MAJOR — Use With Caution
DANGEROUS — potent CYP2D6 inhibition elevates doxepin
Evidence level: STRONG
Prozac dramatically increases doxepin levels, risking toxicity and serotonin syndrome.
Fluoxetine potently inhibits CYP2D6, increasing doxepin and its active metabolite nordoxepin levels. Dual serotonergic mechanism.
Generally avoid. If necessary, major dose reduction and monitoring required.
Take Fluoxetine at the same time each day — morning is most common to avoid sleep disruption. Doxepin follows its prescribed schedule. SSRIs have a long half-life, so consistency matters more than the exact hour.
Cardiac disease, elderly, CYP2D6 poor metabolizers
Cardiac arrhythmias, excessive sedation, anticholinergic toxicity, serotonin syndrome
Consider alternatives to this combination.
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 dramatically increases doxepin levels, risking toxicity and serotonin syndrome.
Take Fluoxetine at the same time each day — morning is most common to avoid sleep disruption. Doxepin follows its prescribed schedule. SSRIs have a long half-life, so consistency matters more than the exact hour.
Cardiac arrhythmias, excessive sedation, anticholinergic toxicity, serotonin syndrome
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.
Consider alternatives to this combination.
Or browse the full interaction database (121,000+ pairs).