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Home / Drugs / Starting with T / Tranylcypromine
 
Tranylcypromine
 

A propylamine formed from the cyclization of the side chain of amphetamine. This monoamine oxidase inhibitor is effective in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in panic and phobic disorders. (From AMA Drug Evaluations Annual, 1994, p311)
BrandsDl-Tranylcypromine
Parnate
Transamine
CategoriesAntidepressants
Anti-anxiety Agents
Antidepressive Agents
Monoamine Oxidase Inhibitors
ManufacturersGlaxosmithkline
Par pharmaceutical inc
PackagersGlaxoSmithKline Inc.
Kaiser Foundation Hospital
Kali Laboratories Inc.
Par Pharmaceuticals
Physicians Total Care Inc.

indication

For the treatment of major depressive episode without melancholia.

pharmacology

Tranylcypromine belongs to a class of antidepressants called monoamine oxidase inhibitors (MAOIs). Tranylcypromine is a non-hydrazine monoamine oxidase inhibitor with a rapid onset of activity. 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.

mechanism of action

Tranylcypromine irreversibly and nonselectively inhibits monoamine oxidase (MAO). 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, as this results in an increase in the concentrations of these amines within the CNS.

toxicity

In overdosage, some patients exhibit insomnia, restlessness and anxiety, progressing in severe cases to agitation, mental confusion and incoherence. Hypotension, dizziness, weakness and drowsiness may occur, progressing in severe cases to extreme dizziness and shock. A few patients have displayed hypertension with severe headache and other symptoms. Rare instances have been reported in which hypertension was accompanied by twitching or myoclonic fibrillation of skeletal muscles with hyperpyrexia, sometimes progressing to generalized rigidity and coma.

biotransformation

Hepatic.

absorption

Interindividual variability in absorption. May be biphasic in some individuals. Peak plasma concentrations occur in one hour following oral administration with a secondary peak occurring within 2-3 hours. Biphasic absorption may represent different rates of absorption of the stereoisomers of the drug, though additional studies are required to confirm this.

half life

1.5-3.2 hours in patients with normal renal and hepatic function

drug interactions

Alfentanil: Possible increased risk of serotonin syndrome.

Almotriptan: The MAO inhibitor, Tranylcypromine, may reduce the metabolism and clearance of the serotonin 5-HT1D receptor agonist, Almotriptan. Risk of serotonin syndrome and Almotriptan toxicity. Concomitant therapy should be avoided.

Amitriptyline: Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.

Amoxapine: Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.

Apraclonidine: The MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of the alpha2-agonist, Apraclonidine. Concomitant therapy is contraindicated.

Atomoxetine: The MAO inhibitor, Tranylcypromine, may increase the central neurotoxic effects of the Atomoxetine. These agents should not be administered within 14 days of each other.

Benzphetamine: The MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of the amphetamine, Benzphetamine. Concomitant therapy should be avoided.

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

Brimonidine: The MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of the alpha2-agonist, Brimonidine. Concomitant therapy is contraindicated.

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

Buprenorphine: Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like tranylcypromine. 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: The MAO inhibitor, Tranylcypromine, may increase the central neurotoxic effects of the Bupropion. These agents should not be administered within 14 days of each other.

Buspirone: Buspirone may increase the adverse effects of Tranylcypromine. Elevation of blood pressure may occur. Concomitant therapy also may increase the risk of serotonin syndrome. Concomitant therapy should be avoided.

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

Citalopram: Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.

Clomipramine: Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.

Cyclobenzaprine: Increased risk of serotonin syndrome. Concomitant use should be avoided. These agents should not be administered within 14 days of each other.

Desipramine: Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.

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

Dexfenfluramine: Possible hypertensive crisis

Dexmedetomidine: Tranylcypromine, a strong CYP2A6 inhibitor, may decrease the metabolism and clearance of Dexmedetomidine.

Dextroamphetamine: The MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of the amphetamine, Dextroamphetamine. Concomitant therapy should be avoided.

Dextromethorphan: Increased risk of serotonin syndrome. Concomitant use should be avoided.

Diethylpropion: Possible hypertensive crisis

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

Donepezil: Possible antagonism of action

Doxepin: Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.

Duloxetine: Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.

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

Entacapone: Additive inhibition of endogenous catecholamine metabolism may increase the therapeutic/adverse effects of both agents. Concomitant therapy should be avoided.

Ephedrine: The MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of Ephedrine. Concomitant therapy should be avoided.

Epinephrine: Increased arterial pressure

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

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

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

Escitalopram: Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.

Fenfluramine: Possible hypertensive crisis

Fenoterol: Increased arterial pressure

Fentanyl: Possible increased risk of serotonin syndrome.

Fluoxetine: Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.

Fluvoxamine: Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.

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

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

Galantamine: Possible antagonism of action

Guanethidine: Tranylcypromine may decrease the effect of guanethidine.

Ifosfamide: Tranylcypromine, a strong CYP2A6 inhibitor, may decrease the metabolism and clearance of Ifosmadine.

Imipramine: Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.

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

Levodopa: Levodopa may increase the adverse effects of Tranylcypromine. Risk of severe hypertension. Concomitant therapy should be avoided or monitored closely for adverse effects of Tranylcypromine.

Linezolid: The MAO inhibitor, Tranylcypromine, may increase the adverse effects of Linezolid. These agents should not be administered within 14 days of each other.

Lisdexamfetamine: The MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of the amphetamine, Lisdexamfetamine. Concomitant therapy should be avoided.

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

Maprotiline: Maprotiline may increase the adverse effects of the MAO inhibitor, Tranylcypromine. These agents should not be administered within 14 days of each other.

Mazindol: Possible hypertensive crisis

Meperidine: Increased risk of serotonin syndrome. Concomitant use should be avoided.

Mephentermine: The MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of the alpha1-agonist, Mephentermine. Concomitant therapy should be avoided.

Methamphetamine: The MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of the amphetamine, Methamphetamine. Concomitant therapy should be avoided.

Methotrimeprazine: Possible severe adverse reaction with this combination

Methoxamine: The MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of the alpha1-agonist, Methoxamine. Concomitant therapy should be avoided.

Methyldopa: The MAO inhibitor, Tranylcypromine, may increase the adverse effects of Methyldopa. Concomitant therapy is contraindicated.

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

Methylphenidate: The MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of Methylphenidate. Concomitant therapy is contraindicated.

Midodrine: The MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of the alpha1-agonist, Midodrine. Concomitant therapy should be avoided.

Milnacipran: Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.

Mirtazapine: The MAO inhibitor, Tranylcypromine, may increase the central neurotoxic effects of the Mirtazapine. These agents should not be administered within 14 days of each other.

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

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

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

Nortriptyline: Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.

Orciprenaline: Increased arterial pressure

Oxymetazoline: The MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of the alpha1-agonist, Oxymetazoline. Concomitant therapy should be avoided.

Paroxetine: Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.

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

Phendimetrazine: The MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of the amphetamine, Phendimetrazine. Concomitant therapy should be avoided.

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

Phentermine: The MAO inhibitor, tranylcypromine, may increase the vasopressor effect of the amphetamine, phentermine. Concomitant therapy should be avoided.

Phenylephrine: The MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of the alpha1-agonist, Phenylephrine. Concomitant therapy should be avoided.

Phenylpropanolamine: Increased arterial pressure

Pramlintide: The anticholinergic effects of Tranylcypromine may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.

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

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

Propoxyphene: Increased risk of serotonin syndrome. Concomitant use should be avoided.

Protriptyline: Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.

Pseudoephedrine: The MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of Pseudoephedrine. Concomitant therapy should be avoided.

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

Remifentanil: Possible increased risk of serotonin syndrome.

Reserpine: Addition of Reserpine to Tranylcypromine therapy may induce paradoxical Reserpine effects, including peripheral hypertension and central exciation. Close monitoring for adverse effects is required. Addition of Tranylcypromine to Reserpine therapy may be less of a concern.

Rizatriptan: The MAO inhibitor, Tranylcypromine, may reduce the metabolism and clearance of the serotonin 5-HT1D receptor agonist, Rizatriptan. Risk of serotonin syndrome and Rizatriptan toxicity. Concomitant therapy should be avoided.

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

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

Sertraline: Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.

Sibutramine: Increased risk of serotonin syndrome. Avoid concomitant therapy.

St. John's Wort: Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.

Sufentanil: Possible increased risk of serotonin syndrome.

Sumatriptan: The MAO inhibitor, Tranylcypromine, may reduce the metabolism and clearance of the serotonin 5-HT1D receptor agonist, Sumatriptan. Risk of serotonin syndrome and Sumatriptan toxicity. Concomitant therapy should be avoided.

Tacrine: The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Tranylcypromine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by Tranylcypromine, a CYP1A2 inhibitor. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or if doses are changed.

Tamoxifen: The CYP2D6 inhibitor, Tranylcypromine, may decrease the efficacy of Tamoxifen by reducing active metabolite production. Consider alternate therapy.

Tamsulosin: Tranylcypromine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Tranylcypromine is initiated, discontinued, or dose changed.

Terbutaline: Increased arterial pressure

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

Thioridazine: Tranylcypromine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Thioridazine. Concomitant therapy is contraindicated.

Tizanidine: Tranylcypromine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.

Tolcapone: Tolcapone and Tranylcypromine 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, tranylcypromine. Tranylcypromine may decrease the effect of tramadol by decreasing active metabolite production.

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

Trimethobenzamide: Trimethobenzamide and Tranylcypromine, 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: Concomitant therapy with triprolidine and tranylcypromine, two anticholinergics and CNS depressants, may result in additive adverse/toxic effects. Monitor for enhanced anticholinergic and CNS depressant effects during concomitant therapy.

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

Venlafaxine: Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.

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

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