PARNATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PARNATE (PARNATE).
Irreversible non-selective monoamine oxidase inhibitor (MAOI-A and MAOI-B); increases synaptic concentrations of serotonin, norepinephrine, and dopamine by inhibiting their oxidative deamination.
| Metabolism | Hepatic metabolism via multiple pathways including acetylation and oxidation; metabolites primarily excreted renally. |
| Excretion | Renal (90% as metabolites, <1% unchanged); fecal (minor). |
| Half-life | Terminal half-life approximately 2.5 hours; clinically, MAO inhibition persists for 2-3 weeks post discontinuation due to irreversible enzyme binding. |
| Protein binding | <10% bound to plasma proteins. |
| Volume of Distribution | Approximately 1.8 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral: approximately 70% (extensive first-pass metabolism). |
| Onset of Action | Oral: 2-3 weeks for antidepressant effect; inhibition of platelet MAO occurs within 24 hours. |
| Duration of Action | Antidepressant effect persists for 2-3 weeks after cessation due to irreversible MAO inhibition; enzyme regeneration required. |
10 mg orally twice daily; increase by 10 mg/day at 1-week intervals up to 60 mg/day; usual therapeutic range 30-60 mg/day in divided doses.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment recommended; use caution in severe renal impairment (CrCl <30 mL/min). |
| Liver impairment | Contraindicated in patients with hepatic impairment (Child-Pugh class A, B, or C); no dosing recommendation available. |
| Pediatric use | Not recommended for use in children under 18 years due to lack of safety and efficacy data. |
| Geriatric use | Initiate at the low end of the dosing range (10 mg/day); titrate slowly due to increased sensitivity; monitor for hypotension and drug interactions. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PARNATE (PARNATE).
| Breastfeeding | Tranylcypromine is excreted into breast milk. M/P ratio not reported. Due to potential for serious adverse reactions (e.g., MAO inhibition in infant), breastfeeding is not recommended during therapy. |
| Teratogenic Risk | PARNATE (tranylcypromine) is a non-selective MAO inhibitor. Data on human pregnancy are limited. Animal studies have shown no teratogenic effects. However, MAOIs in general should be used during pregnancy only if clearly needed. First trimester: potential risk unknown but theoretical concerns due to enzyme inhibition. Second and third trimesters: may cause fetal MAO inhibition and potential cardiovascular effects; risk of hypertensive crisis in mother. Overall, FDA Pregnancy Category C. |
■ FDA Black Box Warning
WARNING: In children, adolescents, and young adults, antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. PARNATE is not approved for use in pediatric patients.
| Serious Effects |
["Concomitant use of other MAOIs, SSRIs, SNRIs, tricyclic antidepressants, bupropion, or other serotonergic drugs","Pheochromocytoma","Cardiovascular disease (hypertension, cerebrovascular disease, coronary artery disease)","History of hypersensitivity to tranylcypromine","Use within 14 days of elective surgery requiring general anesthesia","Epinephrine or norepinephrine (local anesthetic use allowed with caution)"]
| Precautions | ["Hypertensive crisis: avoid tyramine-rich foods, sympathomimetic agents, and other drugs that increase blood pressure","Serotonin syndrome: avoid coadministration with serotonergic drugs, including SSRIs, SNRIs, triptans, and bupropion","Manic activation: may precipitate mania/hypomania in patients with bipolar disorder","Seizure threshold: may lower seizure threshold; caution in patients with epilepsy","Suicidal thoughts: monitor for worsening depression or suicidality","Discontinuation syndrome: taper gradually to avoid withdrawal symptoms"] |
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| Fetal Monitoring | Monitor maternal blood pressure frequently for hypertensive crises. Monitor for signs of serotonin syndrome. Fetal monitoring: consider fetal heart rate monitoring if maternal hypertension develops. Assess neonatal adaptation after delivery, including withdrawal or MAO inhibition effects. |
| Fertility Effects | No specific human data on fertility effects. Animal studies have not reported significant impairment. However, MAOIs may theoretically affect reproductive hormones via monoamine modulation. |