Contraindications to Starting Duloxetine
Do not initiate duloxetine in patients taking MAOIs (including linezolid or IV methylene blue), those with substantial alcohol use, chronic liver disease/cirrhosis, or severe renal impairment (GFR <30 mL/min). 1
Absolute Contraindications
MAOI Use (Most Critical)
- Concurrent use with MAOIs intended to treat psychiatric disorders is absolutely contraindicated due to serotonin syndrome risk 1
- Timing requirements:
- Wait at least 14 days after stopping an MAOI before starting duloxetine
- Wait at least 5 days after stopping duloxetine before starting an MAOI 1
- Linezolid or IV methylene blue: Do not start duloxetine in patients receiving these medications (also MAOIs) 1
Hepatic Impairment
- Avoid in patients with chronic liver disease or cirrhosis 1
- Avoid in patients with substantial alcohol use - duloxetine and alcohol may interact to cause liver injury or aggravate pre-existing liver disease 1
Severe Renal Impairment
Important Clinical Caveats
Cardiovascular Considerations
While not absolute contraindications, exercise caution in:
- Patients with uncontrolled hypertension (duloxetine can cause mild BP increases) 2
- Patients at high risk for falls - duloxetine increases orthostatic hypotension risk, particularly in elderly patients, those on antihypertensives, or those taking potent CYP1A2 inhibitors 1
Drug Interactions Requiring Avoidance
- Strong CYP1A2 inhibitors (especially fluvoxamine): Can increase duloxetine exposure by 460%, creating risk of toxicity 3, 4
- Concomitant use should be avoided or duloxetine dose reduced if unavoidable
Bleeding Risk Situations
While not contraindications, be aware that duloxetine increases bleeding risk when combined with:
- NSAIDs, aspirin, warfarin, or other anticoagulants 1
- Consider alternative therapy in patients with active bleeding disorders or recent major surgery
Key Prescribing Points
The FDA label is explicit: these are the only true contraindications requiring complete avoidance 1. Other conditions warrant caution and monitoring but do not prohibit use. The MAOI contraindication is the most dangerous - serotonin syndrome can be life-threatening and develops rapidly with this combination 1.