AVENTYL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AVENTYL (AVENTYL).
Nortriptyline, the active ingredient, inhibits the reuptake of norepinephrine and serotonin in the central nervous system, potentiating their effects. It also has anticholinergic and antihistaminergic properties.
| Metabolism | Extensively metabolized in the liver by cytochrome P450 enzymes (CYP2D6, CYP1A2, CYP2C19) via hydroxylation, N-demethylation, and N-oxidation; active metabolite: 10-hydroxynortriptyline. Metabolites are conjugated and excreted in urine. |
| Excretion | Renal (30% as unchanged drug and metabolites); biliary/fecal (70% as metabolites) |
| Half-life | Terminal elimination half-life: 19-24 hours; requires 4-6 days to reach steady state. |
| Protein binding | 90-95% bound primarily to albumin. |
| Volume of Distribution | 15-30 L/kg; indicates extensive tissue penetration. |
| Bioavailability | Oral: 30-60% due to first-pass metabolism. |
| Onset of Action | Oral: 2-3 hours for therapeutic effect; initial effects may be seen within 1 week. |
| Duration of Action | Duration of action after single oral dose: 24-48 hours; clinical effects persist for weeks. |
Adults: 25 mg orally 3 to 4 times daily, maximum 150 mg/day.
| Dosage form | SOLUTION |
| Renal impairment | GFR 10-50 mL/min: administer 50-75% of normal dose; GFR <10 mL/min: administer 50% of normal dose or every 12 hours. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated or reduce dose by 75% with monitoring. |
| Pediatric use | Children 6-12 years: 10-30 mg/day in divided doses; >12 years: 25-50 mg/day in divided doses, maximum 100 mg/day. Weight-based: 1-2 mg/kg/day. |
| Geriatric use | Initial dose 10-25 mg/day in divided doses, titrate slowly to maximum 100 mg/day; use with caution due to anticholinergic effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AVENTYL (AVENTYL).
| Breastfeeding | Excreted in human milk; M/P ratio unknown. Limited data suggests low levels; use with caution, monitor infant for sedation and anticholinergic effects. |
| Teratogenic Risk | First trimester: Limited human data, animal studies show no consistent teratogenicity; avoid due to risk of fetal tachycardia. Second/third trimester: Risk of neonatal withdrawal (irritability, feeding disorders) and anticholinergic effects (ileus, tachycardia). |
| Fetal Monitoring |
■ FDA Black Box Warning
Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders. Nortriptyline is not approved for use in pediatric patients.
| Serious Effects |
["Hypersensitivity to nortriptyline or any component of the formulation.","Concomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing an MAOI.","Acute recovery phase after myocardial infarction.","Concomitant use with cisapride, due to risk of QT prolongation."]
| Precautions | ["Suicidality: Monitor for worsening depression and suicidal thoughts, especially in young adults.","Cardiotoxicity: Risk of QT prolongation, arrhythmias, and sudden death; use with caution in patients with cardiovascular disease.","Serotonin syndrome: Risk when used with other serotonergic drugs.","Anticholinergic effects: Use caution in patients with prostatic hypertrophy, narrow-angle glaucoma, or urinary retention.","Seizures: May lower seizure threshold.","Electroconvulsive therapy (ECT): Avoid concomitant use.","Hepatic impairment: Use with caution; metabolism may be reduced.","Hyperthyroidism: May potentiate cardiac toxicity."] |
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| Maternal: ECG for QTc prolongation, blood pressure, liver function tests. Fetal/neonatal: Heart rate monitoring, observation for withdrawal or anticholinergic toxicity. |
| Fertility Effects | May cause sexual dysfunction (ejaculatory delay, decreased libido) in both sexes; animal studies show no direct effect on fertility. |
| Food/Dietary |
| Avoid tyramine-rich foods (aged cheeses, cured meats, sauerkraut, soy products, tap beers) as concomitant use with MAOIs is contraindicated. However, nortriptyline itself has minimal tyramine interaction. Grapefruit juice may increase nortriptyline levels; avoid or limit intake. High-fiber foods may reduce absorption; take with a full glass of water. |
| Clinical Pearls | Aventyl (nortriptyline) is a secondary amine tricyclic antidepressant with less anticholinergic and sedative effects than tertiary amines like amitriptyline. It exhibits a narrow therapeutic window; therapeutic plasma levels are 50-150 ng/mL. Use with caution in patients with cardiovascular disease due to risk of QT prolongation. Avoid abrupt discontinuation to prevent withdrawal-like symptoms. Monitoring of plasma levels is recommended in elderly and those with hepatic impairment. |
| Patient Advice | Take exactly as prescribed; do not adjust dose without consulting your doctor. · May cause drowsiness or dizziness; avoid driving until you know how it affects you. · Avoid alcohol and other CNS depressants. · Report any signs of serotonin syndrome (agitation, hallucinations, fever) or suicidal thoughts. · May take 2-4 weeks to see full therapeutic effect. · Do not stop abruptly; taper under medical supervision to avoid withdrawal symptoms. · Store at room temperature away from moisture and light. |