phenelzine sulfate
Nardil

Available forms
Available by prescription only
Tablets: 15 mg

Indications and dosages
 Severe depression. Adults: 15 mg P.O. t.i.d. Increase rapidly to 60 mg daily; maximum daily dose is 90 mg. Onset of maximum therapeutic effect is 2 to 6 weeks. Some clinicians reduce dosage after response occurs; maintenance dose may be as low as 15 mg daily or every other day.

Pharmacodynamics
Antidepressant action: Depression is thought to result from low CNS levels of neurotransmitters, including norepinephrine and serotonin. Phenelzine inhibits MAO, an enzyme that normally inactivates amine-containing substances, thus increasing the level and activity of these substances.

Pharmacokinetics
Absorption: Absorbed rapidly and completely from GI tract.
Distribution: No information available.
Metabolism: Metabolized in liver.
Excretion: Excreted primarily in urine within 24 hours; some drug excreted in feces via biliary tract. Relatively short half-life, but enzyme inhibition is prolonged and unrelated to half-life.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in those with heart failure, pheochromocytoma, hypertension, liver disease, or CV disease. Also contraindicated during therapy with other MAO inhibitors (isocarboxazid, tranylcypromine); within 14 days of such therapy or within 14 days of elective surgery requiring general anesthesia; with cocaine use; or with local anesthesia containing sympathomimetic vasoconstrictors. Contraindicated within 2 weeks of selective serotonin reuptake inhibitor antidepressant use. Contraindicated by some manufacturers in patients older than age 60 because of possibility of existing cerebrosclerosis with damaged vessels.
  Use cautiously in patients at risk for diabetes, suicide, or seizure disorders and in those receiving thiazide diuretics or spinal anesthetics.

Interactions
Drug-drug. Amphetamines, ephedrine, phenylephrine, other related drugs: Enhances pressor effects. Avoid use together.
Barbiturates, dextromethorphan, narcotics, tricyclic antidepressants, other sedatives: Increases adverse reactions. Use cautiously and reduce dosage of phenelzine.
Disulfiram: May cause tachycardia, flushing, or palpitations. Monitor patient closely.
General, spinal anesthetics: Causes severe hypotension and excessive CNS depression. Avoid use together.
Local anesthetics (lidocaine, procaine): Decreases effectiveness of these drugs; causes poor nerve block. Stop phenelzine for at least 1 week before giving these drugs.
OTC cold, hay fever, weight-reduction products: Causes serious CV toxicity. Avoid use together.
Serotonergic drugs (fluoxetine, fluvoxamine, paroxetine, sertraline), tricyclic antidepressants: Causes serious adverse effects. At least a 2-week waiting period between drug use is recommended.
Drug-herb. Brewer’s yeast: Increases blood pressure. Discourage use together.
Cacao: Potentiates vasopressor effects. Discourage use together.
Cola nut: Large quantities can precipitate hypertensive crisis. Discourage use together.
Ephedra: May cause severe reactions, including hypertensive crisis. Discourage use together.
Ginseng: May cause adverse reactions, including headache, tremors, mania, insomnia, irritability, visual hallucinations. Discourage use together.
Yohimbe: Causes additive adverse effects. Avoid use together.
Drug-food. Foods high in caffeine, tryptophan, tyramine: May precipitate hypertensive crisis. Discourage use together.
Drug-lifestyle. Alcohol use: Increases adverse reactions. Discourage alcohol use or reduce dosage.

Adverse reactions
CNS: dizziness, vertigo, headache, hyperreflexia, tremor, muscle twitching, insomnia, drowsiness, weakness, fatigue.
CV: orthostatic hypotension, edema.
GI: dry mouth, anorexia, nausea, constipation.
GU: elevated urinary catecholamine levels, sexual disturbances.
Metabolic: weight gain.
Skin: diaphoresis.

Effects on lab test results
• May increase ALT and AST levels.
• May increase WBC count.

Overdose and treatment
Signs and symptoms of toxicity become apparent slowly (within 24 to 48 hours) and may last for up to 2 weeks. Agitation, flushing, tachycardia, hypotension, hypertension, palpitations, increased motor activity, twitching, increased deep tendon reflexes, seizures, hyperpyrexia, cardiorespiratory arrest, and coma may occur. Doses of 375 mg to 1.5 g have been ingested with fatal and nonfatal results.
 Give 5 to 10 mg phentolamine I.V. push for hypertensive crisis; treat seizures, agitation, or tremors with I.V. diazepam; tachycardia with beta blockers; and fever with cooling blankets. Monitor vital signs and fluid and electrolyte balance. Use of sympathomimetics (such as norepinephrine or phenylephrine) is contraindicated in hypotension caused by MAO inhibitors.

Special considerations
• Exercise precautions for use of MAO inhibitors, given alone or with other drugs, for 14 days after stopping drug.
• Consider inherent risk of suicide until significant improvement of depressive state occurs. High-risk patients should have close supervision during initial therapy. To reduce risk of suicidal overdose, prescribe smallest quantity of tablets consistent with good management.
• At start of therapy, patient should lie down for 1 hour after taking phenelzine; to prevent dizziness from orthostatic blood pressure changes, sudden changes to standing position should be avoided.
• Unlike therapy with other MAO inhibitors, therapy with phenelzine and tricyclic antidepressants is generally well tolerated.
Pediatric patients
• Drug isn’t recommended for children younger than age 16.
Geriatric patients
• Drug isn’t recommended for patients older than age 60.

Patient education
• Warn patient not to take alcohol, other CNS depressants, or OTC products (such as cold, hay fever, or diet preparations) without medical approval.
• Explain that many foods and beverages (such as wine, beer, cheeses, preserved fruits, meats, and vegetables) may interact with drug. A list of foods to avoid can usually be obtained from the dietary department or pharmacy at most hospitals.
• Tell patient to avoid hazardous activities that require alertness until drug’s full CNS effects are known. Suggest taking drug at bedtime to minimize daytime sedation.
• Instruct patient to take drug exactly as prescribed and not to double the dose if one is missed.
• Tell patient not to stop drug abruptly and to report any problems; dosage reduction can relieve most adverse reactions.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use