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. |
| Molecular Weight | 266.38 |
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 | Imipramine (active metabolite of desipramine) is not recommended in first trimester due to risk of fetal malformations, particularly cardiovascular defects, based on some epidemiological studies. |
| 2nd trimester | Use only if clearly needed; monitor for maternal and fetal effects. No specific teratogenic risk in second trimester, but data limited. |
| 3rd trimester | Neonatal withdrawal syndrome (irritability, hypertonia, tremors) and respiratory distress have been reported. Avoid use near term unless necessary. |
Clinical note
Comprehensive clinical and safety monograph for PERTOFRANE (PERTOFRANE).
| Placental transfer | Desipramine crosses the placenta; found in fetal plasma at levels approximately 50% of maternal plasma. Extensive placental transfer occurs. |
| Breastfeeding | Desipramine is excreted into breast milk in low amounts. Relative infant dose is estimated to be 1-3% of maternal weight-adjusted dose. Monitor infant for sedation, irritability, and feeding difficulties. Generally considered compatible with breastfeeding if used at the lowest effective dose. |
■ 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 any tricyclic antidepressantConcomitant use with MAOIs (risk of serotonin syndrome)Recent myocardial infarctionAcute angle-closure glaucoma
| 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. |
| Food/Dietary | Avoid consuming excessive amounts of caffeine or tyramine-rich foods (aged cheese, cured meats, fermented products) as they may potentiate hypertensive effects. Alcohol should be avoided due to additive CNS depression and increased sedation. Grapefruit juice may inhibit metabolism; limit intake. |
Loading safety data…
| Lactation Rating | L2 (Limited data - probably compatible) |
| 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 | 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. |
| Clinical Pearls | Desipramine (Pertofrane) has a faster onset of action than other tricyclic antidepressants due to its active metabolite. Monitor for anticholinergic effects, especially in elderly patients. Avoid concurrent use with MAOIs. Use with caution in patients with cardiovascular disease; monitor ECG for QT prolongation. Therapeutic drug monitoring can guide dosing: target plasma levels 150-300 ng/mL. |
| Patient Advice | Take exactly as prescribed; do not stop abruptly to avoid withdrawal symptoms like nausea, headache, and malaise. · May take up to 2-4 weeks for full antidepressant effect; do not miss doses. · Avoid alcohol and other CNS depressants as they may worsen drowsiness or dizziness. · Report any suicidal thoughts, worsening depression, or unusual changes in behavior immediately. · May cause dry mouth, constipation, blurred vision, or urinary retention; drink plenty of fluids and use sugar-free gum. · Rise slowly from sitting or lying positions to avoid dizziness or fainting. · Notify healthcare provider before taking any over-the-counter or prescription medications, especially MAOIs, decongestants, or antihistamines. · Avoid driving or operating heavy machinery until you know how the medication affects you. · Store at room temperature away from moisture and heat. |