TRANYLCYPROMINE SULFATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRANYLCYPROMINE SULFATE (TRANYLCYPROMINE SULFATE).
Irreversible inhibitor of monoamine oxidase (MAO-A and MAO-B), thereby increasing synaptic concentrations of monoamines (e.g., serotonin, norepinephrine, dopamine).
| Metabolism | Hepatic, primarily via CYP2A6, with minor contributions from CYP2C8, CYP2D6, CYP3A4; also undergoes acetylation. |
| Excretion | Renal excretion of metabolites (primarily as conjugates) accounts for approximately 90% of elimination, with less than 1% excreted unchanged in urine. Fecal excretion is minimal. |
| Half-life | The terminal elimination half-life is approximately 2 hours (range 1.5–3 hours). However, MAO inhibition persists for 7–14 days after discontinuation due to irreversible enzyme binding. |
| Protein binding | Approximately 90–94% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 1.5–2.5 L/kg, indicating extensive tissue distribution, including high uptake in the brain. |
| Bioavailability | Oral bioavailability is approximately 50% due to extensive first-pass metabolism. No parenteral formulations are available. |
| Onset of Action | Oral: Therapeutic antidepressant effects typically begin within 7–10 days. MAO inhibition occurs rapidly (within hours), but clinical response is delayed. |
| Duration of Action | MAO inhibition lasts for up to 10–14 days after the last dose due to irreversible enzyme inactivation. Antidepressant effects persist as long as treatment continues. |
Adults: 10 mg orally twice daily, increasing if necessary after 2 weeks to 30 mg/day in divided doses; maximum 60 mg/day.
| Dosage form | TABLET |
| Renal impairment | No specific guidelines; use with caution in severe renal impairment (eGFR <30 mL/min) due to potential accumulation; consider dose reduction. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). For mild to moderate impairment (Child-Pugh A or B), reduce initial dose to 5 mg orally twice daily and titrate slowly with close monitoring. |
| Pediatric use | Not recommended for use in children; safety and efficacy not established for depression. For other indications (e.g., ADHD) off-label, use lowest effective dose under specialist guidance; typical starting dose 0.5 mg/kg/day in divided doses, not to exceed adult doses. |
| Geriatric use | Initiate at 5 mg orally twice daily; increase slowly every 1-2 weeks due to increased sensitivity and risk of orthostatic hypotension. Maximum recommended dose 30 mg/day. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRANYLCYPROMINE SULFATE (TRANYLCYPROMINE SULFATE).
| Breastfeeding | Excreted into breast milk; M/P ratio not established. Limited data; avoid use due to potential for adverse effects (serotonin syndrome, gastrointestinal upset). If used, monitor infant for irritability, poor feeding, and weight gain. |
| Teratogenic Risk | First trimester: Limited human data; animal studies show increased risk of fetal malformations (cardiovascular, skeletal) at high doses. Second and third trimesters: Risk of prenatal growth restriction, neurobehavioral effects (serotonin reuptake inhibition exposure). Potential for neonatal withdrawal syndrome (irritability, tremors, feeding difficulties) with third-trimester exposure. Overall, classified as FDA Pregnancy Category C. |
■ FDA Black Box Warning
WARNING: TRANNYLCYPROMINE SULFATE IS A MONOAMINE OXIDASE INHIBITOR (MAOI). SERIOUS AND LIFE-THREATENING REACTIONS HAVE BEEN REPORTED IN PATIENTS RECEIVING CONCOMITANT MAOIs AND CERTAIN OTHER DRUGS (E.G., SSRIs, SNRIs, TCAs, SYMPATHOMIMETICS), OR INGESTING HIGH TYRAMINE FOODS/BEVERAGES. THESE REACTIONS INCLUDE HYPERTENSIVE CRISIS, SEROTONIN SYNDROME, AND HYPOTENSION. MONITOR FOR SYMPTOMS OF HYPERTENSIVE CRISIS AND SEROTONIN SYNDROME. DISCONTINUE IMMEDIATELY IF ELEVATED BLOOD PRESSURE OR SYMPTOMS OF SEROTONIN SYNDROME OCCUR. MUST OBSERVE A DRUG-FREE INTERVAL OF AT LEAST 14 DAYS WHEN SWITCHING TO OR FROM OTHER MAOIs, SSRIs, SNRIs, OR TCAs.
| Serious Effects |
["Concurrent use of other MAOIs, SSRIs, SNRIs, TCAs, or other serotonergic drugs (e.g., buspirone, St. John's wort) within 14 days","Concurrent use of sympathomimetic drugs (e.g., amphetamines, cocaine, ephedrine)","Concurrent use of certain opioids (e.g., meperidine, tramadol, methadone)","Pheochromocytoma","Hepatic or renal impairment (severe)","History of hypertension crisis or stroke","Known hypersensitivity to tranylcypromine"]
| Precautions | ["Hypertensive crisis: Avoid foods/drugs with high tyramine content; monitor blood pressure.","Serotonin syndrome: Risk with concurrent serotonergic drugs; discontinue if symptoms occur.","Suicidality: Monitor for worsening depression, suicidal thoughts/behaviors, especially early in treatment.","Withdrawal: Avoid abrupt discontinuation; taper gradually.","Seizures: Use cautiously in patients with seizure disorders.","Electroconvulsive therapy (ECT): Potential risks; avoid combination.","Hypotension: May cause orthostatic hypotension; monitor in elderly.","Tyramine restricted diet: Patients must adhere to a low-tyramine diet to prevent hypertensive crisis."] |
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| Fetal Monitoring | Maternal: Blood pressure, heart rate, hepatic function, mental status changes (hypertensive crisis, serotonin syndrome). Fetal: Serial growth ultrasounds (every 4 weeks) from 24 weeks; nonstress test or biophysical profile after 32 weeks. Monitor for neonatal withdrawal after delivery. |
| Fertility Effects | Animal studies: Impaired fertility (decreased implantation, spermatogenesis inhibition) at high doses. Human data: Limited; may cause menstrual irregularities and ovulatory dysfunction due to prolactin elevation. No specific long-term fertility studies in humans. |