BSN Tracker

duloxetine

Brand: Cymbalta, Drizalma, Irenka

⚠ BBW Prototype: venlafaxine
Drug Class: antidepressant
Drug Family: antidepressant
Subclass: SNRI
Organ Systems: cns

Mechanism of Action

Balanced inhibitor of both SERT and NET (approximately equal potency), unlike venlafaxine's serotonin-preferential profile at low doses; enhances descending pain inhibitory pathways via noradrenergic modulation.

SERTNET

Indications

  • major depressive disorder
  • generalized anxiety disorder
  • diabetic peripheral neuropathy
  • fibromyalgia
  • chronic musculoskeletal pain
  • stress urinary incontinence (international)

Contraindications

  • concurrent MAOIs
  • uncontrolled narrow-angle glaucoma
  • substantial alcohol use (hepatotoxicity risk)
  • end-stage renal disease

Adverse Effects

Common

  • nausea
  • dry mouth
  • somnolence
  • constipation
  • increased sweating
  • dizziness

Serious

  • hepatotoxicity
  • serotonin syndrome
  • suicidal ideation
  • urinary retention
  • hypertension
  • severe skin reactions

Pharmacokinetics (ADME)

Absorption ~50% bioavailability; enteric-coated to protect from gastric acid
Distribution Highly protein-bound (>90%); Vd ~1640 L
Metabolism CYP1A2 and CYP2D6 (primary); avoid in severe hepatic impairment
Excretion Renal (~70%); avoid in ESRD (CrCl <30 mL/min for pain indications)
Half-life 12 hours
Onset 1–2 weeks (partial); 4–6 weeks (full)
Peak 6 hours
Duration 24 hours
Protein Binding >90%
Vd ~1640 L

Drug Interactions

Drug / Agent Mechanism Severity
MAOIs serotonin syndrome major
CYP1A2 inhibitors (fluvoxamine, ciprofloxacin) increase duloxetine levels major
CYP2D6 inhibitors moderately increase duloxetine levels moderate

Nursing Considerations

  1. Monitor LFTs at baseline; avoid in patients with hepatic disease or heavy alcohol use — hepatotoxicity including fatal cases reported
  2. Monitor blood pressure before and during therapy; less hypertension risk than venlafaxine but still monitor
  3. For pain indications, response should be reassessed at 8–12 weeks; adequate pain relief requires full therapeutic doses (60–120 mg)
  4. Counsel patients not to crush or open capsules — delayed-release coating prevents gastric degradation; if unable to swallow, capsules may be carefully opened and sprinkled on applesauce

Clinical Pearls

  • Duloxetine is one of only three FDA-approved drugs for fibromyalgia (with pregabalin and milnacipran) and is first-line for diabetic peripheral neuropathy pain
  • Unlike venlafaxine, duloxetine has balanced SERT:NET inhibition ratios even at low doses, meaning noradrenergic analgesia is present throughout the dose range

Safety Profile

Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required

Concordance Terms

Cross-referenced clinical concepts — click any term to see all content where it appears.

Antidepressant Chronic Musculoskeletal Pain Diabetic Peripheral Neuropathy Fibromyalgia Generalized Anxiety Disorder Major Depressive Disorder Stress Urinary Incontinence (international)
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