Brands, Medical Use, Clinical Data
Drug Category
Dosage Forms
Brands / Synonyms
Beta-phenylethylhydrazine; Fenelzina [Inn-Spanish]; Fenelzyna; Fenelzyne; Nardil; Phenalzine; Phenelezine; Phenelzinum [Inn-Latin]; Phenethylhydrazine; Phenylethyl hydrazine-HCl; Phenylethylhydrazine; Stinerval
Indications
For the treatment of depression.
Pharmacology
Phenelzine belongs to a class of antidepressants called monoamine oxidase inhibitors (MAOIs). Phenelzine works by irreversibly blocking the action of a chemical substance known as monoamine oxidase (MAO) in the nervous system. Within neurons, MAO appears to regulate the levels of monoamines released upon synaptic firing. Since depression is associated with low levels of monoamines, the inhibition of MAO serves to ease depressive symptoms.
Mechanism of Action
The irreversible inhibition of MAO by phenelzine causes an increase in the levels of serotonin, norepinephrine, and dopamine in the neuron, relieving depressive symptoms.
Absorption
Readily absorbed after oral administration.
Toxicity
Symptoms of overdose include drowsiness, dizziness, faintness, irritability, hyperactivity, agitation, severe headache, hallucinations, trismus, opisthotonos, convulsions and coma, rapid and irregular pulse, hypertension, hypotension and vascular collapse, precordial pain, respiratory depression and failure, hyperpyrexia, diaphoresis, and cool, clammy skin.
Biotrnasformation / Drug Metabolism
Hepatic. Acetylation of phenelzine appears to be a minor metabolic pathway. Beta-phenylethylamine is a metabolite of phenelzine, and there is indirect evidence that phenelzine may also be ring-hydroxylated and N-methylated.
Contraindications
Nardil should not be used in patients who are hypersensitive to the drug or its ingredients, with
pheochromocytoma, congestive heart failure, a history of liver disease, or abnormal liver function tests.
The potentiation of sympathomimetic substances and related compounds by MAO inhibitors may result in hypertensive
crises or related compounds (including methyldopa, L-dopa, L-tryptophan, L-tyrosine, and phenylalanine). Hypertensive
crises during Nardil therapy may also be caused by the ingestion of foods with a high concentration of tyramine or
dopamine. Therefore, patients being treated with Nardil should avoid high protein food that has undergone protein
breakdown by aging, fermentation, pickling, smoking, or bacterial contamination. Patients should also avoid cheeses
(especially aged varieties), pickled herring, beer, wine, liver, yeast extract (including brewer's yeast in large
quantities), dry sausage (including Genoa salami, hard salami, pepperoni, and Lebanon bologna), pods of broad beans
(fava beans), and yogurt. Excessive amounts of caffeine and chocolate may also cause hypertensive reactions.
Nardil should not be used in combination with dextromethorphan or with CNS depressants such as alcohol and certain
narcotics. Excitation, seizures, delirium, hyperpyrexia, circulatory collapse, coma, and death have been reported in
patients receiving MAOI therapy who have been given a single dose of meperidine. Nardil should not be administered
together with or in rapid succession to other MAO inhibitors because HYPERTENSIVE CRISES and convulsive seizures,
fever, marked sweating, excitation, delirium, tremor, coma, and circulatory collapse may occur.
A List of MAO Inhibitors by generic name follows:
pargyline hydrochloride
pargyline hydrochloride
and methylclothiazide
furazolidone
isocarboxazid
procarbazine
tranylcypromine
Nardil should also not be used in combination with buspirone HCl, since several cases of elevated blood pressure
have been reported in patients taking MAO inhibitors who were then given buspirone HCl. At least 10 days should
elapse between the discontinuation of Nardil and the institution of another antidepressant or buspirone HCl, or the
discontinuation of another MAO inhibitor and the institution of Nardil.
There have been reports of serious reactions (including hyperthermia, rigidity, myoclonic movements and death)
when serotoninergic drugs (e.g., dexfenfluramine, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine) have
been combined with an MAO inhibitor. Therefore the concomitant use of Nardil with serotoninergic agents is
contraindicated. Allow at least five weeks between discontinuation of fluoxetine and initiation of Nardil and at
least 10 days between discontinuation of Nardil and initiation of fluoxetine, or other serotoninergic agents. Before
initiating Nardil after using other serotoninergic agents, a sufficient amount of time must be allowed for clearance
of the serotoninergic agent and its active metabolites.
The combination of MAO inhibitors and tryptophan has been reported to cause behavioral and neurologic syndromes
including disorientation, confusion, amnesia, delirium, agitation, hypomanic signs, ataxia, myoclonus, hyperreflexia,
shivering, ocular oscillations, and Babinski signs.
The concurrent administration of an MAO inhibitor and bupropion hydrochloride (Wellbutrin®) is
contraindicated. At least 14 days should elapse between discontinuation of an MAO inhibitor and initiation of
treatment with bupropion hydrochloride.
Patients taking Nardil should not undergo elective surgery requiring general anesthesia. Also, they should not be
given cocaine or local anesthesia containing sympathomimetic vasoconstrictors. The possible combined hypotensive
effects of Nardil and spinal anesthesia should be kept in mind. Nardil should be discontinued at least 10 days prior
to elective surgery.
MAO inhibitors, including Nardil, are contraindicated in patients receiving guanethidine.
Drug Interactions
In patients receiving nonselective monoamine oxidase (MOA) inhibitors in combination with serotoninergic agents
(e.g., dexfenfluramine, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafexine) there have been reports of
serious, sometimes fatal, reactions. Because Nardil is a monoamine oxidase (MAO) inhibitor, Nardil should not be used
concomitantly with a serotoninergic agent.
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