PERTOFRANE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PERTOFRANE (PERTOFRANE).
Tricyclic antidepressant that inhibits the reuptake of norepinephrine and serotonin at the presynaptic neuronal membrane, increasing their concentrations in the synaptic cleft.
| Metabolism | Hepatic via CYP450 enzymes, primarily CYP2D6. |
| Excretion | Primarily renal (70%), with 30% as unchanged drug; remainder as glucuronide and sulfate conjugates. Biliary/fecal excretion accounts for <5%. |
| Half-life | Terminal elimination half-life is 14–21 hours. Steady-state is reached within 5–7 days. The half-life is prolonged in elderly and patients with hepatic impairment. |
| Protein binding | 94–96% bound, primarily to alpha-1-acid glycoprotein and albumin. |
| Volume of Distribution | Vd = 8–15 L/kg, indicating extensive tissue distribution and high lipophilicity. |
| Bioavailability | Oral bioavailability is 30–60% due to extensive first-pass metabolism. IM bioavailability is nearly 100% for desipramine (active metabolite). |
| Onset of Action | Oral: 2–3 weeks for antidepressant effect; immediate (minutes) for sedative effects. IM: 30–60 minutes for sedation. |
| Duration of Action | After single oral dose: 24–36 hours for antidepressant effect; sedative effect lasts 6–8 hours. Steady-state maintained with once-daily dosing. |
150-300 mg oral in divided doses per day; 75-150 mg IM in divided doses per day
| Dosage form | CAPSULE |
| Renal impairment | eGFR > 60 mL/min: No adjustment needed; eGFR 10-60 mL/min: Use with caution, reduce dose by 50%; eGFR < 10 mL/min: Not recommended due to accumulation |
| Liver impairment | Child-Pugh A: No adjustment; Child-Pugh B: Reduce dose by 50%; Child-Pugh C: Contraindicated |
| Pediatric use | Weight < 30 kg: 1 mg/kg/day oral in divided doses; Weight 30-50 kg: 2.5 mg/kg/day oral in divided doses; Not recommended under 6 years |
| Geriatric use | Initial dose 30-50 mg/day oral, increase slowly; maximum 150 mg/day; monitor for anticholinergic effects and cardiac toxicity |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PERTOFRANE (PERTOFRANE).
| Breastfeeding | Excreted into breast milk (M/P ratio not established). Limited data; potential for adverse effects in nursing infants (drowsiness, irritability). Use with caution, especially in neonates. |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no clear teratogenicity. Second and third trimesters: Risk of neonatal withdrawal symptoms (tachycardia, irritability, respiratory distress) if used near term. Avoid use unless benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
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 |
Hypersensitivity to desipramine or other tricyclics; recent myocardial infarction; concurrent use of MAOIs (within 14 days); use in patients with cardiac conduction abnormalities or arrhythmias.
| Precautions | Activation of mania/hypomania; seizures; angle-closure glaucoma; urinary retention; cardiovascular effects (QT prolongation, arrhythmias); serotonin syndrome when combined with other serotonergic drugs; anticholinergic effects. |
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| Monitor maternal heart rate, blood pressure, and ECG (risk of QT prolongation). In fetus: serial ultrasound for growth restriction. Neonatal assessment for withdrawal symptoms and cardiac effects. |
| Fertility Effects | May impair male and female fertility (e.g., reduced libido, erectile dysfunction, amenorrhea). Reversible upon discontinuation. |