MAJOR — Use With Caution
DANGEROUS — potent CYP2D6 inhibition elevates nortriptyline to toxic levels
Evidence level: STRONG
Prozac dramatically increases nortriptyline levels, risking cardiac toxicity and serotonin syndrome.
Fluoxetine potently inhibits CYP2D6, the primary enzyme metabolizing nortriptyline. Can increase nortriptyline levels 3-5x. Dual serotonergic risk.
Generally avoid. If unavoidable, reduce nortriptyline dose by 75% and monitor levels and ECG.
Take Fluoxetine at the same time each day — morning is most common to avoid sleep disruption. Nortriptyline 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, QT prolongation, seizures, serotonin syndrome
Requires ECG monitoring and TCA level checks. Consider alternatives.
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 nortriptyline levels, risking cardiac toxicity and serotonin syndrome.
Take Fluoxetine at the same time each day — morning is most common to avoid sleep disruption. Nortriptyline follows its prescribed schedule. SSRIs have a long half-life, so consistency matters more than the exact hour.
Cardiac arrhythmias, QT prolongation, seizures, 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.
Requires ECG monitoring and TCA level checks. Consider alternatives.
Or browse the full interaction database (121,000+ pairs).