provided by U.S. Food and Drug Administration. It is a part of the publication Protease Inhibitors Backgrounder.

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