Drug Interactions

Abacavir: Protease Inhibitors may decrease the serum concentration of Abacavir. Risk C: Monitor therapy

Alfuzosin: Protease Inhibitors may increase the serum concentration of Alfuzosin. Risk X: Avoid combination

ALPRAZolam: Protease Inhibitors may increase the serum concentration of ALPRAZolam. Management: Concurrent use of alprazolam with indinavir is contraindicated. All patients receiving such a combination should be monitored closely for excessive response to alprazolam. Risk C: Monitor therapy

Amiodarone: Protease Inhibitors may decrease the metabolism of Amiodarone. Risk X: Avoid combination

Antacids: May decrease the absorption of Protease Inhibitors. Risk C: Monitor therapy

Antifungal Agents (Azole Derivatives, Systemic): May increase the serum concentration of Protease Inhibitors. Protease Inhibitors may increase the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Management: Limit indinavir adult dose to 600 mg every 8 hours with itraconazole or ketoconazole. With ritonavir, limit ketoconazole adult dose to 200 mg/day. Limit fluconazole, itraconazole, and ketoconazole to 200 mg (adult dose) with tipranavir/ritonavir. Risk D: Consider therapy modification

Atomoxetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Atomoxetine. Management: Initiate atomoxetine at a reduced dose (adult doses -- patients up to 70kg: 0.5mg/kg/day; patients 70kg or more: 40mg/day) in patients receiving a strong CYP2D6 inhibitor. Risk D: Consider therapy modification

Calcium Channel Blockers (Dihydropyridine): Protease Inhibitors may decrease the metabolism of Calcium Channel Blockers (Dihydropyridine). Exceptions: Clevidipine. Risk D: Consider therapy modification

Calcium Channel Blockers (Nondihydropyridine): Protease Inhibitors may decrease the metabolism of Calcium Channel Blockers (Nondihydropyridine). Increased serum concentrations of the calcium channel blocker may increase risk of AV nodal blockade. Management: Avoid concurrent use when possible. If this combination is used, monitor for evidence of toxicity. The manufacturer of atazanavir recommends that a 50% dose reduction for diltiazem be considered. Risk D: Consider therapy modification

CarBAMazepine: May increase the metabolism of Protease Inhibitors. Protease Inhibitors may decrease the metabolism of CarBAMazepine. Risk D: Consider therapy modification

Cisapride: Protease Inhibitors may decrease the metabolism of Cisapride. The resultant increase in serum cisapride concentrations may result in QTc prolongation and malignant cardiac arrhythmias. Risk X: Avoid combination

Clarithromycin: Protease Inhibitors may diminish the therapeutic effect of Clarithromycin. Specifically, certain protease inhibitors may decrease formation of the active 14-hydroxy-clarithromycin metabolite, which may negatively impact clarithromycin effectiveness vs. H. influenzae and other non-MAC infections. Protease Inhibitors may increase the serum concentration of Clarithromycin. Clarithromycin dose adjustment in renally impaired patients may be needed. Clarithromycin may increase the serum concentration of Protease Inhibitors. Risk D: Consider therapy modification

Codeine: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk D: Consider therapy modification

Contraceptives (Estrogens): May diminish the therapeutic effect of Protease Inhibitors. Protease Inhibitors may decrease the serum concentration of Contraceptives (Estrogens). Management: Use of an alternative, non-hormone-based contraceptive is recommended. Risk D: Consider therapy modification

Corticosteroids (Orally Inhaled): Protease Inhibitors may decrease the metabolism of Corticosteroids (Orally Inhaled). Exceptions: Beclomethasone; Beclomethasone (Oral Inhalation); Flunisolide; Flunisolide (Oral Inhalation); Triamcinolone; Triamcinolone (Systemic, Oral Inhalation). Risk D: Consider therapy modification

CycloSPORINE: Protease Inhibitors may increase the serum concentration of CycloSPORINE. CycloSPORINE may increase the serum concentration of Protease Inhibitors. Risk D: Consider therapy modification

CycloSPORINE (Systemic): Protease Inhibitors may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Protease Inhibitors. Risk D: Consider therapy modification

CYP2D6 Substrates: CYP2D6 Inhibitors (Strong) may decrease the metabolism of CYP2D6 Substrates. Exceptions: Tamoxifen. Risk D: Consider therapy modification

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy

Dabigatran Etexilate: P-Glycoprotein Inducers may decrease the serum concentration of Dabigatran Etexilate. Risk C: Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy

Delavirdine: Protease Inhibitors may decrease the serum concentration of Delavirdine. Delavirdine may increase the serum concentration of Protease Inhibitors. Risk D: Consider therapy modification

Didanosine: Tipranavir may decrease the serum concentration of Didanosine. Management: It is recommended that didanosine be administered at least 2 hours apart from tipranavir in order to minimize any potential dosage form-related interaction. Risk D: Consider therapy modification

Digoxin: Protease Inhibitors may increase the serum concentration of Digoxin. Increased serum concentrations of digoxin may increase risk of AV nodal blockade. Risk C: Monitor therapy

Disulfiram: May enhance the adverse/toxic effect of Tipranavir. Risk D: Consider therapy modification

Divalproex: Protease Inhibitors may decrease the serum concentration of Divalproex. Risk C: Monitor therapy

Efavirenz: May increase the metabolism of Protease Inhibitors. This specifically includes amprenavir, indinavir, and saquinavir. Efavirenz may increase the serum concentration of Protease Inhibitors. This specifically includes nelfinavir and ritonavir. Risk D: Consider therapy modification

Enfuvirtide: Protease Inhibitors may increase the serum concentration of Enfuvirtide. Enfuvirtide may increase the serum concentration of Protease Inhibitors. Risk C: Monitor therapy

Eplerenone: Protease Inhibitors may decrease the metabolism of Eplerenone. Risk C: Monitor therapy

Ergot Derivatives: Protease Inhibitors may increase the serum concentration of Ergot Derivatives. Exceptions: Cabergoline. Risk X: Avoid combination

Estrogen Derivatives: May enhance the dermatologic adverse effect of Tipranavir. The combination of tipranavir/ritonavir and ethinyl estradiol/norethindrone was associated with a high incidence of skin rash. Tipranavir may decrease the serum concentration of Estrogen Derivatives. Management: Women using hormonal contraceptives should consider alternative, non-hormonal forms of contraception. Risk D: Consider therapy modification

Etravirine: Tipranavir may decrease the serum concentration of Etravirine. Risk X: Avoid combination

Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy

Flecainide: Tipranavir may increase the serum concentration of Flecainide. Risk X: Avoid combination

Fusidic Acid: Protease Inhibitors may decrease the metabolism of Fusidic Acid. Fusidic Acid may decrease the metabolism of Protease Inhibitors. Risk D: Consider therapy modification

Garlic: May decrease the serum concentration of Protease Inhibitors. Risk C: Monitor therapy

HMG-CoA Reductase Inhibitors: Protease Inhibitors may increase the serum concentration of HMG-CoA Reductase Inhibitors. Limited data suggest pravastatin may slightly decrease protease inhibitor concentrations. Management: Lovastatin and simvastatin are contraindicated with protease inhibitors; also, avoid rosuvastatin with indinavir. Use lowest possible HMG-CoA reductase inhibitor dose and monitor for signs of toxicity if these agents are used concomitantly. Exceptions: Fluvastatin. Risk D: Consider therapy modification

Lovastatin: Protease Inhibitors may increase the serum concentration of Lovastatin. Risk X: Avoid combination

Meperidine: Protease Inhibitors may enhance the adverse/toxic effect of Meperidine. Protease Inhibitors may decrease the serum concentration of Meperidine. Concentrations of the toxic Normeperidine metabolite may be increased. Risk D: Consider therapy modification

Methadone: Protease Inhibitors may decrease the serum concentration of Methadone. Risk C: Monitor therapy

MetroNIDAZOLE: May enhance the adverse/toxic effect of Tipranavir. Risk C: Monitor therapy

MetroNIDAZOLE (Systemic): May enhance the adverse/toxic effect of Tipranavir. A disulfiram-like reaction may occur due to the alcohol contained in tipranavir capsules. Risk C: Monitor therapy

MetroNIDAZOLE (Topical): May enhance the adverse/toxic effect of Tipranavir. Risk C: Monitor therapy

Midazolam: Protease Inhibitors may increase the serum concentration of Midazolam. Management: Oral midazolam contraindicated with all protease inhibitors. IV midazolam contraindicated with fosamprenavir and nelfinavir; other protease inhibitors recommend caution, close monitoring, and consideration of lower IV midazolam doses with concurrent use. Risk X: Avoid combination

Nebivolol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Nebivolol. Risk C: Monitor therapy

Nefazodone: Protease Inhibitors may increase the serum concentration of Nefazodone. Risk C: Monitor therapy

Nevirapine: May increase the metabolism of Protease Inhibitors. Risk D: Consider therapy modification

P-Glycoprotein Substrates: P-Glycoprotein Inducers may decrease the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy

PHENobarbital: May decrease the serum concentration of Tipranavir. Tipranavir may decrease the serum concentration of PHENobarbital. Risk D: Consider therapy modification

Phenytoin: May decrease the serum concentration of Tipranavir. Tipranavir may decrease the serum concentration of Phenytoin. Risk D: Consider therapy modification

Pimozide: Protease Inhibitors may decrease the metabolism of Pimozide. Risk X: Avoid combination

Propafenone: Tipranavir may increase the serum concentration of Propafenone. Risk X: Avoid combination

Protease Inhibitors: May increase the serum concentration of other Protease Inhibitors. Management: Atazanavir--indinavir combination contraindicated. Tipranavir/ritonavir or atazanavir/ritonavir not recommended with other protease inhibitors. Other combos may require dose changes. Risk D: Consider therapy modification

Proton Pump Inhibitors: Tipranavir may decrease the serum concentration of Proton Pump Inhibitors. These data are derived from studies with Ritonavir-boosted Tipranavir. Risk C: Monitor therapy

QuiNIDine: Protease Inhibitors may decrease the metabolism of QuiNIDine. Risk X: Avoid combination

Raltegravir: Tipranavir may decrease the serum concentration of Raltegravir. Risk C: Monitor therapy

Rifamycin Derivatives: Protease Inhibitors may decrease the metabolism of Rifamycin Derivatives. Specifically rifabutin. Rifamycin Derivatives may decrease the serum concentration of Protease Inhibitors. Rifampin administration should be avoided. Dosage adjustments with both rifabutin and the protease inhibitors are necessary if used together. Management: Avoid using rifampin with protease inhibitors. Rifabutin and protease inhibitor dose adjustments will likely be required when using rifabutin together with protease inhibitors; consult specific protease inhibitor(s) prescribing information. Risk D: Consider therapy modification

Sildenafil: Protease Inhibitors may increase the serum concentration of Sildenafil. Management: Erectile dysfunction: sildenafil max = 25 mg/48 hrs with ritonavir, atazanavir, or darunavir; starting dose = 25 mg with other protease inhibitors (adult doses). Contraindicated if sildenafil being used for pulmonary arterial hypertension. Risk D: Consider therapy modification

Simvastatin: Protease Inhibitors may increase the serum concentration of Simvastatin. Risk X: Avoid combination

Sirolimus: Protease Inhibitors may increase the serum concentration of Sirolimus. Risk C: Monitor therapy

St Johns Wort: May increase the metabolism of Protease Inhibitors. Risk X: Avoid combination

St Johns Wort: May decrease the serum concentration of Tipranavir. Risk X: Avoid combination

Tacrolimus: Protease Inhibitors may decrease the metabolism of Tacrolimus. Risk D: Consider therapy modification

Tacrolimus (Systemic): Protease Inhibitors may decrease the metabolism of Tacrolimus (Systemic). Risk D: Consider therapy modification

Tacrolimus (Topical): Protease Inhibitors may decrease the metabolism of Tacrolimus (Topical). Risk C: Monitor therapy

Tamoxifen: CYP2D6 Inhibitors (Strong) may decrease the metabolism of Tamoxifen. Specifically, strong CYP2D6 inhibitors may decrease the formation of highly potent active metabolites. Risk X: Avoid combination

Temsirolimus: Protease Inhibitors may enhance the adverse/toxic effect of Temsirolimus. Levels of sirolimus, the active metabolite, may be increased, likely due to inhibition of CYP-mediated metabolism. Risk D: Consider therapy modification

Tenofovir: May decrease the serum concentration of Protease Inhibitors. Protease Inhibitors may increase the serum concentration of Tenofovir. Risk C: Monitor therapy

Tetrabenazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Management: Tetrabenazine adult dose should be reduced by 50% when starting a strong CYP2D6 inhibitor. Maximum tetrabenazine adult dose is 50 mg/day when used with a strong CYP2D6 inhibitor. Risk D: Consider therapy modification

Theophylline Derivatives: Protease Inhibitors may decrease the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Risk C: Monitor therapy

Thioridazine: CYP2D6 Inhibitors may decrease the metabolism of Thioridazine. Risk X: Avoid combination

TraMADol: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of TraMADol. These CYP2D6 inhibitors may prevent the metabolic conversion of tramadol to its active metabolite that accounts for much of its opioid-like effects. Risk C: Monitor therapy

TraZODone: Protease Inhibitors may increase the serum concentration of TraZODone. Risk D: Consider therapy modification

Triazolam: Protease Inhibitors may increase the serum concentration of Triazolam. Risk X: Avoid combination

Tricyclic Antidepressants: Protease Inhibitors may increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy

Valproic Acid: Protease Inhibitors may decrease the serum concentration of Valproic Acid. Risk C: Monitor therapy

Vardenafil: Protease Inhibitors may increase the serum concentration of Vardenafil. Management: Limit vardenafil adult dose to max of 2.5 mg/72 hrs with ritonavir, atazanavir, or darunavir; limit to max adult dose of 2.5 mg/24 hrs with other protease inhibitors. Risk D: Consider therapy modification

Zidovudine: Protease Inhibitors may decrease the serum concentration of Zidovudine. Risk C: Monitor therapy

Ethanol/Nutrition/Herb Interactions

Ethanol: Capsules contain dehydrated alcohol 7% w/w (0.1 g per capsule)

Herb/Nutraceutical: St Johns wort may decrease the levels/effects of tipranavir/ritonavir; concurrent use is contraindicated. Vitamin E (high dose) may increase the risk of bleeding.