NARDIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NARDIL (NARDIL).
Irreversible, non-selective monoamine oxidase inhibitor (MAOI) that increases synaptic concentrations of monoamines (norepinephrine, serotonin, dopamine) by inhibiting their oxidative deamination.
| Metabolism | Hepatic metabolism primarily via acetylation and oxidation. N-acetyltransferase 2 (NAT2) is a major enzyme; acetylation phenotype (slow vs. fast acetylators) affects drug levels and toxicity. |
| Excretion | Renal: 70–80% as metabolites and unchanged drug; biliary/fecal: 20–30%. |
| Half-life | Terminal elimination half-life is approximately 11–13 hours; due to irreversible MAO inhibition, clinical effects persist for 1–2 weeks after discontinuation. |
| Protein binding | Approximately 90% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Vd approximately 1.5 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 50% due to extensive first-pass metabolism. |
| Onset of Action | Oral: 2–4 weeks for antidepressant effect; peak plasma concentrations reached in 1–2 hours. |
| Duration of Action | Pharmacologic effect (MAO inhibition) persists up to 2 weeks after cessation; clinical antidepressant effect requires continued dosing. |
Initial: 15 mg orally three times daily; increase gradually to 45-60 mg/day in divided doses; maximum 90 mg/day.
| Dosage form | TABLET |
| Renal impairment | No specific guidelines; use with caution in renal impairment. Avoid in severe renal failure (CrCl <30 mL/min). |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). In mild to moderate impairment (Child-Pugh A or B), reduce dose by 50% and titrate cautiously. |
| Pediatric use | Not recommended for children under 16 years due to lack of safety and efficacy data. |
| Geriatric use | Initiate at lower doses (e.g., 15 mg/day) with slower titration; monitor for orthostatic hypotension, sedation, and anticholinergic effects. Maximum dose typically 60 mg/day. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NARDIL (NARDIL).
| Breastfeeding | No human data available; M/P ratio unknown. Nardil is excreted in milk in animal studies. Due to potential for serious adverse effects (e.g., hypertensive crisis, serotonin syndrome) in the nursing infant, breastfeeding is not recommended. |
| Teratogenic Risk | Pregnancy Category C. First trimester: limited human data; animal studies show increased fetal resorptions and skeletal abnormalities in rats at doses 1.5-3 times MRHD. Second and third trimesters: potential risk of neonatal withdrawal (irritability, jitteriness) if used near term; theoretical risk of pulmonary hypertension in the neonate. Avoid use unless benefit outweighs risk. |
■ FDA Black Box Warning
Increased risk of suicidal thoughts and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders. Balance this risk with clinical need. Close monitoring for worsening and emergence of suicidal ideation is required.
| Serious Effects |
["Hypertension requiring antihypertensives","Pheochromocytoma","Liver disease","Congestive heart failure","Concurrent use of other MAOIs or within 14 days","Concurrent use of SSRIs, SNRIs, TCAs, bupropion, linezolid, methylene blue, buspirone, dextromethorphan, meperidine, tramadol, methadone, and other serotonergic drugs","Tyramine-rich foods during therapy and for 2 weeks after discontinuation","Hypersensitivity to any component","Elective surgery requiring general anesthesia within 10 days"]
| Precautions | ["Hypertensive crisis with tyramine-rich foods or sympathomimetic drugs","Serotonin syndrome with serotonergic drugs (e.g., SSRIs, SNRIs, TCAs, meperidine, dextromethorphan)","Suicidal ideation risk","Hepatic toxicity; contraindicated in liver disease","Orthostatic hypotension","Seizure threshold lowering","Electroconvulsive therapy interactions","Bipolar screening prior to initiation","Renal impairment caution","Pregnancy and lactation: limited data"] |
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| Fetal Monitoring | Monitor maternal blood pressure and signs of hypertensive crisis (due to dietary tyramine interactions). Monitor for serotonin syndrome symptoms (hyperthermia, rigidity, myoclonus). Fetal monitoring: fetal heart rate and growth assessments if used in pregnancy; neonatal observation for withdrawal symptoms if used near term. |
| Fertility Effects | Animal studies: decreased fertility in male and female rats at doses 1-2 times MRHD (e.g., reduced sperm count, prolonged estrous cycles). Human data insufficient; hormonal changes from MAO inhibition may affect ovulation and sperm production. Discontinuation may be needed for conception planning. |