increase serotonin levels. Avoid or Use Alternate Drug. tranylcypromine increases levels of zolmitriptan by decreasing metabolism. Contraindicated. Frequency Not Defined Orthostatic hypotension Dizziness Headache Drowsiness Sleep disturbance Fatigue Weakness Tremor Hyperreflexia Constipation Dry mouth Confusion Decr memory Nystagmus Paresthesia Anorexia N/V Impotence Urinary frequency or retention Anxiety Irritation Hypomania "Hypermetabolic syndrome" (hyperpyrexia, tachycardia, tachypnea, incr CPK, acidosis) Arthralgia Edema SIADH (rare) Risk of hypertensive crisis (rare,usu d/t drug interaction) Ataxia (rare) Seizure (rare) Jaundice (rare) Visual disturbance (rare) Postmarketing Reports Myasthenia gravis Lambert-Eaton myasthenic syndrome Black Box Warnings In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 yr of age) taking antidepressants for major depressive disorders and other psychiatric illnesses This increase was not seen in patients aged >24 years; a slight decrease in suicidal thinking was seen in adults >65 years In children and young adults, risks must be weighed against the benefits of taking antidepressants Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; this should be done during initial 1-2 months of therapy and dosage adjustments The patient’s family should communicate any abrupt changes in behavior to the healthcare provider Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy This drug is not approved for use in pediatric patients Hypertensive Crisis with Significant Tyramine Use Excessive consumption of foods or beverages with significant tyramine content or use of certain drugs during or after therapy discontinuation can precipitate hypertensive crisis; monitor blood pressure and allow for medication-free intervals between administration of therapy and interacting drugs; instruct patients to avoid ingestion of foods and beverages with high tyramine content Contraindications Hypersensitivity Pheochromocytoma, CHF, cerebrovascular defect, CVD, HTN Schizophrenia History of severe or frequent headaches, liver disease Contraindicated with MAOIs or dibenzazepine-related drugs, sympathomimetics (including amphetamines, which may be found in many herbal preparations), methylphenidates and derivatives, some CNS depressants (eg, narcotics, alcohol), antihypertensives, diuretics, antihistamines, sedatives, anesthetics, bupropion, buspirone, dextromethorphan, meperidine, SSRIs (eg, fluoxetine, paroxetine, sertraline), SNRIs (eg, venlafaxine), levodopa, s-adenosyl-L-methionine (SAM-e), tricyclic antidepressants, other antidepressants (eg, amoxapine, bupropion, maprotiline, nefazodone, trazodone, vilazodone, vortioxetine), carbamazepine, tapentadol, cyclobenzaprine, methyldopa, tetrabenazine, milnacipran, tryptophan, dopamine, rasagiline, hydroxytryptophan, reserpine, triptans Sympathomimetic products (e.g., cold, hay fever or weight-reducing products that contain vasoconstrictors such as pseudoephedrine, phenylephrine, and ephedrine; or dietary supplements that contain sympathomimetics); may cause cerebral hemorrhage Discontinue 10 days before surgery High tyramine content food (eg, cheese, beer, Chianti wine, avocados, anchovies, herring, overripe fruit, chocolate, soy sauce, yeasts, yogurt, meat tenderizers, sauerkraut, broad beans) Pheochromocytoma and catecholamine-releasing paragangliomas Cautions Clinical worsening & suicide ideation may occur despite medication in adolescents & young adults (18-24 years) Caution in patients with diabetes mellitus (monitor glucose closely), glaucoma, hepatic/renal impairment, thyroid dysfunction Some MAOIs have contributed to hypoglycemic episodes in diabetic patients receiving insulin or other blood-glucose-lowering agents; monitor blood glucose in patients receiving both this drug and blood-glucose-lowering agents; a reduction of the dosage of such agents may be necessary Seizures reported with therapy withdrawal after abuse, and with overdose; patients with history or at risk for seizures should be monitored accordingly Drug may worsen psychosis in patients with bipolar disorder Therapy may aggravate coexisting symptoms in depression, such as anxiety and agitation Although excretion of this drug is rapid, inhibition of MAO may persist up to 10 days following discontinuation; this should be taken into account when considering use of potential interacting substances or consumption of tyramine-rich food or beverages or when interpreting adverse reactions observed after discontinuation; care should be taken to differentiate symptoms of persistent MAO inhibition from withdrawal symptoms Activation of mania/hypomania may be precipitated by antidepressant treatment in patients with bipolar disorder; screen patients prior to treatment, prior to initiating treatment, screen patients for any personal or family history of bipolar disorder, mania, or hypomania Hypotension and hypertension during anesthesia and perioperative care may occur; it is recommended that therapy be discontinued at least 10 days prior to elective surgery; if this is not possible, for general anesthesia, regional and local anesthesia, and perioperative care, avoid use of agents that are contraindicated for concomitant use with this drug; carefully consider risk of agents and techniques that increase risk for hypotension (eg, epidural or spinal anesthesia) or other adverse reactions to this drug (eg, hypertension associated with use of vasoconstrictors in local anesthetics) If in the absence of therapeutic alternatives emergency treatment with a contraindicated product (eg, linezolid, intravenous methylene blue, direct-acting sympathomimetic drugs such as epinephrine) becomes necessary and cannot be delayed, discontinue therapy as soon as possible before initiating treatment with the other product and monitor closely for adverse reactions Hepatitis and elevated aminotransferases reported in association with administration of therapy; patients should be monitored accordingly; therapy should be discontinued in patients who develop signs and symptoms of hepatotoxicity Sedation has occurred in treated patients with cirrhosis; patients with cirrhosis receiving therapy should be monitored for possible increased risks of central nervous system adverse reactions, such as excessive drowsiness Some adverse reactions (eg, hypotension, faintness, drowsiness, confusion, disorientation) can impair a patient’s ability to operate machinery or use an automobile; patients should be cautioned about operating hazardous machinery, including automobiles until they are reasonably certain that therapy does not impair their ability to engage in such activities Hypotension Hypotension, including postural hypotension, has been observed during therapy; at doses above 30 mg daily, postural hypotension is a major adverse reaction andmay result in syncope; symptoms of postural hypotension are seen most commonly, but not exclusively, in patients with pre-existing hypertension; blood pressure usually returns rapidly to pretreatment levels upon discontinuation of therapy Dosage increases should be made more gradually in patients with a tendency toward hypotension and/or postural hypotension (eg, elderly patients); such patients should be closely observed for postural changesin blood pressure throughout treatment Also, when therapy is used concomitantly with otheragents known to cause hypotension, the possibility of additive hypotensive effects should be considered; postural hypotension may be relieved by having patients lie down until blood pressure returns to normal Hypertensive crisis Associated with hypertensive crises caused by the ingestion of foods or beverages with a high concentration of tyramine; in addition, hypertensive reactions and crises may occur with concomitant use of other drugs; patients with hyperthyroidism may be at greater risk of hypertensive crisis In some patients a hypertensive crisis constitutes a hypertensive emergency, which requires immediate attention to prevent serious complications or fatal outcomes; these emergencies are characterized by severe hypertension (eg, with a blood pressure of more than 180/120 mm Hg) and evidence of organ dysfunction; Symptoms may include occipital headache (which may radiate frontally), palpitations, neck stiffness or soreness, nausea or vomiting, sweating (sometimes with fever or cold, clammy skin), dilated pupils, photophobia, shortness of breath, or confusion Either tachycardia or bradycardia may be present and may be associated with constricting chest pain; seizures may also occur; intracranial bleeding, sometimes fatal, reported in association with increase in blood pressure Strategies to reduce hypertensive crisis Instruct patients to avoid foods and beverages with high tyramine content while receiving therapy and for 2 weeks after stopping therapy Careful evaluation of benefits and risks of therapy is necessary for patients with hypertension or confirmed or suspected cerebrovascular or cardiovascular disorders that constitute an increased risk for complications from severe hypertension, and a history of headaches that can mask the occurrence of headaches as prodromal of a hypertensive crisis Monitor blood pressure closely to detect evidence of increased blood pressure; full reliance should not be placed on blood pressure readings; the patient should also be observed for other signs and symptoms of hypertensive crisis Treatment of hypertensive crisis Therapy should be interrupted with symptoms that may be prodromal or a manifestation of a hypertensive crisis, such as palpitations or headaches, and patients should be evaluated immediately; discontinue therapy, other drugs, foods or beverages suspected to contribute to hypertensive crisis immediately Patients with severe elevations in blood pressure (eg, more than 180/120 mm Hg) with evidence of organ dysfunction require immediate blood pressure reduction Fever should be managed by means of external cooling; additional measures to control causes of hyperthermia(psychomotor agitation, increased neuromuscular activity, persistent seizures) may be required Hypertension Clinically significant increases in blood pressure have been reported after administration of MAOIs, in patients not ingesting tyramine-rich foods or beverages Assess blood pressure before prescribing the drug and closely monitor blood pressure in all patients receiving this therapy Serotonin syndrome Development of potentially life-threatening serotonin syndrome reported with MAOIs when used concomitantly with other serotonergic drugs Such drugs include SSRIs, SNRIs, tricyclic antidepressants, triptans, fentanyl, lithium, tramadol, tryptophan, buspirone,St. John’s wort, S-adenosyl-L-methionine (SAM-e), and other MAOIs used to treat nonpsychiatric disorders (such as linezolid or intravenous methylene blue) Manifestations of serotonin syndrome may include mental status changes (eg, agitation, hallucinations, delirium, coma), autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia; with possible rapid fluctuations of vital signs), neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyper-reflexia, incoordination), seizures, and/or gastrointestinal symptoms (eg, nausea, vomiting, diarrhea) Fatal outcome of serotonin syndrome has been reported, including in patients who had received therapy; in some cases of an interaction between this drug and SSRIs or SNRIs, the features of the syndrome resembled neuroleptic malignant syndrome The concomitant use, or use in rapid succession, of this drug with other serotonergic drugs is contraindicated; however, there may be circumstances when treatment with other serotonergic substances (such as linezolid or intravenous methylene blue) is necessary and cannot be delayed In such cases, discontinue therapy as soon as possible before initiating treatment with other agent; treatment with this drug and any concomitant serotonergic agents should be discontinued immediately if above events occur, and supportive symptomatic treatment should be initiated Discontinuation syndrome Abrupt discontinuation or dosage reduction of this drug has been associated with the appearance of new symptoms that include dizziness, nausea, headache, irritability, insomnia, diarrhea, anxiety, fatigue, abnormal dreams, and hyperhidrosis; in general, discontinuation events occurred more frequently with longer duration of therapy There have been spontaneous reports of adverse reactions occurring upon discontinuation of MAOIs, particularly when abrupt, including dysphoric mood, irritability, agitation, dizziness, sensory disturbances (eg paresthesia, such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures While these reactions are generally self-limiting, there have been reports of prolonged discontinuation symptoms; patients should be monitored for these symptoms when discontinuing treatment with this drug; a gradual reduction in the dose rather than abrupt cessation recommended whenever possible Pregnancy There are limited published reports of placental infarction and congenital anomalies in association with use during pregnancy; however, these reports may not adequately inform presence or absence of drug-associated risk with use of during pregnancy; animal embryo-fetal development studies were not conducted with tranylcypromine; however, published animal reproduction studies report placental transfer of tranylcypromine in rats and a dose-dependent decrease in uterine blood flow in pregnant sheep; advise pregnant women of the potential risk to a fetus Lactation Tranylcypromine is present in human milk; there is no available information on effects of tranylcypromine on milk production; there is no available information on effects of tranylcypromine on a breastfed child; however, because of potential for serious adverse reactions in a breastfed infant, advise nursing women to discontinue breastfeeding during treatmentPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Nonselective monoamine oxidase inhibitor; may inhibit the enzyme monoamine oxidase, which is responsible for the breakdown of dopamine, serotonin, epinephrine, and norepinephrine, in turn causing an increase in endogenous concentrations of these neurotransmitters. Pharmacokinetics Half-life elimination: 1.5-3 hr Onset: 2 days to 3 weeks Duration: Therapeutic effects and interactions may continue for up to 2 weeks after discontinuing therapy Peak plasma time: 1.5-2