Duloxetine (Cymbalta)

Swallow Cymbalta whole without chewing/crushing or opening onto food/liquid, which can affect the enteric coating. Take without regard to meals.

Major depression: 40 mg/day as 20 mg twice daily to 60 mg/day once daily or 30 mg twice daily. Some patients may start 30 mg daily for 1 week before 60 mg daily. Although 120 mg/day was effective, no additional benefit above 60 mg/day was demonstrated; safety >120 mg/day not adequately evaluated.

Generalized anxiety disorder: usually 60 mg daily, or 30 mg daily for 1 week before 60 mg. No demonstrated extra benefit above 60 mg/day despite 120 mg efficacy. If increasing above 60 mg, use increments of 30 mg daily; safety >120 mg/day not adequately evaluated.

Diabetic peripheral neuropathic pain: 60 mg daily; higher doses provide no significant additional benefit and are less tolerated. Consider lower starting dose when tolerability is a concern. With associated renal disease, consider lower starting dose and gradual titration.

Fibromyalgia: start 30 mg daily for 1 week, then 60 mg daily; some respond to 30 mg. No additional benefit above 60 mg even in nonresponders, with more adverse reactions at higher doses.

Ordinarily do not use in ESRD or severe impairment (CrCl <30 mL/min). Plasma duloxetine and especially metabolite concentrations increase in ESRD requiring dialysis.

Limited ESRD data: after a single 60 mg dose, Cmax/AUC were approximately 100% higher in chronic intermittent HD than normal function, with similar elimination half-life. AUCs of the major urinary metabolites (4-hydroxy duloxetine glucuronide and 5-hydroxy, 6-methoxy duloxetine sulfate) were 7 to 9 times higher and expected to increase with repeated dosing. Population PK suggests CrCl 30 to 80 mL/min does not significantly affect apparent clearance.

Not recommended.