indication

For the treatment of major depressive disorder. Has also been used with some success in the management of bulimia nervosa.

pharmacology

Phenelzine belongs to a class of antidepressants called monoamine oxidase inhibitors (MAOIs). MAO is an enzyme that catalyzes the oxidative deamination of a number of amines, including serotonin, norepinephrine, epinephrine, and dopamine. Two isoforms of MAO, A and B, are found in the body. MAO-A is mainly found within cells located in the periphery and catalyzes the breakdown of serotonin, norepinephrine, epinephrine, dopamine and tyramine. MAO-B acts on phenylethylamine, norepinephrine, epinephrine, dopamine and tyramine, is localized extracellularly and is found predominantly in the brain. While the mechanism of MAOIs is still unclear, it is thought that they act by increasing free serotonin and norepinephrine concentrations and/or by altering the concentrations of other amines in the CNS. It has been postulated that depression is caused by low levels of serotonin and/or norepinephrine and that increasing serotonergic and norepinephrinergic neurotransmission results in relief of depressive symptoms. MAO A inhibition is thought to be more relevant to antidepressant activity than MAO B inhibition. Selective MAO B inhibitors, such as selegiline, have no antidepressant effects. Response to therapy generally occurs 2 - 4 weeks following onset though some patients may not experience symptom relief for up to 8 weeks.

mechanism of action

Although the exact mechanism of action has not been determined, it appears that the irreversible, nonselective inhibition of MAO by phenelzine relieves depressive symptoms by causing an increase in the levels of serotonin, norepinephrine, and dopamine in the neuron.

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. Hypertensive crisis may occur with the ingestion of tyramine-rich foods such as cured meats, poultry or fish, aged cheeses, concentrated soy products, tap beer and wine, yeast extracts, broad bean pods and fava beans and sauerkraut.

biotransformation

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.

absorption

Readily absorbed after oral administration.

half life

1.2-11.6 hours following single dose administration. Multiple-dose pharmacokinetics have not been studied.

route of elimination

NARDIL ® is extensively metabolized, primarily by oxidation via monoamine oxidase.

drug interactions

Almotriptan: The MAO inhibitor, phenelzine, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, almotriptan. Concomitant therapy is contraindicated.

Altretamine: Risk of severe hypotension

Amitriptyline: Possibility of severe adverse effects

Amoxapine: Possibility of severe adverse effects

Amphetamine: Possible hypertensive crisis

Atomoxetine: Possible severe adverse reaction with this combination

Benzphetamine: MAO Inhibitors may enhance the hypertensive effect of Amphetamines. Concomitant use of amphetamines and monoamine oxidase inhibitors (MAOI) should be avoided. If used concomitantly, careful monitoring of blood pressure must occur. It may take up to 2 weeks after the discontinuation of an MAOI for the effects to dissipate enough to afford safety to the administration of interacting agents.

Bezafibrate: MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid concomitant use of bezafibrate with monoamine oxidase inhibitors (MAOIs) like phenelzine.

Brimonidine: MAO Inhibitors like phenelzine may enhance the hypertensive effect of Alpha2-Agonists (Ophthalmic). The concomitant use of monoamine oxidase inhibitors and ophthalmic alpha2 agonists is contraindicated.

Buprenorphine: Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like phenelzine. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.

Bupropion: Possible severe adverse reaction with this combination

Buspirone: Possible blood pressure elevation

Citalopram: Possible severe adverse reaction with this combination

Clomipramine: Possibility of severe adverse effects

Desipramine: Possibility of severe adverse effects

Desvenlafaxine: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.

Dexfenfluramine: Possible hypertensive crisis

Dextroamphetamine: Possible hypertensive crisis

Dextromethorphan: Possible severe adverse reaction

Diethylpropion: Possible hypertensive crisis

Dobutamine: Increased arterial pressure

Donepezil: Possible antagonism of action

Dopamine: Increased arterial pressure

Doxepin: Possibility of severe adverse effects

Duloxetine: Possible severe adverse reaction with this combination

Entacapone: Possible hypertensive crisis with this combination

Ephedra: Increased arterial pressure

Ephedrine: Increased arterial pressure

Epinephrine: Increased arterial pressure

Escitalopram: Possible severe adverse reaction with this combination

Fenfluramine: Possible hypertensive crisis

Fenoterol: Increased arterial pressure

Fluoxetine: Possible severe adverse reaction with this combination

Fluvoxamine: Possible severe adverse reaction with this combination

Galantamine: Possible antagonism of action

Guanethidine: Phenelzine may decrease the effect of guanethidine.

Imipramine: Possibility of severe adverse effects

Isoproterenol: Increased arterial pressure

Levodopa: Possible hypertensive crisis

Mazindol: Possible hypertensive crisis

Meperidine: Potentially fatal adverse effects

Mephentermine: Increased arterial pressure

Metaraminol: Increased arterial pressure

Methamphetamine: Possible hypertensive crisis

Methotrimeprazine: Possible severe adverse reaction with this combination

Methoxamine: Increased arterial pressure

Methylphenidate: Possible hypertensive crisis with this combination

Midodrine: Possible hypertensive crisis with this combination

Mirtazapine: Possible severe adverse reaction with this combination

Naratriptan: The use of two serotonin modulators increases the risk of serotonin syndrome. Consider alternate therapy or monitor for signs and symptoms of serotonin syndrome.

Nefazodone: Possible severe adverse reaction with this combination

Norepinephrine: Increased arterial pressure

Nortriptyline: Possibility of severe adverse effects

Orciprenaline: Increased arterial pressure

Paroxetine: Possible severe adverse reaction with this combination

Phendimetrazine: Possible hypertensive crisis

Phentermine: Possible hypertensive crisis

Phenylephrine: Increased arterial pressure

Phenylpropanolamine: Increased arterial pressure

Pirbuterol: Increased arterial pressure

Procaterol: Increased arterial pressure

Protriptyline: Possibility of severe adverse effects

Pseudoephedrine: Increased arterial pressure

Rivastigmine: Possible antagonism of action

Rizatriptan: The MAO inhibitor, phenelzine, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, rizatriptan. Concomitant therapy is contraindicated.

Salbutamol: Increased arterial pressure

Sertraline: Possible severe adverse reaction with this combination

Sibutramine: Possible serotoninergic syndrome with this combination

Sumatriptan: The MAO inhibitor, phenelzine, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, sumatriptan. Concomitant therapy is contraindicated.

Tacrine: The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Phenelzine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.

Terbutaline: Increased arterial pressure

Tetrabenazine: Tetrabenazine may increase the adverse/toxic effects of Phenelzine. Concomitant therapy is contraindicated.

Tolcapone: Tolcapone and Phenelzine decrease the metabolism of endogenous catecholamines. Concomitant therapy may result in increased catecholamine effects. Consider alternate therapy or use cautiously and monitor for increased catecholamine effects.

Tramadol: Tramadol may increase the risk of serotonin syndrome and seizure induction by the MAO inhibitor, phenelzine.

Tranylcypromine: Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.

Trazodone: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Trimethobenzamide: Trimethobenzamide and Phenelzine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Trimipramine: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.

Triprolidine: Triprolidine and Phenelzine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.

Trospium: Trospium and Phenelzine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Tryptophanyl-5'amp: Possible severe adverse reaction with this combination

Venlafaxine: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.

Vilazodone: MAO Inhibitors may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome.

Zolmitriptan: The MAO inhibitor, phenelzine, may increase the serum concentration of zolmitriptan by decreasing its metabolism. Concomitant therapy and use of zolmitriptan within two weeks of discontinuing phenelzine are contraindicated.