Does Codeine Sulfate Interact with Ketoconazole?
Codeine Sulfate and Ketoconazole have a major drug interaction according to U.S. FDA drug labeling data. Azole antifungal CYP3A4 inhibitor that increases codeine and morphine levels, potentially causing fatal respiratory depression. The mechanism involves inhibition of cyp3a4, increasing codeine metabolism to morphine via cyp2d6. Patients taking both medications should consult their healthcare provider before starting, stopping, or changing the dosage of either drug. This information is based on official FDA drug labeling sourced from OpenFDA and the NIH National Library of Medicine.
- Severity
- Major
- Ketoconazole Class
- Azole Antifungal
- Management
- Close medical supervision required
- Data Source
- U.S. FDA via OpenFDA
How This Interaction Works
The interaction between Codeine Sulfate and Ketoconazole occurs because inhibition of cyp3a4, increasing codeine metabolism to morphine via cyp2d6. Clinically, this means azole antifungal cyp3a4 inhibitor that increases codeine and morphine levels, potentially causing fatal respiratory depression. This is classified as a major interaction, meaning it could cause serious harm if not properly managed. Your healthcare provider may need to adjust dosages, substitute one medication, or increase monitoring frequency.
What To Tell Your Doctor or Pharmacist
If you are taking Codeine Sulfate and your doctor is considering prescribing Ketoconazole (or vice versa), make sure to:
- Inform your doctor and pharmacist of all current medications, including over-the-counter drugs and supplements
- Ask whether the benefits of combining these medications outweigh the risks for your specific situation
- Ask what symptoms to watch for that would indicate the interaction is causing problems
- Ask how frequently you should be monitored while these are co-prescribed
- Ask whether any dosage adjustments are needed
- Never stop or change either medication without first consulting your healthcare provider