Selective serotonin reuptake inhibitors (SSRIs): [P] Increased risk of bleeding due to platelet inhibition. Thiazide diuretics: [P] Decreased diuretic, natriuretic, and antihypertensive response. Triamterene: [NE] Decreased renal function noted with triamterene plus indomethacin in both healthy subjects and patients. See also Anticoagulants, oral; β-Adrenoceptor blockers; Lithium.
Amiodarone: [NP] Decreased CYP3A4-dependent opioid metabolism. Expect similar interactions with dronedarone. Antivirals: [P] Amprenavir, atazanavir, boceprevir, darunavir, delavirdine, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, simeprevir, and telaprevir inhibit the metabolism of CYP3A4-dependent opioids. Boceprevir: [P] Decreased metabolism of CYP3A4-dependent opioids. Bosentan: [P] Increased CYP3A4-dependent opioid metabolism. Cobicistat: [P] Decreased metabolism of CYP3A4-dependent opioids. Conivaptan: [P] Decreased metabolism of CYP3A4-dependent opioids.
Efavirenz: [P] Increased metabolism of CYP3A4-dependent opioids. Kinase inhibitors: [P] Decreased metabolism of CYP3A4-dependent opioid by ceritinib, dasatinib, imatinib, idelalisib, and lapatinib.
Nefazodone: [NP] Decreased CYP3A4-dependent opioid metabolism. Nevirapine: [P] Increased metabolism of CYP3A4-dependent opioids. Phenytoin: [P] Increased CYP3A4-dependent opioid metabolism. Rifampin: [P] Increased CYP3A4-dependent opioid metabolism. St. John’s wort: [NP] Increased CYP3A4-dependent opioid metabolism. See also Azole antifungal agents; Barbiturates; Carbamazepine; Cimetidine; Macrolides;
Monoamine oxidase inhibitors.
Drugs whose metabolism is stimulated by phenytoin:
Corticosteroids: [P] Decreased serum corticosteroid levels. Doxycycline: [P] Decreased serum doxycycline levels. Mexiletine: [NE] Decreased serum mexiletine levels. Quinidine: [P] Decreased serum quinidine levels. Theophylline: [NP] Decreased serum theophylline levels. See also Calcium channel blockers; Cyclosporine; Estrogens; Opioid analgesics.
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.
Phenytoin (cont.)
Pimozide Susceptible to CYP3A4 inhibitors; may exhibit additive effects with other agents that prolong QTc interval.
Drugs that inhibit phenytoin metabolism: