duloxetine CYMBALTA

Class: SNRI
FDA Indications: MDD, GAD, Fibromyalgia, Diabetic Peripheral Neuropathic Pain, Chronic Musculoskeletal Pain
Off-Label Use: Stress Urinary Incontinence, Lewy Body Dementia
Prescribing
Forms: 20, 30, 60mg delayed-release capsule
Dose Range: 30-60 mg/day
Starting: 30 mg QHS, with target dose of 30 mg BID. There is no evidence that doses > 60 mg qd confer any additional benefits.
Stopping: Gradually reduce dosage to avoid discontinuation symptoms.

NAMI drug fact sheet

Precautions
Contraindications: Concomitant use of MAOIs
Serious Side Effects: Serotonin syndrome; ↑ risk of SI in children and young adults; may impair platelet aggregation; SIADH; hepatitis in patients with histories of liver disease; transaminitis (0.3%), hyponatremia
Side Effects: sedation/somnolence, hyperhidrosis, nausea, constipation, fatigue, decreased appetite, xerostomia
Pharmacodynamics
1° MOA: Serotonin norepinephrine reuptake inhibitor
Target: SERT, NET
Pharmacokinetics
t½: 12 (8-17)° TMAX: 6°
Substrate of: 2D6, 1A2
Inhibits: 2D6 (moderate); Induces: ∅
Active Metabolites: ∅
DDIs
  • - DO NOT CO-PRESCRIBE WITH MAOIs (need a 14-day washout period)
  • - 2D6 & 1A2 inhibitors can ↑ serum levels
Misc
  • - many consider first-line for depressed patients with somatic pain
  • - no evidence of a dose-response effect
  • - from most to least noradrenergic: levomilnacipran (1:2, 5HT:NE ratio) >> duloxetine (10:1) > desvenlafaxine (12:1) > venlafaxine (30:1)
  • - less risk of hypertension than venlafaxine
  • - significant discontinuation reactions on a par with venlafaxine
Special Populations

Category C—Human Data Suggest Risk in 3rd Trimester

RID < 1%, the long-term effects on neurobehavior and cognitive development from exposure to potent SNRIs and SSRIs during a period of rapid CNS development have not been adequately studied. Therefore, the best course is to avoid duloxetine, if possible, during nursing. In 2001, the American Academy of Pediatrics classified antidepressants as drugs for which the effect on nursing infants is unknown but may be of concern.

Start at a 30 mg qd for 2 weeks before considering ↑ to 60 mg target dose; watch for hypoNa+ at doses > 60 mg in the elderly

Avoid use in patients with severe renal impairment, GFR <30 mL/min

Avoid use in patients with chronic liver disease or cirrhosis

References
Cymbalta Package Insert
Lippincott Reviews: Pharmacology 6th Ed
Serotonin Norepinephrine Reuptake Inhibitors: Similarities And Differences
Serotonin Norepinephrine Reuptake Inhibitors: A Pharmacological Comparison
Drugs In Pregnancy And Lactation 11th Ed

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Last updated August 16 2023 14:43:53. Disclaimer: This website does not provide medical advice, nor is it a substitute for clinical judgment.