Drug Interactions between Cymbalta and patiromer

GENERALLY AVOID: Use of duloxetine in conjunction with chronic alcohol consumption may potentiate the risk of liver injury. Duloxetine alone can increase serum transaminase levels. In clinical trials, 0.3% of patients discontinued duloxetine due to liver transaminase elevations. The median time to detection was about two months. Three duloxetine-treated patients had liver injury as manifested by transaminase and bilirubin elevations, with evidence of obstruction. Substantial intercurrent ethanol use was present in each of these cases, which may have contributed to the abnormalities observed. Duloxetine does not appear to enhance the central nervous system effects of alcohol. When duloxetine and ethanol were administered several hours apart so that peak concentrations of each would coincide, duloxetine did not increase the impairment of mental and motor skills caused by alcohol.

MANAGEMENT: Due to the risk of liver injury, patients prescribed duloxetine should be counseled to avoid excessive use of alcohol. Duloxetine should generally not be prescribed to patients with substantial alcohol use.

ADJUST DOSING INTERVAL: Patiromer can bind to some orally administered drugs, which may decrease their gastrointestinal absorption and reduce their effectiveness. According to the manufacturer, out of 28 drugs that were tested in in vitro binding studies, 14 did not show an interaction with patiromer (acetylsalicylic acid, allopurinol, amoxicillin, apixaban, atorvastatin, cephalexin, digoxin, glipizide, lisinopril, phenytoin, riboflavin, rivaroxaban, spironolactone, and valsartan). Twelve of the 14 drugs that did show an in vitro interaction were subsequently tested in in vivo studies with healthy volunteers, which revealed no changes in systemic exposure when coadministered with patiromer (amlodipine, cinacalcet, clopidogrel, furosemide, lithium, metoprolol, trimethoprim, verapamil, and warfarin). Patiromer was found to decrease systemic exposure of coadministered ciprofloxacin, levothyroxine, and metformin. However, no significant interaction occurred when patiromer and these drugs were dosed 3 hours apart.

MANAGEMENT: Patiromer should be administered with food at least 3 hours before or 3 hours after other oral medications. Alternatives to patiromer or the other medications should be considered if adequate dosing separation is not possible. Otherwise, clinical response and/or blood levels should be monitored where possible.