Antiretroviral Contraindications and Drug Interactions

• Concomitant St. John's wort: not recommended.

• May affect, or be affected by, CYP3A inhibitors or inducers and drugs affected by p-glycoprotein (eg, potentiated by ketoconazole, lopinavir/ritonavir, ritonavir, saquinavir, atazanavir; antagonized by rifampin, efavirenz).

• Caution with antihypertensives.

• May cause false (+) ELISA test for HIV.

• Antagonized by rifampin, possibly other strong UGT1A1 inducers. May be potentiated by UGT1A1 inhibitors.

• Caution with other drugs that can cause myopathy (eg, statins).

• CYP3A substrates that may cause serious events if blood levels are elevated (eg, cisapride, pimozide, alprazolam, midazolam, triazolam, ergots).

• Concomitant lovastatin or simvastatin: not recommended.

• May increase levels of antiarrhythmics (eg, quinidine), calcium channel blockers (eg, nifedipine), clarithromycin, rifabutin, indinavir, saquinavir (monitor ALT/AST), amprenavir, amphetamines, trazodone, warfarin, sildenafil, atorvastatin, fluvastatin, immunosuppressants, methadone, fluticasone (long-term use); serious or life-threatening adverse reactions may occur with some of these drugs (avoid or adjust dose).

• Delavirdine levels may be decreased by phenytoin, phenobarbital, carbamazepine, rifabutin, rifampin, chronic H₂ antagonists or PPIs, dexamethasone, St. John's wort: not recommended; didanosine and vice versa (separate dosing by at least 1 hour).

• Delavirdine levels increased by fluoxetine, ketoconazole.

• Absorption reduced by antacids (separate dosing by at least 1 hour).

• Reduce indinavir dose (consider indinavir 600mg three times daily).

• Concomitant cisapride, ergots, midazolam, triazolam, voriconazole.

• Avoid alcohol, other psychoactive and/or hepatotoxic drugs.

• Antagonized by St. John's wort: not recommended.

• Caution with drugs metabolized by, or that affect activity of, CYP2C9, CYP2C19, CYP3A4.

• Efavirenz levels decreased by phenobarbital, rifampin, rifabutin.

• May decrease levels of indinavir (increase indinavir to 1g every 8 hours), amprenavir, clarithromycin, methadone, rifabutin (increase dose: see literature).

• Efavirenz increases nelfinavir, ethinyl estradiol plasma levels.

• Levels of both drugs increased with ritonavir (monitor liver function and for adverse events).

• Levels of both drugs are decreased with saquinavir (do not use as sole protease inhibitor).

• Closely monitor warfarin, anticonvulsants (esp. phenytoin, phenobarbital, carbamazepine), rifabutin, others.

• May cause false (+) cannabis screening test (CEDIA DAU multi-level THC assay).

• Concomitant tipranivir/ritonavir, fosamprenavir/ritonavir, atazanavir/ritonavir, PIs without ritonavir (eg, atazanavir, fosamprenavir, nelfinavir, indinavir), ritonavir (600mg twice daily), NNRTIs (eg, efavirenz, nevirapine, delavirdine): not recommended.

• Avoid rifampin, rifapentine, St. John's wort, carbamazepine, phenytoin, phenobarbital; rifabutin with darunavir/ritonavir.

• May affect, or be affected by, drugs that induce or inhibit, or that are substrates of, CYP3A4, CYP2C9, CYP2C19 (eg, azole antifungals, immunosuppressants); monitor.

• Potentiated by lopinavir/ritonavir.

• May antagonize antiarrhythmics (eg, amiodarone, bepridil, disopyramide, flecainide, lidocaine, mexiletine, propafenone, quinidine) (monitor), sildenafil.

• May potentiate warfarin, diazepam.

• May be antagonized by anticonvulsants, dexamethasone.

• Clarithromycin (consider azithromycin for treating MAC).

• Adjust statin dose (except pravastatin, rosuvastatin).

• Rifabutin (adjust dose with etravirine monotherapy).

• Moderate-to-severe hepatic impairment.

• Potentiated by fluconazole (monitor).

• Antagonizes ketoconazole, oral contraceptives: not recommended (use nonhormonal contraception), clarithromycin (consider alternative).

• Antagonized by St. John's wort, rifampin: not recommended.

• May antagonize methadone (monitor for withdrawal symptoms; increase methadone dose if needed), or drugs metabolized by CYP3A4 or CYP2B6.

• Monitor warfarin, rifabutin, other CYP450 substrates.

• See literature regarding fatal hypersensitivity reactions (which may include fever, rash, fatigue, nausea, vomiting, diarrhea, abdominal pain, or respiratory symptoms); discontinue as soon as suspected; do not restart, regardless of HLA-B*5701 status.

• Moderate or severe hepatic impairment.

• May antagonize methadone.

• May be potentiated by ethanol.

• Triple therapy (once daily regimen) with lamivudine + tenofovir: high rate of early viral non-response (see literature).

• See literature re: fatal hypersensitivity reactions; signs/symptoms include: fever, rash, nausea, vomiting, diarrhea, abdominal pain, malaise/fatigue, or respiratory symptoms; discontinue as soon as suspected; do not restart, regardless of HLA-B*5701 status.

• Hepatic impairment.

• Avoid concomitant zalcitabine or other forms of abacavir, lamivudine.

• Do not combine with other nucleoside/nucleotide reverse transcriptase inhibitors as part of a triple-drug regimen.

• Potentiated by ethanol, TMP/SMX, nelfinavir.

• May antagonize methadone.

• Monitor for treatment-associated toxicities with interferon-alpha with or without ribavirin.

• See literature re: fatal hypersensitivity reactions; signs/symptoms include: fever, rash, nausea, vomiting, diarrhea, abdominal pain, malaise/fatigue, or respiratory symptoms; discontinue as soon as suspected; do not restart, regardless of HLA-B*5701 status.

• Hepatic impairment.

• Avoid zalcitabine, stavudine, doxorubicin, ribavirin, emtricitabine, tenofovir, other forms of abacavir, lamivudine, or zidovudine.

• Abacavir may antagonize methadone.

• TMP/SMX, nelfinavir may increase lamivudine levels.

• Ethanol may increase abacavir levels. Atovaquone, fluconazole, methadone, nelfinavir, probenecid, ritonavir, valproic acid may affect zidovudine levels; monitor.

• Increased hematologic toxicity with ganciclovir, other bone marrow suppressants or cytotoxic agents.

• Triple therapy (once daily regimen) with tenofovir or with didanosine + tenofovir: high rate of early viral non-response (see literature).

• Monitor for treatment-associated toxicities with interferon-alpha with or without ribavirin.

• Extreme caution with pancreatotoxic drugs (eg, alcohol, stavudine, pentamidine): see literature.

• Caution with hydroxyurea, neurotoxic drugs (eg, stavudine).

• Potentiated by allopurinol (not recommended), ganciclovir, tenofovir (reduce dose of didanosine; monitor); increased didanosine toxicities with ribavirin (not recommended).

• Antagonized by methadone.

• For pediatric pwd: avoid magnesium- or aluminum-containing antacids.

• Separate dosing of delavirdine, indinavir, nelfinavir by 1 hour; give drugs affected by gastric pH (eg, ketoconazole, itraconazole) 2 hours prior.

• May antagonize quinolones, tetracyclines. Give at least 6 hours before or 2 hours after ciprofloxacin.

• See literature for dosing with concomitant tenofovir.

• Avoid concomitant drugs that contain emtricitabine or lamivudine.

• Avoid concomitant drugs that contain emtricitabine, tenofovir, lamivudine, or adefovir dipivoxil.

• Potentiates didanosine toxicity (>60kg; reduce dose of didanosine); discontinue didanosine if toxicity develops.

• Monitor drugs that reduce renal function or compete for renal tubular secretion (eg, adefovir dipivoxil, cidofovir, acyclovir, valacyclovir, ganciclovir, valganciclovir).

• Avoid concomitant or recent use of nephrotoxic agents.

• Potentiated by lopinavir/ritonavir, atazanavir; monitor for toxicity.

• Concomitant atazanavir: must give with ritonavir.

• Caution with triple nucleoside-only regimen (high rate of early viral non-response); monitor and consider alternative therapy.

• See literature for dosing of concomitant didanosine or ritonavir.

• Concomitant zalcitabine: not recommended.

• Avoid concomitant drugs that contain lamivudine or emtricitabine.

• Caution with drugs eliminated by active organic cationic secretion (eg, trimethoprim). Increased lamivudine absorption with TMP/SMX (clinical significance unknown).

• Triple therapy (once daily regimen) with abacavir + tenofovir or with didanosine + tenofovir: high rate of early viral non-response (see literature).

• Monitor for treatment-associated toxicities with interferon-alpha with or without ribavirin.

• Avoid concomitant other forms of zalcitabine, stavudine, doxorubicin, ribavirin.

• Bone marrow suppression increased by ganciclovir, interferon-alpha, cytotoxic drugs. TMP/SMX, atovaquone, fluconazole, methadone, probenecid, valproic acid, possibly others may affect lamivudine or zidovudine blood levels (clinical significance unknown); monitor.

• Triple therapy (once daily regimen) with abacavir + tenofovir or with didanosine + tenofovir: high rate of early viral non-response (see literature).

• Monitor for treatment-associated toxicities with interferon-alpha with or without ribavirin.

• Avoid concomitant zidovudine.

• Increased risk of toxicity with neurotoxic, hepatotoxic, or pancreatotoxic drugs (eg, didanosine and/or hydroxyurea); avoid.

• Caution with doxorubicin, ribavirin.

• Monitor for treatment-associated toxicities with interferon-alpha with or without ribavirin.

• Avoid concomitant drugs that contain tenofovir or adefovir dipivoxil.

• Potentiates didanosine toxicity (>60kg; reduce dose of didanosine); discontinue if toxicity develops.

• Monitor drugs that reduce renal function or compete for renal tubular secretion (eg, cidofovir, acyclovir, valacyclovir, ganciclovir, valganciclovir).

• Potentiated by lopinavir/ritonavir, atazanavir; monitor for toxicity.

• Concomitant atazanavir: must give with ritonavir.

• Caution with triple nucleoside-only regimens (high rate of early viral non-response); monitor and consider alternative therapy.

• See literature for dosing of concomitant didanosine or ritonavir.

• Avoid stavudine, doxorubicin, ribavirin, other nucleoside analogues, other forms of zidovudine.

• Caution with other cytotoxic or myelosuppressive drugs (eg, ganciclovir, interferon-alpha, ribavirin).

• Fluconazole, atovaquone, lamivudine, probenecid, valproic acid, methadone increase zidovudine levels.

• Monitor phenytoin.

• May be antagonized by rifampin, ritonavir, nelfinavir.

• Monitor for treatment-associated toxicities with interferon-alpha with or without ribavirin.

• Concomitant nevirapine; other protease inhibitors or fluticasone (atazanavir + ritonavir): not recommended.

• Caution with drugs metabolized by UGT1A1 or CYP3A (eg, parenteral midazolam, calcium channel blockers, statins, immunosuppressants, PDE5 inhibitors: reduce doses of these; max 25mg sildenafil in 48 hrs; max 10mg tadalafil in 72 hrs; max 2.5mg vardenafil in 72 hrs), and CYP2C8 (eg, paclitaxel, repaglinide).

• Potentiated by CYP3A inhibitors.

• Antagonized by CYP3A inducers.

• Use cautiously and monitor diltiazem, antiarrhythmics, others that affect conduction (esp. if metabolized by CYP3A).

• Consider reducing diltiazem or clarithromycin dose by 50%; rifabutin dose by 75%.

• Variable effects on clarithromycin; consider other drugs.

• Plasma levels decreased by drugs that reduce gastric acidity (eg, H₂ blockers). Give proton pump inhibitors 12 hours before atazanavir; avoid in therapy-experienced.

• Give 2 hours before or 1 hour after buffered or enteric coated didanosine.

• Antagonized by tenofovir (see dose).

• Increased risk of lactic acidosis with nucleoside analogues.

• Potentiates saquinavir, trazodone, fluticasone, oral contraceptives, ketoconazole, itraconazole.

• Monitor warfarin, tricyclics, rifabutin, atorvastatin, rosuvastatin, immunosuppressants.

• Voriconazole: not recommended.

• Avoid protease inhibitors other than those studied (lopinavir/ritonavir, saquinavir, indinavir, atazanavir), dexamethasone, fluticasone.

• Potentiates carbamazepine, risperidone, thioridazine, trazodone, desipramine, IV midazolam, rifabutin, digoxin, atorvastatin, pravastatin, rosuvastatin, sildenafil, vardenafil, tadalafil (reduce their doses).

• Potentiates, and is potentiated by, indinavir, ketoconazole, itraconazole.

• Increases efavirenz levels.

• Antagonizes sertraline, paroxetine (monitor levels), ethinyl estradiol, norethindrone (use backup contraception).

• Antagonizes and antagonized by other CYP3A4 substrates (eg, carbamazepine, phenobarbital, phenytoin).

• Antagonized by efavirenz.

• Monitor antiarrhythmics (eg, bepridil, systemic lidocaine, quinidine, amiodarone, flecainide, propafenone), calcium channel blockers, β-blockers, warfarin, digoxin, immunosuppressants (eg, tacrolimus, sirolimus, cyclosporine), methadone (possible opiate withdrawal syndrome).

• Reduce concomitant clarithromycin dose in renal impairment.

• Separate dosing of didanosine.

• Life-threatening arrhythmias possible with bepridil.

• Concomitant nevirapine without ritonavir: not recommended.

• Reduce rifabutin dose by at least ½ (or by 75% if with ritonavir) and monitor for neutropenia (do weekly CBCs).

• Potentiates sildenafil, tadalafil, vardenafil; reduce doses of these.

• May potentiate fluticasone (consider alternative therapy), trazodone (reduce trazodone dose).

• Monitor amiodarone, anticonvulsants (eg, phenytoin), H₂ blockers, immunosuppressants, lidocaine (systemic), quinidine, tricyclics, warfarin, drugs that affect or are affected by CYP3A4 (eg, azole antifungals, benzodiazepines, calcium channel blockers, macrolides, NNRTIs, protease inhibitors, statins, steroids).

• May antagonize, or be antagonized by antacids, hormonal contraceptives (use non-hormonal methods), methadone.

• Concomitant amiodarone, cisapride, triazolam, midazolam, pimozide, ergots.

• Rifampin, St. John's wort, atazanavir, lovastatin, simvastatin: not recommended; caution with other statins metabolized by CYP3A4.

• Potentiates PDE5 inhibitors; reduce sildenafil to max 25mg per 48 hours; reduce tadalafil to max 10mg per 72 hours; reduce vardenafil to max 2.5mg per 24 hours; rifabutin, calcium channel blockers, others metabolized by CYP3A4.

• Plasma levels increased by itraconazole, ketoconazole, delavirdine, CYP3A4 inhibitors.

• Plasma levels reduced by efavirenz, rifabutin; possibly phenobarbital, phenytoin, carbamazepine, dexamethasone, other CYP3A4 inducers.

• Separate dosing of indinavir and didanosine by at least 1 hour and give both on empty stomach.

• Loss of virologic response or resistance with rifampin, St. John's wort.

• Drugs metabolized by CYP3A that may cause serious events if blood levels are elevated (eg, cisapride, ergots, pimozide, midazolam, triazolam).

• Lovastatin, simvastatin, St. John's wort, rifampin, voriconazole: not recommended.

• Potentiates sildenafil, vardenafil, tadalafil (reduce dose of these), statins metabolized by CYP3A (eg, atorvastatin), fluticasone (avoid).

• Avoid oral soln with metronidazole, disulfiram.

• Monitor other antiretrovirals, warfarin.

• Increases levels of antiarrhythmics, dihydropyridine, calcium channel blockers, immunosuppressants (monitor); ketoconazole, itraconazole (avoid high doses); rifabutin (reduce rifabutin dose and monitor); clarithromycin (reduce clarithromycin dose in renal dysfunction), trazodone (reduce trazodone dose).

• Give didanosine 1 hour before or 2 hours after.

• Decreases levels of atovaquone, methadone, estrogen-containing oral contraceptives (use other or back-up contraception).

• Lopinavir levels decreased by anticonvulsants (eg, carbamazepine, phenobarbital, phenytoin), dexamethasone, efavirenz, nevirapine.

• Lopinavir levels may be increased by delavirdine, CYP3A inhibitors.

• May decrease zidovudine or abacavir levels.

• CYP3A substrates that may cause serious events if blood levels are elevated (eg, cisapride, pimozide, midazolam, triazolam, lovastatin, simvastatin, ergots, amiodarone, quinidine).

• Rifampin, St. John's wort: not recommended.

• Potentiates CYP3A substrates (eg, dihydropyridine calcium channel blockers, cyclosporine, tacrolimus, sirolimus, rifabutin, atorvastatin), sildenafil (max 25mg in 48 hours), phenytoin (monitor).

• Nelfinavir levels decreased by CYP3A inducers (eg, phenytoin, rifampin, carbamazepine, phenobarbital) or CYP2C19 inducers.

• Nelfinavir levels increased by CYP3A or CYP2C19 inhibitors.

• Antagonizes methadone, oral contraceptives (use additional or alternative contraception).

• Indinavir, ritonavir, saquinavir increase nelfinavir levels.

• Concomitant azithromycin: monitor for azithromycin toxicity (eg, elevated liver enzymes).

• Amiodarone, bepridil, flecainide, quinidine, propafenone, ergots, midazolam, triazolam, pimozide, cisapride.

• Rifampin, lovastatin, simvastatin, St. John's wort, high-dose or long-term meperidine: not recommended.

• Potentiates sildenafil, vardenafil (reduce sildenafil and vardenafil doses), fluticasone (avoid).

• May be affected by, potentiate, or antagonize drugs that are metabolized by or induce CYP3A4, 2D6, 2C9, 3A, 1A2 or glucuronyl transferase, including: opioids, antiarrhythmics (eg, disopyramide, mexiletine), macrolides, anticoagulants, anticonvulsants, most antidepressants (eg, SSRIs, tricyclics, nefazodone, bupropion), antiemetics (eg, dronabinol), antihypertensives (eg, calcium channel blockers, β-blockers), antiparasitics, antifungals (eg, itraconazole), corticosteroids, indinavir, saquinavir, sulfonylureas, immunosuppressants, neuroleptics, sedative/hypnotics, CNS stimulants, atorvastatin; monitor these and others closely.

• Antagonizes theophylline, oral contraceptives, methadone.

• Separate dosing of didanosine by 2½ hours.

• Avoid metronidazole, disulfiram; ketoconazole >200mg/day.

• Reduce rifabutin dose by at least 3/4.

• Severe hepatic impairment.

• Concomitant amiodarone, bepridil, cisapride, ergots, flecainide, midazolam, pimozide, propafenone, quinidine, rifampin, triazolam.

• Concomitant lovastatin, simvastatin, St. John's wort, garlic capsules: not recommended.

• Plasma levels reduced by efavirenz, nevirapine, rifabutin, possibly other enzyme inducers.

• Consider alternatives to CYP3A4 inducers (eg, carbamazepine, phenobarbital, phenytoin, dexamethasone): not recommended.

• Plasma levels increased by clarithromycin (see literature), indinavir, nelfinavir, lopinavir/ritonavir, ritonavir, delavirdine, itraconazole, ketoconazole.

• Antagonizes methadone, oral contraceptives.

• Potentiates CYP3A4 substrates (eg, calcium channel blockers, atorvastatin, pravastatin, fluvastatin, rosuvastatin, dapsone, warfarin, cyclosporine, tacrolimus, rapamycin, sildenafil, vardenafil, tadalafil); monitor their effects; may need reduced doses.

• Caution with antiarrhythmics (eg, systemic lidocaine), tricyclics, benzodiazepines, fentanyl, nefazodone, others (see literature).

• Moderate to severe hepatic insufficiency (Child-Pugh B–C).

• Concomitant potent CYP3A inducers or substrates (eg, amiodarone, bepridil, flecainide, propafenone, quinidine, rifampin, ergots, cisapride, St. John's wort, lovastatin, simvastatin, pimozide, oral midazolam, triazolam).

• Concomitant fluticasone, amprenavir, lopinavir, saquinavir, or fluconazole, ketoconazole, itraconazole ≥200mg/day: not recommended.

• Avoid metronidazole, disulfiram.

• May be synergistic with enfuvirtide.

• Potentiates PDE5 inhibitors (eg, sildenafil, tadalafil, vardenafil), trazodone, desipramine; reduce dose: see literature.

• Reduce rifabutin dose by 75%.

• Antagonizes estrogens (use non-hormonal contraceptives), methadone, valproic acid, omeprazole.

• Antagonized by carbamazepine, phenobarbital, phenytoin.

• Potentiates atorvastatin, rosuvastatin: use lowest possible dose.

• Monitor hypoglycemics, immunosuppressants, tricyclics, SSRIs, warfarin, drugs that affect or are affected by CYP3A4 (eg, azole antifungals, calcium channel blockers, clarithromycin, NNRTIs, PIs, statins).

• Increased risk of bleeding with concomitant anticoagulants, antiplatelet agents, high-dose Vit.E.

• Separate dosing of didanosine, antacids.

• Oral soln: avoid high-dose Vit.E supplements.