Amiodarone: [P] Increased serum phenytoin concentration; possible reduction in serum amiodarone concentration. Capecitabine: [NE] Increased phenytoin plasma concentrations. Chloramphenicol: [P] Increased phenytoin plasma concentrations. Felbamate: [P] Increased phenytoin plasma concentrations. Fluorouracil: [NE] Increased phenytoin plasma concentrations.
Fluvoxamine: [NP] Increased phenytoin plasma concentrations. Isoniazid: [NP] Increased serum phenytoin; problem primarily with slow acetylators of isoniazid.
Metronidazole: [NP] Increased phenytoin plasma concentrations. Sulfamethoxazole: [P] Increased phenytoin plasma concentrations. Ticlopidine: [NP] Increased phenytoin plasma concentrations. See also Azole antifungals; Cimetidine; Disulfiram.
Drugs that enhance phenytoin metabolism:
Bosentan: [P] Decreased phenytoin plasma concentrations. Carbamazepine: [P] Decreased phenytoin plasma concentrations. Rifampin: [P] Decreased phenytoin plasma concentrations. St. John’s wort: [P] Decreased phenytoin plasma concentrations. See also Barbiturates.
Antivirals: [P] Amprenavir, atazanavir, boceprevir, darunavir, delavirdine, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, simeprevir, and telaprevir inhibit the metabolism of pimozide.
Boceprevir: [P] Decreased metabolism of pimozide. Cobicistat: [P] Decreased metabolism of pimozide. Conivaptan: [P] Decreased metabolism of pimozide. Kinase inhibitors: [P] Decreased metabolism of pimozide with ceritinib, dasatinib, imatinib, idelalisib, and lapatinib. Nefazodone: [NP] Decreased pimozide metabolism. See also Azole antifungals; Cyclosporine; Macrolides.
ACE inhibitors (ACEIs): [NP] Additive hyperkalemic effect. Angiotensin II receptor blockers (ARBs): [NP] Additive hyperkalemic effect. Antivirals: [P] Amprenavir, atazanavir, boceprevir, darunavir, delavirdine, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, simeprevir, and telaprevir inhibit the metabolism of eplerenone. Boceprevir: [P] Decreased metabolism of eplerenone. Cobicistat: [P] Decreased metabolism of eplerenone. Conivaptan: [P] Decreased metabolism of eplerenone.
E, Expected; HP, Highly predictable. Interaction occurs in almost all patients receiving the interacting combination; P, Predictable. Interaction occurs in most patients receiving the combination; NP, Not predictable. Interaction occurs only in some patients receiving the combination; NE, Not established. Insufficient data available on which to base estimate of predictability.
TABLE 66–1 Important drug interactions.
Potassium-sparing diuretics (amiloride, eplerenone, spironolactone, triamterene) (cont.)
Probenecid Interference with renal excretion of drugs that undergo active tubular secretion, especially weak acids. Inhibition of glucuronide conjugation of other drugs.
Quinidine Substrate of CYP3A4. Inhibits CYP2D6. Renal excretion susceptible to changes in urine pH. Additive effects with other agents that prolong the QTc interval.