Atazanavir

Atazanavir, widely known as ATZ, and also called ATV and formerly called BMS-232632, is an antiretroviral protease inhibitor (PI) used to treat HIV/AIDS. Unlike most protease inhibitors, atazanavir can be given once a day and hence has fewer effects on patient lipid profiles. Like most protease inhibitors, it is used in combination with other HIV medications. It is sold under the brand names Latazanavir®, Reyataz® and Zrivada®. It inhibits the proteolytic cleavage of the viral polyprotein precursors (Gag and Gag-Pol) so that the individual active proteins of HIV cannot be made, thus stopping the formation of mature, infectious viral particles. This and other protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.

Its IUPAC chemical name is methyl N-[(2S)-1-[[(2S,3S)-3-hydroxy-4-[[[(2S)-2-(methoxycarbonylamino)- 3,3-dimethylbutanoyl]amino]-[(4-pyridin-2-ylphenyl)methyl]amino]-1-phenylbutan-2-yl]amino]-3,3-dimethyl-1-oxobutan-2-yl]carbamate, and its chemical formula is C₃₈H₅₂N₆O₇.

Drug interactions

The absorption of indinavir is decreased by St. John's Wort, Vitamin C, antacids, such as aluminum, bismuth, calcium, magnesium, magnesium oxide and magnesium sulfide, by efavirenz, omeprazole and related compounds (esomeprazole, lansoprazole, pantoprazole and rabeprazole) and by Rifampin and its derivitive Rifabutin. The effects of indinavir are increased when taken with clarithromycine, delavirdine or ketoconazole. Saquinavir, also a protease inhibitor, may be an agonist of indinavir.

Indinavir increases the anticoagulant effect of anisindione, acenocoumarol, dicumarol, and warfarin and also increases the effect of benzodiazepine. Benzodiazepine related drugs include Alprazolam, Chlordiazepoxide, Clonazepam, Clorazepate, Diazepam, Estazolam, Flurazepam, Halazepam, Midazolam, Prazepam, Quazepam and Triazolam.

An increased risk of cardiotoxicity and arrhythmias occurs when taken with astemizole, cisapride or terfenadine. The effects and toxicity of amiodarone, atorvastatin, carbamazepine, cyclosporine, fentanyl, fusidic acid, pimozide, sildenafil, tacrolimus and Vardenafil are increased when taken with indinavir. The effect and toxicity of ergot derivatives, such as ergotamine and dihydroergotamine, and erlotinib, quinupristin, ranolazine and trazodone are also increased. An increase in extrapyramidal symptoms may occur with risperidone and increased risks of hyperbilirubinemia are associated with atazanavir use.

Amiodarone Increased risk of cardiotoxicity and arrhythmias Amitriptyline Increases the effect and toxicity of tricyclics Amoxapine Increases the effect and toxicity of tricyclics Anisindione The protease inhibitor increases the anticoagulant effect Atorvastatin Increases the effect and toxicity of the statin Bepridil Increases the effect and toxicity of bepridil Cimetidine This gastric pH modifier decreases the levels/effects of atazanavir Cisapride Increased risk of cardiotoxicity and arrhythmias Clarithromycin Increases levels of clarithromycin Clomipramine Increases the effect and toxicity of tricyclics Cyclosporine Increases the effect and toxicity of immunosuppressant Desipramine Increases the effect and toxicity of tricyclics Dicumarol The protease inhibitor increases the anticoagulant effect Dihydroergotamine Increases the effect and toxicity of ergot derivative Dihydroquinidine barbiturate Increased risk of cardiotoxicity and arrhythmias Dihydroxyaluminium This gastric pH modifier decreases the levels/effects of atazanavir Diltiazem Increases the effect and toxicity of diltiazem Doxepin Increases the effect and toxicity of tricyclics Ergotamine Increases the effect and toxicity of ergot derivative Erlotinib This CYP3A4 inhibitor increases levels/toxicity of erlotinib Famotidine This gastric pH modifier decreases the levels/effects of atazanavir Imipramine Increases the effect and toxicity of tricyclics Indinavir Increased risk of hyperbilirubinemia with this association Irinotecan Increases levels/effect of irinotecan Lidocaine Increased risk of cardiotoxicity and arrhythmias Lovastatin Increased risk of myopathy/rhabdomyolysis Methylergonovine Increases the effect and toxicity of ergot derivative Midazolam Increases the effect and toxicity of benzodiazepine Nevirapine Nevirapine decreases levels/effect of atazanavir Acenocoumarol The protease inhibitor increase the anticoagulant effect Nizatidine This gastric pH modifier decreases the levels/effects of atazanavir Nortriptyline Increases the effect and toxicity of tricyclics Pimozide The protease inhibitor increases the effect and toxicity of pimozide Protriptyline Increases the effect and toxicity of tricyclics Quinidine Increased risk of cardiotoxicity and arrhythmias Quinidine barbiturate Increased risk of cardiotoxicity and arrhythmias Ranitidine This gastric pH modifier decreases the levels/effects of atazanavir Ranolazine Increased levels of ranolazine- risk of toxicity Rifabutin Increases levels/toxicity of rifabutin Rifampin Rifampin reduces levels and efficacy of atazanavir Ritonavir Association with dose adjustment Sildenafil Increases the effect and toxicity of sildenafil Simvastatin Increased risk of myopathy/rhabdomyolysis Sirolimus Increases the effect and toxicity of immunosuppressant Sunitinib Possible increase in sunitinib levels Tacrolimus Increases the effect and toxicity of immunosuppressant Triazolam Increases the effect and toxicity of benzodiazepine Trimipramine Increases the effect and toxicity of tricyclics Warfarin The protease inhibitor increases the anticoagulant effect Sodium bicarbonate This gastric pH modifier decreases the levels/effect of atazanavir Tenofovir Tenofovir decreases the levels/effects of atazanavir

External Links

• Atazanavir - FDA approved drug information (drug label) from DailyMed (U.S. National Library of Medicine).
• Drug Bank at http://www.drugbank.ca/cgi-bin/getCard.cgi?CARD=DB01072.txt