Table 3.

Cardiac interactions and side effects of drugs commonly used in HIV therapy

Class	Cardiac drug interactions	Cardiac side effects
Antiretroviral Nucleoside (and nucleotide) reverse transcriptase inhibitors Abacavir (ABC), Didanosine (ddI), Emtricitabine (FTC) Lamivudine (3TC), Stavudine (d4T), Tenofovir (TDF), Zalcitabine (ddC), Zidovudine (ZDV, AZT)	Zidovudine and dipyridamole Stavdine and DDI	Rare: lactic acidosis, hypotension Accelerated risk with cardiopulmonary bypass Zidovudine: skeletal muscle myopathy, myocarditis Mitochondrial toxicity with lipodystrophy
Non-nucleoside reverse transcriptase inhibitors Delavirdine (DLV), Efavirenz (EFV), Nevirapine (NVP), Rilpivirine (RPV)	Calcium channel blockers, warfarin, β-blockers, nifedipine, quinidine, steroids, theophylline. Delavirdine can cause serious toxic effects if given with antiarrhythmic drugs and calcium channel blockers	Arrhythmia
Protease inhibitors   Amprenavir (APV), Atazanavir (ATV), Darunavir (DRV), Fosamprenavir (FPV) Indinavir (IDV), Lopinavir/ritonavir (LPV/r), Nelfinavir (NFV), Ritonavir (RTV), Saquinavir (SQV), Tipranavir (TPV)	Metabolized by cytochrome P450 and interact with other drugs metabolized through this pathway, such as selected antimicrobials, antidepressant and antihistamine agents, cisapride, HMG CoA reductase inhibitors (lovastatin, simvastatin), and sildenafil. Potentially dangerous interactions that require close monitoring or dose adjustment can occur with amiodarone, disopyramide, flecainide, lidocaine, mexiletine, propafenone, and quinidine. Ranolazine (1.8–2.3× increase in Ranolazine level) Ritonavir is the most potent cytochrome activator (CYP3A) and P-glycoprotein inhibitor and is most likely to interact. Indinavir, amprenavir, and nelfinavir are moderate. Saquinavir has the lowest probability to interact Calcium channel blockers, prednisone, quinine, β-blockers (1.5- to 3-fold increase). Decreases theophylline concentrations	Implicated in premature atherosclerosis, dyslipidemia, insulin resistance, diabetes mellitus, fat wasting, and redistribution Abacavir may be associated with increased risk of MI13
Integrase strand transfer inhibitors (INSTIs) Elvitegravir (EVG), Raltegravir (RAL)
CCR5 antagonists Maraviroc
Fusion inhibitor Enfuvirtide	–
Anti-infective antibiotics	Rifampin: Reduces therapeutic effect of digoxin by inducing intestinal P-glycoprotein, reduces protease inhibitor concentration and effect Erythromycin: Cytochrome P450 metabolism and drug interactions Trimethoprim-sulfamethoxazole: (Bactrim) increases warfarin effects	Erythromycin: Orthostatic hypotension, ventricular tachycardia, bradycardia, Torsades (with drug interactions) Clarithromycin: QT prolongation and Torsades de Pointes Trimethoprim-sulfamethoxazole: Orthostatic hypotension, anaphylaxis, QT prolongation, Torsades de Pointes, hypokalemia Sparfloxacin (fluoroquinolones): QT prolongation
Antifungal agents	Amphotericin B: Digoxin toxicity Ketoconazole or itraconazole: Cytochrome P450 metabolism and drug interactions—increases levels of sildenafil, warfarin, HMG CoA reductase inhibitors, nifedipine, digoxin	Amphotericin B: Hypertension, arrhythmia, renal failure, hypokalemia, thrombophlebitis, bradycardia, angioedema, dilated cardiomyopathy. Liposomal formulations still have the potential for electrolyte imbalance and QT prolongation Ketoconazole, fluconazole, itraconazole: QT prolongation and torsades de pointes
Antiviral agents	Ganciclovir: Zidovudine	Foscarnet: Reversible cardiac failure, electrolyte abnormalities Ganciclovir: Ventricular tachycardia, hypotension
Antiparasitic		Pentamidine: Hypotension, QT prolongation, arrhythmias (Torsades de Pointes), ventricular tachycardia, hyperglycemia, hypoglycemia, sudden death. These effects are enhanced by hypomagnesemia and hypokalemia
Chemotherapy agents	Vincristine, doxorubicin: Decrease digoxin level	Vincristine: Arrhythmia, myocardial infarction, cardiomyopathy, autonomic neuropathy Recombinant human interferon-alpha: Hypertension, hypotension, tachycardia, acute coronary events, dilated cardiomyopathy, arrhythmias, sudden death, atrioventricular block, peripheral vasodilation. Contraindicated in patients with unstable angina or recent myocardial infarction Interleukin-2: Hypotension, arrhythmia, sudden death, myocardial infarction, dilated cardiomyopathy, capillary leak, thyroid alterations Anthracyclines (doxorubicin, daunorubicin, mitoxantrone): Myocarditis, cardiomyopathy Liposomal anthracyclines: As above for doxorubicin and also vasculitis
Pentoxifylline		Pentoxifylline: Decreased triglyceride levels, arrhythmias, chest pain Megace: Edema, thrombophlebitis, hyperglycemia
Megestrol acetate (Megace)		Epoetin alpha (erythropoietin): Hypertension, ventricular dysfunction
Methadone		Prolonged QT interval
Amphetamines		Increased heart rate and blood pressure

Modified with permission from Fisher SD, Lipshultz SE. Chapter 72: Cardiovascular abnormalities in HIV-infected individuals. In: Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, Ninth Edition. Editors: Bonow RO, Mann DL, Zipes DP, Libby P. Philadelphia: Elsevier Saunders. 1618–27. 2011 ISBN: 978-1-4377-0398-6.