Duloxetine: A Balanced and Selective Norepinephrine and Serotonin-Reuptake Inhibitor

Anders D. Westanmo; Jon Gayken; Robert Haight


Am J Health Syst Pharm. 2005;62(23):2481-2490. 

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Hepatic or Renal Insufficiency

Any degree of hepatic insufficiency is a contraindication to treatment with duloxetine. Because duloxetine and alcohol may interact to cause liver injury, duloxetine should not be used in patients with substantial alcohol use.[74] When a single dose of duloxetine 20 mg was administered to patients with hepatic dysfunction, mean plasma clearance was 15% of that observed in patients without hepatic dysfunction, AUC increased fivefold, and the half-life was threefold longer.[24] During postmarketing surveillance, cases of hepatitis with abdominal pain, hepatomegaly, and increased transaminase levels (up to more than 20 times the upper limit of normal) with or without jaundice have been reported. Cholestatic jaundice with minimal increases in transaminase levels have also been reported.[74] Duloxetine is not recommended in patients with a creatinine clearance (CLcr) of < 30 mL/min, and patients with renal insufficiency should be monitored closely during treatment with duloxetine.[25] After a single dose, the duloxetine AUC increased twofold, while the AUCs of two of the major glucuronide metabolites were sevenfold and ninefold higher in patients with renal dysfunction than in healthy individuals.[25]

Duloxetine is in pregnancy category C, and dosage may need to be tapered and the drug discontinued in pregnant women.[25]