Colchicine; Cyclosporine; Digitalis glycosides; HMG-CoA reductase inhibitors. Anorexiants: [P] Hypertensive episodes due to release of stored norepinephrine (benzphetamine, diethylpropion, mazindol, phendimetrazine, phentermine). Antidiabetic agents: [P] Additive hypoglycemic effect. Buspirone: [NE] Possible serotonin syndrome; avoid concurrent use. Dextromethorphan: [NP] Severe reactions (hyperpyrexia, coma, death) have been reported. Guanethidine: [P] Reversal of the hypotensive action of guanethidine. Mirtazapine: [NE] Possible serotonin syndrome; avoid concurrent use. Nefazodone: [NP] Possible serotonin syndrome; avoid concurrent use. Opioid analgesics: [NP] Some patients develop hypertension, rigidity, excitation; meperidine more likely to interact than morphine; avoid concurrent use. Phenylephrine: [P] Hypertensive episode, since phenylephrine is metabolized by monoamine oxidase. Selective serotonin reuptake inhibitors (SSRIs): [P] Fatalities have occurred due to serotonin syndrome; contraindicated in patients taking MAOIs; avoid concurrent use. Sibutramine: [NE] Possible serotonin syndrome; avoid concurrent use. Sympathomimetics (indirect-acting): [HP] Hypertensive episode due to release of stored norepinephrine (amphetamines, ephedrine, isometheptene, phenylpropanolamine, pseudoephedrine). Tramadol: [NP] Possible serotonin syndrome; avoid concurrent use. Venlafaxine: [NP] Possible serotonin syndrome; avoid concurrent use. See also Antidepressants, tricyclic and heterocyclic; Levodopa.
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.
Prostaglandin inhibition may result in reduced renal sodium excretion, impaired resistance to hypertensive stimuli, and reduced renal lithium excretion. Most NSAIDs inhibit platelet function; may increase likelihood of bleeding due to other drugs that impair hemostasis.
Opioid analgesics that are substrates of CYP3A4 (alfentanil, fentanyl, oxycodone, sufentanil, and to a lesser extent methadone) are susceptible to inhibitors and inducers. Methadone is primarily metabolized by CYP2B6. Additive central nervous system depression with other central nervous system depressants.
Induces hepatic microsomal drug metabolism. Susceptible to inhibition of metabolism by CYP2C9 and, to a lesser extent, CYP2C19.
ACE inhibitors (ACEIs): [P] Decreased antihypertensive response. Angiotensin II receptor blockers (ARBs): [P] Decreased antihypertensive response. Furosemide: [P] Decreased diuretic, natriuretic, and antihypertensive response to furosemide. Hydralazine: [NE] Decreased antihypertensive response to hydralazine. Methotrexate: [NP] Possibly increased methotrexate toxicity (especially with anticancer doses of methotrexate).