VIVACTIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VIVACTIL (VIVACTIL).
Norepinephrine and serotonin reuptake inhibitor; also has anticholinergic and antihistaminergic activity.
| Metabolism | Primarily hepatic via CYP2D6 and other microsomal enzymes; active metabolite desmethylprotriptyline. |
| Excretion | Primarily renal (approximately 70% as metabolites, <5% unchanged), with the remainder via fecal/biliary elimination. |
| Half-life | Terminal elimination half-life ranges 18–34 hours (mean ~25 hours); clinical steady-state achieved within 5–7 days. |
| Protein binding | Approximately 90% bound, primarily to albumin and α1-acid glycoprotein. |
| Volume of Distribution | Vd approximately 8–15 L/kg, indicating extensive tissue distribution with higher CNS concentration than plasma. |
| Bioavailability | Oral bioavailability approximately 30–40% due to first-pass metabolism (extensive hepatic cytochrome P450 biotransformation). |
| Onset of Action | Oral: 2–4 weeks for antidepressant effect (therapeutic lag); 1–2 weeks for sedation/anxiety relief. |
| Duration of Action | Antidepressant effect sustained 24–48 hours after last dose; elimination half-life supports once-daily dosing. Rebound effects unlikely due to long t½. |
| Molecular Weight | 310.86 |
10 mg orally twice daily (morning and afternoon) or 10 mg once daily at bedtime; may increase gradually to 60 mg/day in divided doses.
| Dosage form | TABLET |
| Renal impairment | For GFR <10 mL/min: use with caution and consider 50% dose reduction; no specific guidelines for GFR 10-50 mL/min. |
| Liver impairment | Child-Pugh class B or C: reduce dose by 50-75%; avoid use in severe hepatic impairment. |
| Pediatric use | Not recommended for children <12 years; for adolescents 12-18 years: 5-10 mg orally twice daily, max 60 mg/day. |
| Geriatric use | Initiate at 5 mg orally twice daily; increase slowly with monitoring for orthostatic hypotension and anticholinergic effects. |
| 1st trimester | Avoid; limited human data, animal studies show risk, possible fetal malformations. |
| 2nd trimester | Avoid; risk of fetal tachycardia, irritability, and withdrawal. |
| 3rd trimester | Avoid; risk of neonatal withdrawal, respiratory distress, and jitteriness. |
Clinical note
Comprehensive clinical and safety monograph for VIVACTIL (VIVACTIL).
| Placental transfer | Crosses placenta; present in cord blood and amniotic fluid. |
| Breastfeeding | Excreted into breast milk; case reports of drowsiness and poor feeding in infants. Use only if clearly needed. |
| Lactation Rating | L4 |
■ FDA Black Box Warning
Increased risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.
| Serious Effects |
Hypersensitivity to protriptylineRecent myocardial infarctionConcomitant MAO inhibitors use (within 14 days)Narrow-angle glaucomaUrinary retentionPropensity for urinary retention or obstructive uropathy
| Precautions | Activation of mania/hypomania, Seizure threshold lowering, Cardiovascular toxicity (QT prolongation, arrhythmias), Angle-closure glaucoma, Urinary retention, Hepatic impairment, Concomitant MAOI use |
| Food/Dietary | Avoid tyramine-rich foods (aged cheeses, cured meats, fermented products, soy sauce) if taking with MAOIs; however, protriptyline alone has no significant tyramine interaction. Grapefruit juice may increase protriptyline levels; avoid high intake. Alcohol can potentiate CNS depression. High-fiber foods may slightly reduce absorption; take at same time each day. |
Loading safety data…
| Teratogenic Risk | First trimester: Limited data; possible association with cardiovascular malformations. Second trimester: No specific malformations reported. Third trimester: Risk of neonatal withdrawal, respiratory distress, tachycardia, and hyperirritability if used near term. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, ECG for QT prolongation, serum drug levels if toxicity suspected; fetal ultrasound for growth and anomalies. |
| Fertility Effects | May cause menstrual irregularities, anovulation, and decreased libido; reversible on discontinuation. |
| Clinical Pearls | VIVACTIL (protriptyline) is a tricyclic antidepressant with a more activating profile; it has the fastest onset of weight gain among TCAs. It is often used for ADHD, narcolepsy, and depression with psychomotor retardation. Due to its long half-life (54-92 hours), dosing should be conservative in elderly. It has a high anticholinergic burden, risking urinary retention and cognitive impairment in older adults. Avoid in patients with recent MI or arrhythmias. Monitor EKG and drug levels in suspected overdose. |
| Patient Advice | Take exactly as prescribed; do not stop suddenly as withdrawal may occur. · May cause drowsiness or dizziness; avoid driving until you know how it affects you. · Avoid alcohol and other CNS depressants. · Report any suicidal thoughts or worsening depression immediately. · May cause dry mouth, constipation, blurred vision; use sugarless candy or gum for dry mouth. · Rise slowly from sitting or lying to prevent dizziness. · Do not take with MAOIs or within 14 days of stopping them. · Notify doctor if you experience fast/irregular heartbeat, difficulty urinating, or seizures. |