PHENELZINE SULFATE
Clinical safety rating: safe
Animal studies have demonstrated safety
Irreversible inhibitor of monoamine oxidase (MAO), preventing oxidative deamination of biogenic amines (norepinephrine, serotonin, dopamine) thereby increasing their synaptic concentrations.
| Metabolism | Primarily hepatic metabolism via oxidation and acetylation; main enzyme: monoamine oxidase (self-inhibition). Metabolites are inactive and excreted renally. |
| Excretion | Primarily renal; approximately 70% of the dose is excreted in urine as metabolites and unchanged drug (<1%). Biliary/fecal elimination accounts for about 30%. |
| Half-life | Terminal elimination half-life is approximately 11-12 hours. However, due to irreversible inhibition of MAO, clinical effects persist for up to 2-3 weeks after discontinuation. |
| Protein binding | Approximately 90% bound; primarily to albumin. |
| Volume of Distribution | 1-2 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Well absorbed orally; estimated absolute bioavailability is 50-90% due to first-pass metabolism. |
| Onset of Action | Oral: 2-4 weeks for antidepressant effect; maximum benefit may require 6 weeks. |
| Duration of Action | Pharmacodynamic effects persist for 2-3 weeks after stopping due to irreversible MAO inhibition. The drug's half-life does not predict duration of action. |
Initial: 15 mg PO TID; increase by 15 mg every 2-4 days to 60-90 mg/day in divided doses; max 90 mg/day.
| Dosage form | TABLET |
| Renal impairment | CrCl <30 mL/min: contraindicated; CrCl 30-60 mL/min: reduce dose by 25-50% and extend dosing interval. |
| Liver impairment | Child-Pugh A: caution, start at 50% dose; Child-Pugh B: 25% of standard dose; Child-Pugh C: contraindicated. |
| Pediatric use | Not recommended for patients <16 years; contraindicated due to risk of hypertensive crisis and serotonin syndrome. |
| Geriatric use | Start at 7.5 mg PO daily; titrate slowly to 30-45 mg/day; monitor for orthostatic hypotension and drug interactions. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Tyramine-containing foods and serotonergic drugs can cause hypertensive crisis and serotonin syndrome Requires strict dietary restrictions to prevent hypertensive crisis.
| Breastfeeding | Phenelzine is excreted into breast milk in small amounts; the milk-to-plasma ratio (M/P) is not well established. Due to potential for serious adverse effects in the infant, including inhibition of monoamine oxidase and hypertensive crisis, breastfeeding is generally not recommended. If used, monitor infant for irritability, poor feeding, and somnolence. |
| Teratogenic Risk | Phenelzine is a monoamine oxidase inhibitor (MAOI) with limited human data. Animal studies suggest adverse effects at high doses. In first trimester, fetal malformations are not clearly documented; however, MAO inhibition may affect fetal development. Second and third trimester exposure may be associated with fetal growth restriction, preterm birth, and transient neonatal symptoms including irritability, tremors, and respiratory depression. Risk cannot be excluded; use only if benefit outweighs risk. |
■ FDA Black Box Warning
Due to risk of serotonin syndrome, hypertensive crisis, and suicidal thoughts/behaviors. MAOIs should not be used in combination with serotonergic drugs or within 14 days of their discontinuation.
| Common Effects | Orthostatic hypotension |
| Serious Effects |
Absolute: Concurrent use with other MAOIs, SSRIs, SNRIs, triptans, bupropion, meperidine, tramadol, or buspirone. Pheochromocytoma. Severe hepatic impairment. Uncontrolled hypertension. Relative: Cardiovascular disease, history of stroke, epilepsy, hyperthyroidism, advanced age.
| Precautions | Risk of hypertensive crisis with tyramine-rich foods (cheese, wine, pickled foods); avoid concomitant use of sympathomimetics. Risk of serotonin syndrome with SSRIs, SNRIs, triptans. Use with caution in cardiovascular disease, epilepsy, hyperthyroidism, and hepatic impairment. Monitor for hypomania/mania in bipolar patients. Do not use within 14 days of other MAOIs or serotonergic drugs. |
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| Fetal Monitoring | Regular monitoring of maternal blood pressure (for hypertensive crises), liver function tests, and mental status. Fetal monitoring includes serial growth ultrasound for detection of growth restriction and fetal heart rate monitoring in later pregnancy. Neonatal monitoring for withdrawal symptoms or adverse effects after delivery. |
| Fertility Effects | Phenelzine may affect fertility in both males and females through inhibition of monoamine oxidase, potentially altering hormonal regulation. In females, hyperprolactinemia and menstrual irregularities are reported. In males, ejaculatory dysfunction and decreased libido may occur. Impact on fertility is reversible upon discontinuation. |