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Major depression: Treatment of major depressive episode without melancholia
Cerebrovascular defect (suspected or confirmed); cardiovascular disease (including hypertension); pheochromocytoma; liver disease or abnormal liver function tests; history of headache.
Concurrent use of antihistamines, antihypertensives, antiparkinson drugs, bupropion, buspirone, caffeine (excessive use), CNS depressants (eg, alcohol, opioids), dextromethorphan, diuretics, elective surgery requiring general anesthesia (discontinue tranylcypromine ≥10 days prior to elective surgery), cocaine or local anesthesia containing sympathomimetic vasoconstrictors, meperidine, MAO inhibitors or dibenzazepine derivatives (eg, amitriptyline, clomipramine, desipramine, imipramine, nortriptyline, protriptyline, doxepin, carbamazepine, cyclobenzaprine, amoxapine, maprotiline, perphenazine, trimipramine), SSRIs or SNRIs, spinal anesthesia (hypotension may be exaggerated), sympathomimetics (including amphetamines, over the counter cold medications, weight reducing agents) or related compounds (dopamine, guanethidine, methyldopa, reserpine, levodopa, tryptophan), or foods high in tyramine content (or within 2 weeks of stopping treatment)
Bupropion: At least 14 days should elapse between MAO inhibitor discontinuation and bupropion initiation.
Buspirone: At least 10 days should elapse between tranylcypromine discontinuation and buspirone initiation.
MAO inhibitors or dibenzazepine derivatives: At least 1 week should elapse between the use of another MAO inhibitor or dibenzazepine derivative and tranylcypromine use.
Meperidine: At least 2 to 3 weeks should elapse between MAO inhibitor discontinuation and meperidine use.
SSRIs or SNRIs: At least 2 weeks should elapse between the discontinuation of sertraline or paroxetine and the initiation of tranylcypromine. At least 5 weeks should elapse between the discontinuation of fluoxetine and the initiation of tranylcypromine. At least 1 week should elapse between discontinuation of a SNRI (eg, venlafaxine) and the initiation of tranylcypromine. At least 2 weeks should elapse between the discontinuation of tranylcypromine and the initiation of SNRIs and SSRIs.
Canadian labeling: Additional contraindications (not in US labeling): Previous hypersensitivity to tranylcypromine or any component of the formulation; blood dyscrasias.
Documentation of allergenic cross-reactivity for monoamine oxidase inhibitors is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Antidepressants increased the risk compared with placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of tranylcypromine or any other antidepressant in a child, adolescent, or young adult must balance the risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared with placebo in adults older than 24 years; there was a reduction in risk with antidepressants compared with placebo in adults 65 years and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Closely observe and appropriately monitor patients of all ages who are started on antidepressant therapy for clinical worsening, suicidality, or unusual changes in behavior. Advise families and caregivers of the need for close observation and communication with the health care provider. Tranylcypromine is not approved for use in pediatric patients.
Major depression: Oral: Initial: 10 mg/day; if symptoms do not improve after 2 weeks, increase dose by 10 mg/day increments at 1- to 3-week intervals; usual dosage range 30 to 60 mg/day in divided doses (APA 2010).
Discontinuation of therapy: Upon discontinuation of antidepressant therapy, gradually taper the dose to minimize the incidence of withdrawal symptoms and allow for the detection of re-emerging symptoms. Evidence supporting ideal taper rates is limited. APA and NICE guidelines suggest tapering therapy over at least several weeks with consideration to the half-life of the antidepressant; antidepressants with a shorter half-life and MAO inhibitors may need to be tapered more conservatively. In addition for long-term treated patients, WFSBP guidelines recommend tapering over 4 to 6 months. If intolerable withdrawal symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate (APA 2010; Bauer 2002; Haddad 2001; NCCMH 2010; Schatzberg 2006; Shelton 2001; Warner 2006).
MAO inhibitor recommendations:
Switching to or from an MAO inhibitor intended to treat psychiatric disorders:
Allow 14 days to elapse between discontinuing an alternative antidepressant without long half-life metabolites (eg, TCAs, paroxetine, fluvoxamine, venlafaxine) or MAO inhibitor intended to treat psychiatric disorders and initiation of tranylcypromine.
Allow at least 5 weeks to elapse between discontinuing fluoxetine (with long half-life metabolites) intended to treat psychiatric disorders and initiation of tranylcypromine.
Allow at least 14 days to elapse between discontinuing tranylcypromine and initiation of an alternative antidepressant or MAO inhibitor intended to treat psychiatric disorders.
Use with other MAO inhibitors (such as linezolid or IV methylene blue):
Do not initiate tranylcypromine in patients receiving linezolid or IV methylene blue; consider other interventions for psychiatric condition.
If urgent treatment with linezolid or IV methylene blue is required in a patient already receiving tranylcypromine and potential benefits outweigh potential risks, discontinue tranylcypromine promptly and administer linezolid or IV methylene blue. Monitor for serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or IV methylene blue, whichever comes first. May resume tranylcypromine 24 hours after the last dose of linezolid or IV methylene blue.
Select dose with caution; refer to adult dosing.
There are no dosage adjustments provided in the manufacturers labeling; use with caution, possible cumulative effects may occur.
There are no dosage adjustments provided in the manufacturers labeling; use is contraindicated in patients with a history of liver disease or abnormal liver function tests.
Avoid tyramine-containing foods/beverages in conjunction with tranylcypromine (or within 2 weeks of stopping therapy). Some examples include aged or matured cheese, air-dried or cured meats (including sausages and salamis), fava or broad bean pods, tap/draft beers, Marmite concentrate, sauerkraut, soy sauce and other soybean condiments. Foods freshness is also an important concern; improperly stored or spoiled food can create an environment where tyramine concentrations may increase.
Store at 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Parnate: 10 mg [contains fd&c blue #2 (indigotine), fd&c red #40, fd&c yellow #6 (sunset yellow)]
Generic: 10 mg
AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Agomelatine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Agomelatine. Monitor therapy
Alcohol (Ethyl): May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Alpha-/Beta-Agonists (Indirect-Acting): MAO Inhibitors may enhance the hypertensive effect of Alpha-/Beta-Agonists (Indirect-Acting). While linezolid is expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to linezolid specific monographs for details. Avoid combination
Alpha1-Agonists: MAO Inhibitors may enhance the hypertensive effect of Alpha1-Agonists. While linezolid is expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to linezolid specific monographs for details. Avoid combination
Altretamine: May enhance the orthostatic hypotensive effect of MAO Inhibitors. Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification
Amodiaquine: CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine. Avoid combination
Amphetamines: MAO Inhibitors may enhance the hypertensive effect of Amphetamines. While linezolid and tedizolid may interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Avoid combination
Analgesics (Opioid): Anticholinergic Agents may enhance the adverse/toxic effect of Analgesics (Opioid). Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy
Analgesics (Opioid): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Monitor therapy
Antidepressants (Serotonin Reuptake Inhibitor/Antagonist): MAO Inhibitors may enhance the adverse/toxic effect of Antidepressants (Serotonin Reuptake Inhibitor/Antagonist). While methylene blue and linezolid are expected to interact, specific recommendations for their use differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Avoid combination
Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy
Apraclonidine: MAO Inhibitors may enhance the adverse/toxic effect of Apraclonidine. MAO Inhibitors may increase the serum concentration of Apraclonidine. Avoid combination
Artesunate: CYP2A6 Inhibitors may decrease serum concentrations of the active metabolite(s) of Artesunate. CYP2A6 Inhibitors may increase the serum concentration of Artesunate. Avoid combination
AtoMOXetine: MAO Inhibitors may enhance the neurotoxic (central) effect of AtoMOXetine. Avoid combination
Atropine (Ophthalmic): MAO Inhibitors may enhance the hypertensive effect of Atropine (Ophthalmic). Avoid combination
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Beta2-Agonists: MAO Inhibitors may enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy
Betahistine: MAO Inhibitors may increase the serum concentration of Betahistine. Monitor therapy
Bezafibrate: MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid combination
Blood Glucose Lowering Agents: MAO Inhibitors may enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Brimonidine (Ophthalmic): MAO Inhibitors may enhance the adverse/toxic effect of Brimonidine (Ophthalmic). MAO Inhibitors may increase the serum concentration of Brimonidine (Ophthalmic). Monitor therapy
Brimonidine (Topical): MAO Inhibitors may enhance the adverse/toxic effect of Brimonidine (Topical). MAO Inhibitors may increase the serum concentration of Brimonidine (Topical). Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Buprenorphine: May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
BuPROPion: MAO Inhibitors may enhance the hypertensive effect of BuPROPion. Avoid combination
BusPIRone: May enhance the adverse/toxic effect of MAO Inhibitors. Specifically, blood pressure elevations been reported. Avoid combination
Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Exceptions: Cannabidiol. Monitor therapy
CarBAMazepine: May enhance the adverse/toxic effect of MAO Inhibitors. Management: Avoid concurrent use of carbamazepine during, or within 14 days of discontinuing, treatment with a monoamine oxidase inhibitor. Avoid combination
Cilostazol: CYP2C19 Inhibitors may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in patients who are also receiving inhibitors of CYP2C19. Consider therapy modification
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination
Clemastine: MAO Inhibitors may enhance the anticholinergic effect of Clemastine. Monitor therapy
Clopidogrel: CYP2C19 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Due to a risk for impaired clopidogrel effectiveness with such a combination, carefully consider the need for a moderate CYP2C19 inhibitor in patients receiving clopidogrel. Monitor patients closely for evidence of a diminished response to clopidogrel. Consider therapy modification
Codeine: MAO Inhibitors may enhance the adverse/toxic effect of Codeine. Monitor therapy
COMT Inhibitors: May enhance the adverse/toxic effect of MAO Inhibitors. Consider therapy modification
Cyclobenzaprine: May enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Avoid combination
CYP1A2 Substrates: CYP1A2 Inhibitors (Moderate) may decrease the metabolism of CYP1A2 Substrates. Monitor therapy
CYP2A6 Substrates: CYP2A6 Inhibitors (Strong) may decrease the metabolism of CYP2A6 Substrates. Consider therapy modification
CYP2C19 Substrates: CYP2C19 Inhibitors (Moderate) may decrease the metabolism of CYP2C19 Substrates. Monitor therapy
Cyproheptadine: MAO Inhibitors may enhance the anticholinergic effect of Cyproheptadine. Cyproheptadine may diminish the serotonergic effect of MAO Inhibitors. Avoid combination
Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Avoid combination
Dexmethylphenidate: MAO Inhibitors may enhance the hypertensive effect of Dexmethylphenidate. Avoid combination
Dextromethorphan: MAO Inhibitors may enhance the serotonergic effect of Dextromethorphan. This may cause serotonin syndrome. Avoid combination
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Diethylpropion: MAO Inhibitors may enhance the hypertensive effect of Diethylpropion. Avoid combination
Domperidone: MAO Inhibitors may enhance the adverse/toxic effect of Domperidone. MAO Inhibitors may diminish the therapeutic effect of Domperidone. Domperidone may diminish the therapeutic effect of MAO Inhibitors. Monitor therapy
Doxapram: MAO Inhibitors may enhance the hypertensive effect of Doxapram. Monitor therapy
Doxylamine: MAO Inhibitors may enhance the anticholinergic effect of Doxylamine. Management: The US manufacturer of Diclegis (doxylamine/pyridoxine) and the manufacturers of Canadian doxylamine products specifically lists use with monoamine oxidase inhibitors as contraindicated. Monitor therapy
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination
EPINEPHrine (Nasal): MAO Inhibitors may enhance the hypertensive effect of EPINEPHrine (Nasal). Monitor therapy
EPINEPHrine (Oral Inhalation): MAO Inhibitors may enhance the hypertensive effect of EPINEPHrine (Oral Inhalation). Avoid combination
Epinephrine (Racemic): MAO Inhibitors may enhance the hypertensive effect of Epinephrine (Racemic). Monitor therapy
EPINEPHrine (Systemic): MAO Inhibitors may enhance the hypertensive effect of EPINEPHrine (Systemic). Monitor therapy
FentaNYL: May enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Avoid combination
Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Avoid combination
Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
HYDROcodone: MAO Inhibitors may enhance the adverse/toxic effect of HYDROcodone. Management: Consider alternatives to this combination when possible. Consider therapy modification
HYDROmorphone: MAO Inhibitors may enhance the adverse/toxic effect of HYDROmorphone. Avoid combination
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Isometheptene: MAO Inhibitors may enhance the adverse/toxic effect of Isometheptene. Avoid combination
Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy
Levodopa: May enhance the adverse/toxic effect of MAO Inhibitors. Of particular concern is the development of hypertensive reactions when levodopa is used with nonselective MAOI. Management: The concomitant use of nonselective monoamine oxidase inhibitors (MAOIs) and levodopa is contraindicated. Discontinue the nonselective MAOI at least two weeks prior to initiating levodopa. Monitor patients taking a selective MAOIs and levodopa. Consider therapy modification
Levonordefrin: MAO Inhibitors may enhance the hypertensive effect of Levonordefrin. Avoid combination
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination
Linezolid: MAO Inhibitors may enhance the adverse/toxic effect of Linezolid. Avoid combination
Lithium: MAO Inhibitors may enhance the adverse/toxic effect of Lithium. Management: This combination should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome. Consider therapy modification
MAO Inhibitors: May enhance the hypertensive effect of other MAO Inhibitors. MAO Inhibitors may enhance the serotonergic effect of other MAO Inhibitors. This could result in serotonin syndrome. Avoid combination
Maprotiline: May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
Meperidine: MAO Inhibitors may enhance the serotonergic effect of Meperidine. This may cause serotonin syndrome. Avoid combination
Mequitazine: MAO Inhibitors may enhance the anticholinergic effect of Mequitazine. Avoid combination
Metaraminol: MAO Inhibitors may enhance the hypertensive effect of Metaraminol. Monitor therapy
Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Methadone: May enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Monitor therapy
Methyldopa: MAO Inhibitors may enhance the adverse/toxic effect of Methyldopa. Avoid combination
Methylene Blue: MAO Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Avoid combination
Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Avoid combination
Methylphenidate: MAO Inhibitors may enhance the hypertensive effect of Methylphenidate. Avoid combination
Metoclopramide: Serotonin Modulators may enhance the adverse/toxic effect of Metoclopramide. This may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Monitor therapy
Mianserin: MAO Inhibitors may enhance the neurotoxic effect of Mianserin. Avoid combination
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy
Mirtazapine: MAO Inhibitors may enhance the neurotoxic (central) effect of Mirtazapine. While methylene blue and linezolid are expected to interact, specific recommendations for their use differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Avoid combination
Moclobemide: MAO Inhibitors may enhance the adverse/toxic effect of Moclobemide. Avoid combination
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Morphine (Liposomal): MAO Inhibitors may enhance the adverse/toxic effect of Morphine (Liposomal). Avoid combination
Morphine (Systemic): MAO Inhibitors may enhance the adverse/toxic effect of Morphine (Systemic). Avoid combination
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nefopam: MAO Inhibitors may enhance the adverse/toxic effect of Nefopam. Avoid combination
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy
Norepinephrine: MAO Inhibitors may enhance the hypertensive effect of Norepinephrine. Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification
OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Monitor therapy
Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
OxyCODONE: MAO Inhibitors may enhance the adverse/toxic effect of OxyCODONE. Management: Per Canadian labeling, use of oxycodone is contraindicated in patients who either are receiving MAO inhibitors or have used them within 14 days. Though not contraindicated in U.S. prescribing information, consider alternatives when possible. Consider therapy modification
OxyMORphone: May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Pheniramine: May enhance the anticholinergic effect of MAO Inhibitors. Avoid combination
Pholcodine: May enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Avoid combination
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Pindolol: MAO Inhibitors may enhance the hypotensive effect of Pindolol. Management: Canadian labeling for pindolol states that concurrent use with a monoamine oxidase inhibitor is not recommended. Consider therapy modification
Pirfenidone: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pirfenidone. Management: Use any such combination with caution and close monitoring for pirfenidone toxicity. Avoid the use of pirfenidone with moderate CYP1A2 inhibitors whenever CYP2C9, 2C19, 2C6, or 2E1 is also inhibited (either by the CYP1A2 inhibitor or by a third drug). Consider therapy modification
Pizotifen: MAO Inhibitors may enhance the anticholinergic effect of Pizotifen. Avoid combination
Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Avoid combination
Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy
Reboxetine: MAO Inhibitors may enhance the adverse/toxic effect of Reboxetine. Avoid combination
Reserpine: MAO Inhibitors may enhance the adverse/toxic effect of Reserpine. Existing MAOI therapy can result in paradoxical effects of added reserpine (e.g., excitation, hypertension). Management: Monoamine oxidase inhibitors (MAOIs) should be avoided or used with great caution in patients who are also receiving reserpine. Consider therapy modification
RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy
Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid using drugs with substantial anticholinergic effects in patients receiving secretin whenever possible. If such agents must be used in combination, monitor closely for a diminished response to secretin. Consider therapy modification
Selective Serotonin Reuptake Inhibitors: MAO Inhibitors may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Avoid combination
Serotonin 5-HT1D Receptor Agonists: MAO Inhibitors may decrease the metabolism of Serotonin 5-HT1D Receptor Agonists. Management: If MAO inhibitor therapy is required, naratriptan, eletriptan or frovatriptan may be a suitable 5-HT1D agonist to employ. Exceptions: Eletriptan; Frovatriptan; Naratriptan. Avoid combination
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid. Monitor therapy
Serotonin/Norepinephrine Reuptake Inhibitors: MAO Inhibitors may enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Avoid combination
Tapentadol: May enhance the adverse/toxic effect of MAO Inhibitors. Specifically, the additive effects of norepinephrine may lead to adverse cardiovascular effects. Tapentadol may enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Avoid combination
Tegafur: CYP2A6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Tegafur. Specifically, CYP2A6 inhibitors may inhibit the conversion of tegafur into its active metabolite, 5-fluorouracil. Avoid combination
Tetrabenazine: May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
Tetrahydrozoline (Nasal): MAO Inhibitors may enhance the hypertensive effect of Tetrahydrozoline (Nasal). Avoid combination
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy
Tianeptine: May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination
TiZANidine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of TiZANidine. Management: If combined use cannot be avoided, initiate tizanidine in adults at 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Avoid combination
Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Monitor therapy
TraMADol: Serotonin Modulators may enhance the adverse/toxic effect of TraMADol. The risk of seizures may be increased. TraMADol may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Tricyclic Antidepressants: MAO Inhibitors may enhance the serotonergic effect of Tricyclic Antidepressants. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Avoid combination
Tryptophan: May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Blood glucose, renal and hepatic function; blood pressure, heart rate, mental status, worsening of depression, suicidality, or unusual changes in behavior (especially at the beginning of therapy or when doses are increased or decreased)
Frequency not defined:
Cardiovascular: Edema, orthostatic hypotension, palpitation, tachycardia
Central nervous system: Agitation, anxiety, chills, dizziness, drowsiness, headache, insomnia, mania, restlessness
Dermatologic: Alopecia (rare), rash (rare), urticaria
Endocrine & metabolic: Sexual dysfunction (anorgasmia, ejaculatory disturbances, impotence); SIADH
Gastrointestinal: Abdominal pain, anorexia, constipation, diarrhea, nausea, xerostomia
Genitourinary: Urinary retention
Hematologic: Agranulocytosis, anemia, leukopenia, thrombocytopenia
Hepatic: Hepatitis (rare)
Neuromuscular & skeletal: Muscle spasm, myoclonus, numbness, paresthesia, tremor, weakness
Ocular: Blurred vision
Otic: Tinnitus
Miscellaneous: Diaphoresis
Postmarketing and/or case reports: Akinesia, ataxia, confusion, cystic acne, disorientation, memory loss, mouth fissures, polyuria, scleroderma (localized), urinary incontinence, urticaria, withdrawal symptoms
Major psychiatric warnings:
- Suicidal thinking/behavior: [US Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient 's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Tranylcypromine is not approved for use in pediatric patients.
- The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.
- Prescriptions should be written for the smallest quantity consistent with good patient care. The patients family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression occur.
Concerns related to adverse effects:
- CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).
- Hypertensive crisis: Cases of hypertensive crisis (sometimes fatal) have occurred; symptoms include: occipital headache which may radiate frontally, nausea/vomiting, neck stiffness/soreness, palpitation, photophobia, and sweating. Tachycardia and bradycardia may be present, and associated constricting chest pain and dilated pupils may occur. Monitor blood pressure closely in all patients; discontinue immediately if palpitation or frequent headaches occur. May occur with foods/supplements high in tyramine, tryptophan, phenylalanine, or tyrosine content; treatment with phentolamine is recommended for hypertensive crisis.
- Hypotension: May cause postural hypotension (especially at dosages >30 mg/day) and may result in syncope; use with caution in patients at risk of this effect, patents with preexisting hypertension, or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia). Increase dosage more gradually in patients showing a tendency toward hypotension.
- Intracranial bleeding: Intracranial bleeding (some fatal) have been reported in association with the paradoxical increase in blood pressure.
Disease-related concerns:
- Angina: May mask anginal pain.
- Diabetes: Use with caution in patients with diabetes mellitus; may increase the risk of hypoglycemic episodes, monitor blood glucose closely in diabetic patients receiving insulin or oral hypoglycemic agents.
- Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency may exist, especially in patients using doses exceeding the therapeutic range.
- Mania/hypomania: May precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder. Tranylcypromine is not approved for the treatment of bipolar depression.
- Renal impairment: Use with caution in patients with renal impairment; possible cumulative effects may occur.
- Seizure disorder: Use with caution in patients at risk for seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold.
- Thyroid dysfunction: Use with caution in patients with hyperthyroidism.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Surgical patients: Tranylcypromine use within 10 days prior to elective surgery is contraindicated. The decision to continue or withhold MAO inhibitors must be done in collaboration with the patient's psychiatrist. Currently, an MAO-safe anesthetic technique which excludes the use of meperidine and indirect-acting adrenergic agonists is recommended for patients requiring continued MAO inhibitor therapy (Huyse 2006).
Other warnings/precautions:
- Appropriate use: Tranylcypromine is not generally considered a first-line agent for the treatment of depression; tranylcypromine is typically used in patients who have failed to respond to other treatments.
- Discontinuation syndrome: Abrupt discontinuation or interruption of antidepressant therapy has been associated with a discontinuation syndrome. Symptoms arising may vary with antidepressant however commonly include nausea, vomiting, diarrhea, headaches, lightheadedness, dizziness, diminished appetite, sweating, chills, tremors, paresthesias, fatigue, somnolence, and sleep disturbances (eg, vivid dreams, insomnia). Less common symptoms include electric shock-like sensations, cardiac arrhythmias (more common with tricyclic antidepressants), myalgias, parkinsonism, arthralgias, and balance difficulties. Psychological symptoms may also emerge such as agitation, anxiety, akathisia, panic attacks, irritability, aggressiveness, worsening of mood, dysphoria, mood lability, hyperactivity, mania/hypomania, depersonalization, decreased concentration, slowed thinking, confusion, and memory or concentration difficulties. Greater risks for developing a discontinuation syndrome have been associated with antidepressants with shorter half-lives, longer durations of treatment, and abrupt discontinuation. More severe symptoms have also been associated with MAO inhibitors. For antidepressants of short or intermediate half-lives, symptoms may emerge within 2 to 5 days after treatment discontinuation and last 7 to 14 days (APA 2010; Fava 2006; Haddad 2001; Shelton 2001; Warner 2006).
- Myelography: Discontinue at least 48 hours prior to myelography; do not resume therapy until at least 24 hours after procedure.
Information related to the use of tranylcypromine in pregnancy is limited (Kennedy 2000).
Pregnant women exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants (NPRAD). Women 18 to 45 years of age or their health care providers may contact the registry by calling 844-405-6185. Enrollment should be done as early in pregnancy as possible.
Tranylcypromine is a nonhydrazine monoamine oxidase inhibitor. It increases endogenous concentrations of epinephrine, norepinephrine, and serotonin through inhibition of the enzyme (monoamine oxidase) responsible for the breakdown of these neurotransmitters.
Rapid (Mallinger 1990)
Therapeutic: 2 days to 3 weeks continued dosing
Serum: 1.5 hours (Mallinger 1990)
MAO inhibition may persist for up to 10 days following discontinuation.
2.5 hours (Mallinger 1990)
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience fatigue, constipation, insomnia, dry mouth, abdominal pain, diarrhea, or loss of strength and energy. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, illogical thinking), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), chills, angina, shortness of breath, severe behavioral changes, severe headache, severe nausea, vomiting, severe dizziness, passing out, arrhythmia, sweating a lot, neck rigidity, sensitivity to light, severe anxiety, irritability, mood changes, agitation, blurred vision, sexual dysfunction, bradycardia, tachycardia, or larger pupils (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.