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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VIVACTIL (VIVACTIL).
| Breastfeeding | Present in breast milk; M/P ratio 0.5–1.9. Cases of drowsiness and poor feeding in infants reported; avoid breastfeeding or use with caution. |
| 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 |
■ 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 protriptyline","Recent myocardial infarction","Concurrent MAOI therapy","QT prolongation or concomitant QT-prolonging drugs"]
| Precautions | ["Activation of mania/hypomania","Seizure threshold lowering","Cardiovascular toxicity (QT prolongation, arrhythmias)","Angle-closure glaucoma","Urinary retention","Hepatic impairment","Concomitant MAOI use"] |
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| 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. |