MODERATE — Monitor Closely
🟡 USE CAUTION — Fluoxetine and Hydrocodone may interact. Talk to your doctor before combining.
Evidence level: STRONG
Prozac blocks the enzyme that activates Vicodin. Your pain medication may not work as well.
Fluoxetine potently inhibits CYP2D6 which converts hydrocodone to hydromorphone (active metabolite). Reduces pain relief.
Fluoxetine can affect how your body processes Hydrocodone. Your doctor may need to monitor drug levels or adjust doses of Hydrocodone while you're also taking Fluoxetine.
Some opioids (tramadol, fentanyl, meperidine) have serotonergic activity and can cause serotonin syndrome with SSRIs. Take each at their prescribed times. Watch for agitation, rapid heartbeat, muscle rigidity, or confusion. Codeine and morphine are generally lower risk.
Higher risk with: liver impairment, genetic CYP enzyme variations (poor or ultra-rapid metabolizers), older age, polypharmacy (many medications).
Watch for signs of altered drug metabolism: either increased side effects (drug levels too high) or decreased effectiveness (drug levels too low). Report any changes to your doctor.
Mention this combination at your next appointment. Ask: "Should I adjust timing or doses of Fluoxetine and Hydrocodone?" Your doctor may want to monitor specific lab values.
Discuss this combination with your prescriber. They may adjust timing, dosing, or switch to an alternative with fewer interaction risks. Never stop an antidepressant abruptly — taper under medical guidance.
Prozac blocks the enzyme that activates Vicodin. Your pain medication may not work as well.
Some opioids (tramadol, fentanyl, meperidine) have serotonergic activity and can cause serotonin syndrome with SSRIs. Take each at their prescribed times. Watch for agitation, rapid heartbeat, muscle rigidity, or confusion. Codeine and morphine are generally lower risk.
Watch for signs of altered drug metabolism: either increased side effects (drug levels too high) or decreased effectiveness (drug levels too low). Report any changes to your doctor.
Discuss this combination with your prescriber. They may adjust timing, dosing, or switch to an alternative with fewer interaction risks. Never stop an antidepressant abruptly — taper under medical guidance.
Mention this combination at your next appointment. Ask: "Should I adjust timing or doses of Fluoxetine and Hydrocodone?" Your doctor may want to monitor specific lab values.
Or browse the full interaction database (121,000+ pairs).