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Tranylcypromine

Pronunciation

(tran il SIP roe meen)

Index Terms

  • Transamine Sulphate
  • Tranylcypromine Sulfate

Dosage Forms

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

Brand Names: U.S.

  • Parnate

Pharmacologic Category

  • Antidepressant, Monoamine Oxidase Inhibitor

Pharmacology

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.

Absorption

Rapid (Mallinger 1990)

Onset of Action

Therapeutic: 2 days to 3 weeks continued dosing

Time to Peak

Serum: 1.5 hours (Mallinger 1990)

Duration of Action

MAO inhibition may persist for up to 10 days following discontinuation.

Half-Life Elimination

2.5 hours (Mallinger 1990)

Use: Labeled Indications

Major depression: Treatment of major depressive episode without melancholia

Contraindications

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.

Dosing: Adult

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.

Dosing: Geriatric

Select dose with caution; refer to adult dosing.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer's labeling; use with caution, possible cumulative effects may occur.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer's labeling; use is contraindicated in patients with a history of liver disease or abnormal liver function tests.

Dietary Considerations

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. Food's freshness is also an important concern; improperly stored or spoiled food can create an environment where tyramine concentrations may increase.

Storage

Store at 15°C to 30°C (59°F to 86°F).

Drug Interactions

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: May enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Management: Seek alternatives when possible. Avoid use of oxycodone/naltrexone during and within 14 days of stopping monoamine oxidase inhibitor treatment. Non-US labeling for some oxycodone products states that such use is contraindicated. 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

Adverse Reactions

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

ALERT: U.S. Boxed Warning

Suicidality and antidepressant drugs:

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.

Warnings/Precautions

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 patient's 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.

Monitoring Parameters

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)

Pregnancy Considerations

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.

Patient Education

• 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.

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