What are the contraindications for Duloxetine (Cymbalta)?

Duloxetine (Cymbalta) Contraindications

Duloxetine (Cymbalta) is absolutely contraindicated in patients taking MAOIs, those with uncontrolled narrow-angle glaucoma, severe renal impairment (CrCl <30 mL/min), and end-stage renal disease, and in pregnant or breastfeeding women. 1

Primary Contraindications

Absolute Contraindications

• Monoamine Oxidase Inhibitors (MAOIs)

  • Concurrent use with MAOIs or within 14 days of stopping an MAOI 1
  • At least 5 days should pass after stopping duloxetine before starting an MAOI 1
  • This includes both psychiatric MAOIs and other medications with MAOI activity (e.g., linezolid, intravenous methylene blue) 1

• Uncontrolled Narrow-Angle Glaucoma

  • Risk of acute angle-closure glaucoma 1

• Severe Renal Impairment

  • Creatinine clearance <30 mL/min 1, 2
  • End-stage renal disease (ESRD) 2
  • Exposures of duloxetine and its metabolites significantly increase in these patients 2

• Pregnancy and Breastfeeding

  • Contraindicated in women who are pregnant or actively trying to conceive 3
  • Not recommended for use in women who are nursing 3

Hepatic Impairment

• Avoid use in patients with chronic liver disease or cirrhosis 1
• Duloxetine is extensively metabolized in the liver, and impaired hepatic function can lead to increased drug exposure 4

Drug Interactions to Avoid

Serotonergic Drugs (Risk of Serotonin Syndrome)

• Triptans
• Tricyclic antidepressants
• Fentanyl
• Lithium
• Tramadol
• Tryptophan
• Buspirone
• Amphetamines
• St. John's Wort 1

Drugs Affecting Coagulation

• Increased risk of bleeding when used with:
  • Aspirin
  • NSAIDs
  • Warfarin
  • Other anticoagulants 1

CYP1A2 Inhibitors

• Strong CYP1A2 inhibitors (e.g., fluvoxamine) can increase duloxetine exposure by up to 460% 4
• Dose adjustment or alternative medication should be considered 4

Special Populations and Considerations

Elderly Patients

• Higher risk of falls and fractures 1
• May require lower starting doses due to potential decreased renal function 4

Patients with Seizure Disorders

• Use with caution due to potential lowering of seizure threshold 3

Patients with Cardiovascular Disease

• Monitor for increases in blood pressure and heart rate 1, 5
• Symptomatic orthostatic hypotension may occur 1

Monitoring and Management

Initial Assessment

• Evaluate renal and hepatic function before starting treatment 1, 2
• Screen for use of contraindicated medications, especially MAOIs 1
• Assess baseline blood pressure and heart rate 1

Ongoing Monitoring

• Monitor for signs of serotonin syndrome (mental status changes, autonomic instability, neuromuscular symptoms) 1
• Watch for increased bleeding risk, especially if on anticoagulants 1
• Monitor for severe skin reactions (e.g., Stevens-Johnson syndrome) 1

Discontinuation

• Never stop abruptly due to discontinuation syndrome 1
• Common discontinuation symptoms include dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, and hyperhidrosis 1
• Gradual dose reduction is recommended 1

By understanding these contraindications and taking appropriate precautions, healthcare providers can safely prescribe duloxetine to appropriate patients while minimizing adverse effects and drug interactions.