PROCAPAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROCAPAN (PROCAPAN).
Procapan is a tricyclic antidepressant that inhibits the reuptake of norepinephrine and serotonin, increasing their concentrations in the synaptic cleft.
| Metabolism | Hepatic, primarily via CYP2D6 and CYP3A4; undergoes N-demethylation and hydroxylation. |
| Excretion | Renal: 70-80% unchanged; fecal: 10-20% as metabolites; biliary: <5% |
| Half-life | Terminal half-life: 6.5 hours (range 4-9 h) in normal renal function; prolonged in renal impairment (up to 15 h in ESRD) |
| Protein binding | 98% bound, primarily to alpha-1-acid glycoprotein and albumin |
| Volume of Distribution | Vd: 3.5 L/kg (range 2-5 L/kg), indicating extensive tissue distribution |
| Bioavailability | Oral: 50-60% (first-pass effect); IM: 70-80%; Sublingual: 40-50% |
| Onset of Action | IV: 1-2 minutes; IM: 10-20 minutes; Oral: 45-90 minutes |
| Duration of Action | IV: 30-60 minutes; IM: 2-4 hours; Oral: 4-6 hours (dose-dependent) |
Adults: 10 mg orally three times daily; maximum 40 mg/day.
| Dosage form | CAPSULE |
| Renal impairment | eGFR >30 mL/min: No adjustment. eGFR 15-30 mL/min: Reduce dose to 5 mg three times daily. eGFR <15 mL/min: Not recommended. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose to 5 mg three times daily. Child-Pugh C: Not recommended. |
| Pediatric use | Children <12 years: Not established. Children ≥12 years: 5 mg orally three times daily; maximum 20 mg/day. |
| Geriatric use | Initial dose: 5 mg orally three times daily; titrate cautiously due to renal and hepatic impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROCAPAN (PROCAPAN).
| Breastfeeding | Excreted in breast milk; M/P ratio not determined. Avoid breastfeeding due to potential for infant sedation and withdrawal. |
| Teratogenic Risk | FDA Pregnancy Category D. First trimester: associated with fetal malformations (neural tube defects, cardiovascular anomalies). Second trimester: increased risk of preterm labor. Third trimester: risk of neonatal withdrawal and respiratory depression. |
| Fetal Monitoring |
■ FDA Black Box Warning
Suicidality and antidepressant drugs: increased risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.
| Serious Effects |
["Concomitant MAO inhibitors","Recent myocardial infarction","Known hypersensitivity to tricyclic antidepressants","Severe hepatic impairment"]
| Precautions | ["Clinical worsening and suicide risk","Serotonin syndrome","Cardiovascular effects (QT prolongation, orthostatic hypotension)","Seizure threshold lowering","Angle-closure glaucoma","Urinary retention"] |
Loading safety data…
| Monitor maternal vital signs, fetal heart rate, and uterine activity. Perform serial ultrasound for fetal growth and anatomy. Assess neonatal for withdrawal symptoms after delivery. |
| Fertility Effects | May cause menstrual irregularities and anovulation. Discontinuation of therapy can restore fertility. |