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©2013 UpToDate ® Print Email Antiretroviral drugs: Potential for interaction with anticancer agents Antiretroviral drugs Route of elimination Effect on CYP450/transporters Effect of cancer drugs on ARV as a substrate Alteration to cancer drugs due to enzyme or transporter induction or inhibition Nucleoside reverse-transcriptase inhibitors (NRTIs) Abacavir [1-4] Renal excretion, ALDH, UGT*, ABCB1, ABCG2 Inhibitor: ABCB1, ABCC1, ABCC2, ABCC3, ABCG2 2 2 Didanosine [4-5] Renal excretion, purine nucleoside phosphorylase, ABCC4 None known 2 1 Emtricitabine [6-8] Renal excretion, UGT*, ABCC1 Inducer: ABCC5 Inhibitor: ABCC1 2 2 Lamivudine [4,9-11] Renal excretion, ABCB1, ABCC1, ABCC2, ABCC3, ABCC4, ABCG2, SLC22A1, SLC22A2, SLC22A3 Inhibitor: ABCC1, ABCC2, ABCC3 2 2 Stavudine [4,12] Renal excretion, ABCC4 Inducer: ABCB1 2 2 Zidovudine [4,10,13-15] CYP2A6, CYP2C9, CYP2E1, CYP3A4, UGT2B7, ABCB1, ABCC4, ABCC5, ABCG2, SLC22A6, SLC22A7,SLC22A8, SLC22A11, SLC28A1, SLC28A3 Inducer: ABCC4, ABCC5 Inhibitor: ABCG2 2 2 Nucleotide reverse-transcriptase inhibitors (NtRTIs) Tenofovir [4,10,16-17] Renal excretion, ABCC4, ABCC10, SLC22A6, SLC22A8 Inducer: ABCB1 Inhibitor: CYP1A2 2 2 Non-nucleoside reverse-transcriptase inhibitor (NNRTIs) Delavirdine [4,18-19] CYP2D6, CYP3A4 Inducer: ABCB1 Inhibitor: CYP2C9, CYP2C19, CYP2D6, CYP3A4, ABCB1, ABCC1, ABCC2, ABCC3, ABCG2 2 2 (inhibitor) Efavirenz [4,20-26] CYP2B6, CYP3A, UGT2B7 Inducer: CYP2B6, CYP3A4, ABCC1, ABCC6 Inhibitor: CYP2C9, CYP2C19, CYP3A4, UGT1A4, UGT1A9, ABCB1, ABCB11, ABCC1, ABCC2, ABCC3, ABCG2 2 3 (inducer) Etravirine [4,27-28] CYP2C9, CYP2C19, CYP3A4, UGT1A3, UGT1A8 Inducer: CYP3A4 Inhibitor: CYP2C9, CYP2C19, ABCB1 2 3 (inducer) Nevirapine [4,24,29,30] CYP2B6, CYP2D6, CYP3A4, UGT* Iinducer: CYP2B6, CYP3A4, ABCB1 Inhibitor: ABCB1, ABCC1, ABCC3, ABCG2 2 3 (inducer) Rilpivirine [31] CYP3A4 None 3 1 Ritonavir or ritonavir-boosted HIV-1 protease inhibitors (PI) Amprenavir [4,32-37] CYP2C9, CYP2D6, CYP3A4, UGT*, ABCB1 Inducer: CYP3A4, ABCB1 Inhibitor: CYP3A4, ABCB1, ABCC1, ABCG2, SLCO1B1, SLCO1B3 2 4 (inhibitor) • Darunavir [4,38-40] CYP3A4, ABCB1, ABCC2, SLCO1A2, SLCO1B1 Inducer: ABCB1, SLCO2B1 Inhibitor: CYP2D6, CYP3A4, ABCB1, ABCG2, SLCO1B1, SLCO1B3, SLCO2B1 2 4 (inhibitor) • Fosamprenavir (prodrug) [32-33,41] Hydrolyzed to amprenavir See amprenavir 2 4 (inhibitor) • Indinavir [4,32,36,40,42-47] CYP3A4, UGT*, ABCB1, ABCC2 Inhibitor: CYP2D6, CYP3A4, UGT1A1, ABCB1, SLCO1A2, SLCO1B1, SLCO1B3 2 4 (inhibitor) • Lopinavir [4,40,47-51]

Inducer: ABCB1, SLCO2B1 Inhibitor: CYP2D6, CYP3A4, ABCB1, ABCG2, SLCO1B1, SLCO1B3, SLCO2B1 2 4 (inhibitor) • Fosamprenavir (prodrug) [32-33,41] Hydrolyzed to amprenavir See amprenavir 2 4 (inhibitor) • Indinavir [4,32,36,40,42-47] CYP3A4, UGT*, ABCB1, ABCC2 Inhibitor: CYP2D6, CYP3A4, UGT1A1, ABCB1, SLCO1A2, SLCO1B1, SLCO1B3 2 4 (inhibitor) • Lopinavir [4,40,47-51] CYP3A4, ABCB1, ABCC1, ABCC2, SLCO1A2, SLCO1B1 Inducer: CYP1A2, CYP2C9, CYP2C19 Inhibitor: CYP3A4, UGT1A1, ABCB1, ABCG2, SLCO1B1, SLCO1B3, SLCO2B1 2 4 (inhibitor) • Ritonavir [4,24-25,32,36,40,42,44-45,52-56] CYP1A2, CYP2B6, CYP2D6, CYP3A4, ABCB1, ABCC2 Inducer: CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP3A4, UGT*, ABCB1, ABCC1 Inhibitor: CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A, ABCB1, ABCB11, ABCG2, SLCO1A2, SLCO1B1, SLCO1B3, SLCO2B1 2 4 (inhibitor or inducer) Saquinavir [4,25,32,36,39,40,42,44-45,47,50] CYP2D6, CYP3A4, ABCB1, ABCC2, SLCO1A2, SLCO1B1, SLCO1B3 Inducer: ABCB1, ABCC1, ABCC2, ABCC4, ABCC5, ABCG2 Inhibitor: CYP2C9, CYP2C19, CYP2D6, CYP3A4, UGT1A1, ABCB1, ABCB11, ABCC2, ABCG2, SLCO1B1, SLCO1B3, SLCO2B1 2 4 (inhibitor) • Tipranavir [4,57-59] CYP3A4, UGT*, ABCB1 Inducer: CYP3A4, ABCB1 Inhibitor: CYP1A2, CYP2C9, CYP2C19, CYP2D6, ABCG2 2 4 (inhibitor or inducer) • Non-ritonavir boosted HIV-1 protease inhibitors (PI) Atazanavir [4,40,47,50,60-63] CYP3A4, ABCB1, ABCC1, ABCG2 Inducer: ABCB1, ABCC1 Inhibitor: CYP2C8, CYP3A4, UGT1A1, ABCB1, ABCC1, ABCC2, ABCG2, SLCO1B1, SLCO1B3, SLCO2B1 2 2 (inhibitor) Nelfinavir [4,32,35,42,44,64-66] CYP2C9, CYP2C19, CYP2D6, CYP3A4, ABCB1 Inducer: CYP2C9, CYP3A4, UGT*, ABCB1, ABCC2 Inhibitor: CYP2D6, CYP3A4, ABCB1, ABCG2 2 2 (inhibitor or inducer) Integrase strand transfer inhibitors Raltegravir [4,67-69] UGT1A1, ABCB1, SLC15A1, SLC22A6 Inducer: ABCB1 2 2 Fusion inhibitors Enfuvirtide [4,70] Catabolism None known 1 1 Entry inhibitors (chemokine receptor antagonists) Maraviroc [4,68,71-75] CYP3A4, ABCB1, SLCO1B1 ABCB1, ABCC3 3 1 DDI potential code and clinical relevance: Interaction unlikely or known minor interaction not requiring modification to therapy. Possible interaction based on pharmacology of the drug. No modification to therapy but monitor closely for signs of toxicity. Potential for significant interaction based on pharmacology of the drug. No modification to therapy but monitor closely for signs of toxicity. Consider therapy modification if unable to monitor closely.

Possible interaction based on pharmacology of the drug. No modification to therapy but monitor closely for signs of toxicity. Potential for significant interaction based on pharmacology of the drug. No modification to therapy but monitor closely for signs of toxicity. Consider therapy modification if unable to monitor closely. Potential for clinically significant interaction based on pharmacology of the drug or known interaction. Need for dose adjustment or consideration of therapy modification. Major clinically significant interaction or potential critical interaction. Co-administration is contraindicated. ARV: antiretroviral; ABC: ATP-binding cassette sub-family/member; ALDH: alcohol dehydrogenase; CYP: cytochrome P450; SLC: sodium-coupled nucleoside transport family/member; SLCO: solute carrier organic anion transporter family/member; UGT: uridine 5'-diphospho-glucuronosyltransferase. * Isozyme not specified. • When used as a ritonavir-boosted PI. Original table modified for this publication. Rudek MA, Flexner C, Ambinder RF. Use of antineoplastic agents in patients with cancer who have HIV/AIDS. Lancet Oncol 2011; 12:905. Table used with the permission of Elsevier Inc. All rights reserved. References: Walsh JS, Reese MJ, Thurmond LM. The metabolic activation of abacavir by human liver cytosol and expressed human alcohol dehydrogenase isozymes. Chem Biol Interact 2002; 142:135. Yuen GJ, Weller S, Pakes GE. A review of the pharmacokinetics of abacavir. Clin Pharmacokinet 2008; 47:351. McDowell JA, Chittick GE, Ravitch JR, et al. Pharmacokinetics of [(14)C]abacavir, a human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitor, administered in a single oral dose to HIV-1-infected adults: a mass balance study. Antimicrob Agents Chemother 1999; 43:2855. Weiss, J, Haefeli, WE. Impact of ATP-binding cassette transporters on human immunodeficiency virus therapy. International review of cell and molecular biology 2010; 280:219. Ray AS, Olson L, Fridland A. Role of purine nucleoside phosphorylase in interactions between 2',3'-dideoxyinosine and allopurinol, ganciclovir, or tenofovir. Antimicrob Agents Chemother 2004; 48:1089. Zong J, Chittick GE, Wang LH, et al. Pharmacokinetic evaluation of emtricitabine in combination with other nucleoside antivirals in healthy volunteers. J Clin Pharmacol 2007; 47:877.

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