TABLE 66–1 Important drug interactions. (Continued)
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.
Antidepressants, tricyclic and heterocyclic
Inhibition of transmitter uptake into 5-HT and NE neurons. Antimuscarinic effects may be additive with other antimuscarinic drugs. Susceptible to induction and inhibition of metabolism via CYP2D6, CYP3A4, and other CYP450 enzymes.
Inhibition of CYP3A4 (itraconazole = ketoconazole > posaconazole > voriconazole > fluconazole). Inhibition of CYP2C9 (fluconazole, voriconazole). Inhibition of P-glycoprotein (itraconazole, ketoconazole, posaconazole). Susceptible to enzyme inducers (itraconazole, ketoconazole, voriconazole).
Amiodarone: [P] Decreased antidepressant metabolism. Expect similar interactions with dronedarone. Barbiturates: [P] Increased antidepressant metabolism. Bupropion: [NE] Decreased antidepressant metabolism. Carbamazepine: [NP] Enhanced metabolism of antidepressants. Cimetidine: [P] Decreased antidepressant metabolism. Clonidine: [P] Decreased clonidine antihypertensive effect. Diphenhydramine: [P] Decreased metabolism of antidepressants metabolized by CYP2D6. Guanadrel: [P] Decreased uptake of guanadrel into sites of action.
Haloperidol: [P] Decreased metabolism of antidepressants metabolized by CYP2D6. Monoamine oxidase inhibitors (MAOIs): [NP] Some cases of excitation, hyperpyrexia, mania, and convulsions, especially with serotonergic antidepressants such as clomipramine and imipramine, but many patients have received combination without ill effects.
Quinidine: [NP] Decreased metabolism of antidepressants metabolized by CYP2D6. Rifampin: [P] Increased antidepressant metabolism. Selective serotonin reuptake inhibitors (SSRIs): [P] Fluoxetine and paroxetine inhibit
CYP2D6 and decrease metabolism of antidepressants metabolized by this enzyme (eg, desipramine). Citalopram, sertraline, and fluvoxamine are only weak inhibitors of CYP2D6, but fluvoxamine inhibits CYP1A2 and CYP3A4 and thus can inhibit the metabolism of antidepressants metabolized by these enzymes.
Sympathomimetics: [P] Increased pressor response to norepinephrine, epinephrine, and phenylephrine.
Terbinafine: [P] Decreased antidepressant metabolism. Antivirals: [P] Decreased metabolism of amprenavir, atazanavir, boceprevir, daclatasvir, darunavir, delavirdine, etravirine, fosamprenavir, indinavir, lopinavir, maraviroc, nelfinavir, rilpivirine, ritonavir, saquinavir, and tipranavir.