Amitriptyline is a tricyclic antidepressant used for depression, neuropathic pain, migraine prophylaxis, and urinary incontinence.
Also known as: amitriptyline, laroxyl, tryptizol
CYP2D6 inhibitor SSRI + TCA: amitriptyline levels increased 2-4-fold. Risk of cardiac toxicity.
Fluoxetine inhibits CYP2D6, the main metabolic pathway for amitriptyline (N-demethylation). TCA levels may increase 2-4-fold, with risk of cardiac toxicity: QTc prolongation >500 ms, ventricular arrhythmias (torsades de pointes), seizures, and CNS depression. Amitriptyline has a narrow therapeutic index (toxic level: >250 ng/mL). Monitor ECG and TCA levels if co-administration is unavoidable. Reduce TCA dose by 50% and maintain low dose. Consider switching fluoxetine to an SSRI with less CYP2D6 inhibition (sertraline, citalopram).
CYP2D6 inhibitor SSRI + TCA: amitriptyline levels increased 2-4-fold. Risk of cardiac toxicity (QTc prolongation, arrhythmias).
Fluoxetine inhibits CYP2D6, the main metabolic pathway for amitriptyline. TCA levels may increase significantly, with risk of QTc prolongation, arrhythmias, and seizures.
ECG (QTc), TCA levels, signs of toxicity (dry mouth, urinary retention, confusion).
QTc >500 ms, arrhythmias, seizures.
Avoid combination if possible. If necessary, reduce TCA dose by 50% and monitor ECG and TCA levels.
DailyMed/FDA
No documented food or drink interactions.
No documented disease interactions.
No documented pregnancy or breastfeeding information.
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
TCA with noradrenergic and serotonergic activity. Strong anticholinergic effect.
Inhibits noradrenaline (NERT) and serotonin (SERT) reuptake. Anticholinergic (M1), antihistaminic (H1) and α1-adrenergic effects.
Oral absorption. Bioavailability: 30-60%. Peak: 2-8 h.
Metabolised by CYP2D6 and CYP3A4. Nortriptyline (active metabolite).
10-50 h (mean: 25 h).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
