ent with an mao inhibitor antidepressant, a time period of at least 1 week or 4 to 5 half-lives of the other mao inhibitor (whichever is longer) should elapse before starting treatment with tranylcypromine tablets because of the risk for clinically significant adverse reactions after discontinuation due to persistent mao inhibition [see dosage and administration (2.2), warnings and precautions (5.9)] . this period can be several weeks long (e.g., a minimum of 5 weeks for fluoxetine given fluoxetine’s long half-life). refer to the prescribing information of the contraindicated product for relevant information. t ime to start contraindicated drug after discontinuation of tranylcypromine tablets the potential for interactions persists after discontinuation of tranylcypromine tablets until mao activity has sufficiently recovered. inhibition of mao may persist up to 10 days following discontinuation [see warnings and precautions (5.9)] . after stopping tranylcypromine tablets, at least 1 week should elapse before starting another maoi (intended to treat mdd) or other contraindicated antidepressants. refer to the prescribing information of any agent considered for subsequent use for recommendations on the duration of a waiting period after discontinuation of a mao inhibitor. if in the absence of therapeutic alternatives and emergency treatment with a contraindicated drug (e.g., linezolid, intravenous methylene blue, direct-acting sympathomimetic drugs such as epinephrine) becomes necessary and cannot be delayed, discontinue tranylcypromine tablets as soon as possible before initiating treatment with the other agent, and monitor closely for adverse reactions. table 3: clinically significant drug interactions with drug classes* p r oduct c linical comment on concomitant usea p r e dominant effect/risk [hypertensive reaction (hr)b or serotonin syndrome (ss)c] agents with blood pressure-reducing effects use with cautiond hypotensione non-selective h1 receptor antagonists contraindicateda increased anticholinergic effects beta-adrenergic blockers (see also agents or procedures with blood pressure-reducing effects) use with cautiond more pronounced bradycardia, postural hypotensione blood glucose-lowering agents dosage reduction of such agents may be necessary. monitor blood glucose. excessive reduction of blood glucose (additive effect)f cns depressant agents (including opioids, alcohol, sedatives, hypnotics) use with cautiond increased cns depression dietary supplements containing sympathomimetics contraindicateda antidepressants including but not limited to: other maois (e.g., linezolid, intravenous methylene blue, selective maois) selective serotonin reuptake inhibitors (ssris) and serotonin and norepinephrine reuptake inhibitors (snris) tricyclic antidepressants amoxapine, bupropion, maprotiline, nefazodone, trazodone, vilazodone, vortioxetine contraindicateda ss for all antidepressants for maois, increased mao inhibition and risk of adverse reactions, ss, and hrg amphetamines and methylphenidates andderivatives contraindicateda hr sympathomimetic drugs** contraindicateda hr; including risk of intracerebral hemorrhage triptans contraindicateda ss * some drugs in these groups may also be listed in table 4 below. ** sympathomimetic drugs include amphetamines as well as cold, hay fever or weight-reducing products that contain vasoconstrictors such as pseudoephedrine, phenylephrine, and ephedrine) a [s ee contraindications (4.1)]; b [s ee warnings and precautions (5.2)]; c [ s ee warnings and precautions (5.3)] d if not otherwise specified in this table, consider avoiding concomitant use (see also information on medication-free intervals, use agent at the lowest appropriate dosage, monitor for effects of the interaction, advise the patient to report potential effects). e [s ee warnings and precautions (5.5)]; f [s ee warnings and precautions (5.14)]; g [s ee overdosage (10.1)] table 4: clinically significant drug interactions with individual products* p r oduct c linical comment on concomitant usea p r e dominant effect/risk [hypertensive reaction (hr)b or serotonin syndrome (ss)c] altretamine use with cautiond orthostatic hypotensione buspirone contraindicateda hr carbamazepine contraindicateda ss chlorpromazine use with cautiond hypotensive effectse cyclobenzaprine contraindicateda ss dextromethorphan contraindicateda ss; psychosis, bizarre behavior dopamine contraindicateda hr droperidol use with cautiond qt interval prolongation entacapone use with cautiond hr fentanyl use with cautiond ss hydroxytryptophan contraindicateda ss levodopa contraindicateda hr lithium use with cautiond ss meperidine contraindicateda ss methadone use with cautiond ss methyldopa contraindicateda hr metoclopramide use with cautiond hr/ss mirtazapine contraindicateda ss oxcarbazepine use with cautiond because of close structural relationship with tricyclic antidepressants ss rasagiline contraindicateda hr reserpine contraindicateda hr s-adenosyl-l-methionine (sam-e) contraindicateda ss tapentadol contraindicateda hr/ss tetrabenazine contraindicateda hr tolcapone use with cautiond hr tramadol use with cautiond ss; increased seizure risk tryptophan contraindicateda ss * some drugs in this table may also belong to groups listed in table 3 above, and may be associated with additional interactions. a [s ee contraindications (4.1)]; b [s ee warnings and precautions (5.3)]; c [ s ee warnings and precautions (5.7)] d if not otherwise specified in this table, consider avoiding concomitant use (see also information on medication-free intervals, use agent at the lowest appropriate dose, monitor for effects of the interaction, advise the patient to report potential effects, and be prepared to discontinue the agent and treat effects of the interaction e [s ee warnings and precautions (5.5) 7.2 tyramine-containing foods and beverages tranylcypromine tablets inhibits intestinal mao, which is responsible for the catabolism of tyramine in food and beverages. as a result of this inhibition, large amounts of tyramine may enter the systemic circulation and precipitate a sudden elevation in blood pressure or hypertensive crisis [see warnings and precautions (5.2)] . instruct tranylcypromine tablet-treated patients to avoid foods and beverages with significant tyramine content during treatment with tranylcypromine tablets or within 2 weeks of stopping treatment (see table 5 for a list of food and beverages containing significant amounts of tyramine). table 5: foods and beverages with and without significant amounts of tyramine c lass of f ood or beverage tyramine-rich foods and beverages to avoid acce ptable foods and dr inks, containing no or little tyramine meat, poultry, and fish air dried, aged and fermented meats, sausages and salamis (including cacciatore, hard salami and mortadella); pickled herring; and any spoiled or improperly stored meat, poultry, and fish (e.g., foods that have undergone changes in coloration, odor, or become moldy); spoiled or improperly stored animal livers fresh meat, poultry, and fish, including fresh processed meats (e.g., lunch meats, hot dogs, breakfast sausage, and cooked sliced ham) vegetables broad bean pods (fava bean pods) all other vegetables dairy aged cheeses processed cheeses, mozzarella, ricotta cheese, cottage cheese, and yogurt beverages all varieties of tap beer and beers that have not been pasteurized so as to allow for ongoing fermentation and excessive amounts of caffeine. concomitant use of alcohol with tranylcypromine tablets is not recommended. (bottled and canned beers and wines contain little or no tyramine.) other concentrated yeast extract (e.g., marmite), sauerkraut, most soybean products (including soy sauce and tofu), otc supplements containing tyramine, and chocolate brewer’s yeast, baker’s yeast, soy milk, commercial chain restaurant pizzas prepared with cheeses low in tyramine

suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied. there were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with mdd. the drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1000 patients treated are provided in table 2. table 2: risk differences of the number of patients of suicidal thoughts and behavior in the pooled placebo-controlled trials of antidepressants in pediatric and adult patients age range drug-placebo difference in number of patients of suicidal thoughts or behaviors per 1000 patients treated increases compared to placebo <18 years old 14 additional patients 18-24 years old 5 additional patients decreases compared to placebo 25-64 years old 1 fewer patient ≥65 years old 6 fewer patients it is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, and young adults extends to longer-term use, i.e., beyond four months. however, there is substantial evidence from placebo-controlled maintenance trials in adults with mdd that antidepressants delay the recurrence of depression and that depression itself is a risk factor for suicidal thoughts and behaviors. monitor all antidepressant-treated patients for any indication for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy, and at times of dosage changes. counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. consider changing the therapeutic regimen, including possibly discontinuing tranylcypromine tablets, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors. 5.2 hypertensive crisis and hypertension h y p er tensive crisis maois, including tranylcypromine tablets, have been 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 [see drug interactions (7.1)] . patients with hyperthyroidism may be at greater risk of hypertensive crisis. signs, symptoms, and complications of hypertensive crisis: in some patients a hypertensive crisis constitutes a hypertensive emergency, which requires immediate attention to prevent serious complications or fatal outcome. these emergencies are characterized by severe hypertension (e.g., 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, has been reported in association with the increase in blood pressure. strategies to reduce the risk of hypertensive crisis: instruct patients to avoid foods and beverages with high tyramine content while being treated with tranylcypromine tablets and for 2 weeks after stopping tranylcypromine tablets [see drug interactions (7.2)] . careful evaluation of the benefits and risks of tranylcypromine tablets therapy is necessary in 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. in all patients taking tranylcypromine tablets, 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 tranylcypromine tablets, other drugs, foods or beverages suspected to contribute to the hypertensive crisis immediately [see drug interactions (7.1, 7.2)] . patients with severe elevations in blood pressure (e.g., 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. however, additional measures to control the causes of hyperthermia (psychomotor agitation, increased neuromuscular activity, persistent seizures) may be required. h y p er tension clinically significant increases in blood pressure have also been reported after the administration of maois, including tranylcypromine tablets, in patients not ingesting tyramine-rich foods or beverages. assess blood pressure before prescribing tranylcypromine tablets and closely monitor blood pressure in all patients taking tranylcypromine tablets 5.3 serotonin syndrome the development of a potentially life-threatening serotonin syndrome has been 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 the serotonin syndrome may include mental status changes (e.g., agitation, hallucinations, delirium, coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia; with possible rapid fluctuations of vital signs), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyper-reflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). fatal outcome of serotonin syndrome has been reported, including in patients who had been treated with tranylcypromine tablets. in some cases of an interaction between tranylcypromine tablets and ssris or snris, the features of the syndrome resembled neuroleptic malignant syndrome. the concomitant use, or use in rapid succession, of tranylcypromine tablets 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, tranylcypromine tablets must be discontinued as soon as possible before initiating treatment with the other agent. treatment with tranylcypromine tablets and any concomitant serotonergic agents should be discontinued immediately if the above events occur, and supportive symptomatic treatment should be initiated. 5.4 activation of mania or hypomania in patients with bipolar disorder, treating a depressive episode with tranylcypromine tablets or another antidepressant may precipitate a mixed/manic episode. prior to initiating treatment with tranylcypromine tablets, screen patients for any personal or family history of bipolar disorder, mania, or hypomania. 5.5 hypotension hypotension, including postural hypotension, has been observed during therapy with tranylcypromine tablets. at doses above 30 mg daily, postural hypotension is a major adverse reaction and may 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 tranylcypromine tablets. dosage increases should be made more gradually in patients with a tendency toward hypotension and/or postural hypotension (e.g., elderly patients) [see dosage and administration (2.2) and use in specific populations (8.5)] . such patients should be closely observed for postural changes in blood pressure throughout treatment. also, when tranylcypromine tablets are used concomitantly with other agents known to cause hypotension, the possibility of additive hypotensive effects should be considered [see drug interactions (7.1)] . postural hypotension may be relieved by having patients lie down until blood pressure returns to normal. 5.6 hypotension and hypertension during anesthesia and perioperative care it is recommended that tranylcypromine tablets 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 the use of agents that are contraindicated for concomitant use with tranylcypromine tablets. carefully consider the risk of agents and techniques that increase the risk for hypotension (e.g., epidural or spinal anesthesia) or other adverse reactions to tranylcypromine tablets (e.g., hypertension associated with the use of vasoconstrictors in local anesthetics). 5.7 need for emergency treatment with contraindicated drugs if in the absence of therapeutic alternatives emergency treatment with a contraindicated product (e.g., linezolid, intravenous methylene blue, direct-acting sympathomimetic drugs such as epinephrine) becomes necessary and cannot be delayed, discontinue tranylcypromine tablets as soon as possible before initiating treatment with the other product and monitor closely for adverse reactions [see drug interactions (7.1)]. 5.8 discontinuation syndrome abrupt discontinuation or dosage reduction of tranylcypromine tablets 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 (e.g. 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 tranylcypromine tablets. a gradual reduction in the dose rather than abrupt cessation is recommended whenever possible [see dosage and administration (2.3) and adverse reactions (6)] . 5.9 risk of clinically significant adverse reactions due to persistence of mao inhibition after discontinuation although excretion of tranylcypromine tablets is rapid, inhibition of mao may persist up to 10 days following discontinuation. this should be taken into account when considering the use of potentially interacting substances or the consumption of tyramine-rich food or beverages [see drug interactions (7.4)] , or when interpreting adverse reactions observed after discontinuation of tranylcypromine tablets. care should be taken to differentiate symptoms of persistent mao inhibition from withdrawal symptoms [see drug abuse and dependence (9.3)] . 5.10 hepatotoxicity hepatitis and elevated aminotransferases have been reported in association with tranylcypromine tablets administration. patients should be monitored accordingly. tranylcypromine tablets should be discontinued in patients who develop signs and symptoms of hepatotoxicity. sedation has occurred in tranylcypromine tablet-treated patients with cirrhosis. patients with cirrhosis receiving tranylcypromine tablets should be monitored for possible increased risks of central nervous system adverse reactions, such as excessive drowsiness. 5.11 seizures seizures have been reported with tranylcypromine tablets withdrawal after abuse, and with overdose. patients at risk for seizures should be monitored accordingly. 5.12 hypoglycemia in diabetic patients 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 tranylcypromine tablets and blood-glucose-lowering agents. a reduction of the dosage of such agents may be necessary [see drug interactions (7.1)]. 5.13 aggravation of coexisting symptoms of depression tranylcypromine tablets may aggravate coexisting symptoms in depression, such as anxiety and agitation. 5.14 adverse effects on the ability to drive and operate machinery some tranylcypromine tablets adverse reactions (e.g., 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 tranylcypromine tablets therapy does not impair their ability to engage in such activities.

itching to or from other antidepressants switching from contraindicated antidepressants to tranylcypromine tablets after stopping treatment with contraindicated antidepressants, a time period of 4 to 5 half-lives of the other antidepressant or any active metabolite should elapse before starting treatment with tranylcypromine tablets. after stopping treatment with an mao inhibitor antidepressant, a time period of at least one week or 4 to 5 half-lives of the other mao inhibitor (whichever is longer) should elapse before starting treatment with tranylcypromine tablets to reduce the risk of additive effects [see contraindications (4.1) and drug interactions (7.1)]. switching from tranylcypromine tablets to other maois or contraindicated antidepressants after stopping tranylcypromine tablets treatment, at least one week should elapse before starting another maoi (intended to treat mdd) or other contraindicated antidepressants. refer to the prescribing information of the subsequently used drug for product-specific advice on a medication-free interval [see contraindications (4.1) and drug interactions (7.1)]. 2.3 discontinuing treatment withdrawal effects, including delirium, have been reported with abrupt discontinuation of tranylcypromine tablets therapy. higher daily doses and longer duration of use appear to be associated with a higher risk of withdrawal effects. consider discontinuing tranylcypromine tablets therapy by slow, gradual dosage reduction [see warnings and precautions (5.8) and drug abuse and dependence (9.3)]. 2.4 screen for bipolar disorder and elevated blood pressure prior to starting tranylcypromine tablets prior to initiating treatment with tranylcypromine tablets: screen patients for a history of mania [see warnings and precautions (5.4)]. measure blood pressure [see warnings and precautions (5.2, 5.5)].

e warnings and precautions (5.14)] because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. based on clinical trial data, the most common adverse reactions to tranylcypromine were dry mouth, dizziness, insomnia, sedation, and headache (>30%) and overexcitement, constipation, blurred vision, and tremor (>10%). the following adverse reactions have been identified in clinical trials or during postapproval use of tranylcypromine tablets: b lood and lymphatic system disorders: agranulocytosis, leukopenia, thrombocytopenia, anemia e ndocrine disorders: impaired water excretion compatible with the syndrome of inappropriate secretion of antidiuretic hormone (siadh) me tabolism and nutrition disorders: significant anorexia, weight gain p sychiatric disorders: excessive stimulation/overexcitement, manic symptoms/hypomania, agitation, insomnia, anxiety, confusion, disorientation, loss of libido nervous system disorders: dizziness, restlessness/akathisia, akinesia, ataxia, myoclonic jerks, tremor, hyper-reflexia, muscle spasm, paresthesia, numbness, memory loss, sedation, drowsiness, dysgeusia, headaches (without blood pressure elevation) ey e disorders: blurred vision, nystagmus e ar and labyrinth disorders: tinnitus cardiac disorders: tachycardia, palpitations v ascular disorders: hypertensive crisis, hypertension, hypotension (including postural hypotension with syncope) g astrointestinal disorders: diarrhea, constipation, nausea, abdominal pain, dry mouth, fissuring in corner of mouth he patobiliary disorders: hepatitis, elevated aminotransferases skin and subcutaneous tissue disorders: localized scleroderma, flare-up of cystic acne, urticaria, rash, alopecia, sweating re nal and urinary disorders: urinary retention, urinary incontinence, urinary frequency re productive system and breast disorders: impotence, delayed ejaculation general disorders and administration site conditions: edema, chills, weakness, fatigue/lethargy most common adverse reactions (>10%) were dry mouth, dizziness, insomnia, sedation, headache, overexcitement, constipation, blurred vision, and tremor (6) to report suspected adverse reactions, contact novitium pharma llc at 1-855-204-1431 or fda at 1-800-fda-1088 or www.fda.gov/medwatch .

ent with an mao inhibitor antidepressant, a time period of at least 1 week or 4 to 5 half-lives of the other mao inhibitor (whichever is longer) should elapse before starting treatment with tranylcypromine tablets because of the risk for clinically significant adverse reactions after discontinuation due to persistent mao inhibition [see dosage and administration (2.2), warnings and precautions (5.9)] . this period can be several weeks long (e.g., a minimum of 5 weeks for fluoxetine given fluoxetine’s long half-life). refer to the prescribing information of the contraindicated product for relevant information. t ime to start contraindicated drug after discontinuation of tranylcypromine tablets the potential for interactions persists after discontinuation of tranylcypromine tablets until mao activity has sufficiently recovered. inhibition of mao may persist up to 10 days following discontinuation [see warnings and precautions (5.9)] . after stopping tranylcypromine tablets, at least 1 week should elapse before starting another maoi (intended to treat mdd) or other contraindicated antidepressants. refer to the prescribing information of any agent considered for subsequent use for recommendations on the duration of a waiting period after discontinuation of a mao inhibitor. if in the absence of therapeutic alternatives and emergency treatment with a contraindicated drug (e.g., linezolid, intravenous methylene blue, direct-acting sympathomimetic drugs such as epinephrine) becomes necessary and cannot be delayed, discontinue tranylcypromine tablets as soon as possible before initiating treatment with the other agent, and monitor closely for adverse reactions. table 3: clinically significant drug interactions with drug classes* p r oduct c linical comment on concomitant usea p r e dominant effect/risk [hypertensive reaction (hr)b or serotonin syndrome (ss)c] agents with blood pressure-reducing effects use with cautiond hypotensione non-selective h1 receptor antagonists contraindicateda increased anticholinergic effects beta-adrenergic blockers (see also agents or procedures with blood pressure-reducing effects) use with cautiond more pronounced bradycardia, postural hypotensione blood glucose-lowering agents dosage reduction of such agents may be necessary. monitor blood glucose. excessive reduction of blood glucose (additive effect)f cns depressant agents (including opioids, alcohol, sedatives, hypnotics) use with cautiond increased cns depression dietary supplements containing sympathomimetics contraindicateda antidepressants including but not limited to: other maois (e.g., linezolid, intravenous methylene blue, selective maois) selective serotonin reuptake inhibitors (ssris) and serotonin and norepinephrine reuptake inhibitors (snris) tricyclic antidepressants amoxapine, bupropion, maprotiline, nefazodone, trazodone, vilazodone, vortioxetine contraindicateda ss for all antidepressants for maois, increased mao inhibition and risk of adverse reactions, ss, and hrg amphetamines and methylphenidates andderivatives contraindicateda hr sympathomimetic drugs** contraindicateda hr; including risk of intracerebral hemorrhage triptans contraindicateda ss * some drugs in these groups may also be listed in table 4 below. ** sympathomimetic drugs include amphetamines as well as cold, hay fever or weight-reducing products that contain vasoconstrictors such as pseudoephedrine, phenylephrine, and ephedrine) a [s ee contraindications (4.1)]; b [s ee warnings and precautions (5.2)]; c [ s ee warnings and precautions (5.3)] d if not otherwise specified in this table, consider avoiding concomitant use (see also information on medication-free intervals, use agent at the lowest appropriate dosage, monitor for effects of the interaction, advise the patient to report potential effects). e [s ee warnings and precautions (5.5)]; f [s ee warnings and precautions (5.14)]; g [s ee overdosage (10.1)] table 4: clinically significant drug interactions with individual products* p r oduct c linical comment on concomitant usea p r e dominant effect/risk [hypertensive reaction (hr)b or serotonin syndrome (ss)c] altretamine use with cautiond orthostatic hypotensione buspirone contraindicateda hr carbamazepine contraindicateda ss chlorpromazine use with cautiond hypotensive effectse cyclobenzaprine contraindicateda ss dextromethorphan contraindicateda ss; psychosis, bizarre behavior dopamine contraindicateda hr droperidol use with cautiond qt interval prolongation entacapone use with cautiond hr fentanyl use with cautiond ss hydroxytryptophan contraindicateda ss levodopa contraindicateda hr lithium use with cautiond ss meperidine contraindicateda ss methadone use with cautiond ss methyldopa contraindicateda hr metoclopramide use with cautiond hr/ss mirtazapine contraindicateda ss oxcarbazepine use with cautiond because of close structural relationship with tricyclic antidepressants ss rasagiline contraindicateda hr reserpine contraindicateda hr s-adenosyl-l-methionine (sam-e) contraindicateda ss tapentadol contraindicateda hr/ss tetrabenazine contraindicateda hr tolcapone use with cautiond hr tramadol use with cautiond ss; increased seizure risk tryptophan contraindicateda ss * some drugs in this table may also belong to groups listed in table 3 above, and may be associated with additional interactions. a [s ee contraindications (4.1)]; b [s ee warnings and precautions (5.3)]; c [ s ee warnings and precautions (5.7)] d if not otherwise specified in this table, consider avoiding concomitant use (see also information on medication-free intervals, use agent at the lowest appropriate dose, monitor for effects of the interaction, advise the patient to report potential effects, and be prepared to discontinue the agent and treat effects of the interaction e [s ee warnings and precautions (5.5) 7.2 tyramine-containing foods and beverages tranylcypromine tablets inhibits intestinal mao, which is responsible for the catabolism of tyramine in food and beverages. as a result of this inhibition, large amounts of tyramine may enter the systemic circulation and precipitate a sudden elevation in blood pressure or hypertensive crisis [see warnings and precautions (5.2)] . instruct tranylcypromine tablet-treated patients to avoid foods and beverages with significant tyramine content during treatment with tranylcypromine tablets or within 2 weeks of stopping treatment (see table 5 for a list of food and beverages containing significant amounts of tyramine). table 5: foods and beverages with and without significant amounts of tyramine c lass of f ood or beverage tyramine-rich foods and beverages to avoid acce ptable foods and dr inks, containing no or little tyramine meat, poultry, and fish air dried, aged and fermented meats, sausages and salamis (including cacciatore, hard salami and mortadella); pickled herring; and any spoiled or improperly stored meat, poultry, and fish (e.g., foods that have undergone changes in coloration, odor, or become moldy); spoiled or improperly stored animal livers fresh meat, poultry, and fish, including fresh processed meats (e.g., lunch meats, hot dogs, breakfast sausage, and cooked sliced ham) vegetables broad bean pods (fava bean pods) all other vegetables dairy aged cheeses processed cheeses, mozzarella, ricotta cheese, cottage cheese, and yogurt beverages all varieties of tap beer and beers that have not been pasteurized so as to allow for ongoing fermentation and excessive amounts of caffeine. concomitant use of alcohol with tranylcypromine tablets is not recommended. (bottled and canned beers and wines contain little or no tyramine.) other concentrated yeast extract (e.g., marmite), sauerkraut, most soybean products (including soy sauce and tofu), otc supplements containing tyramine, and chocolate brewer’s yeast, baker’s yeast, soy milk, commercial chain restaurant pizzas prepared with cheeses low in tyramine

(e.g., epidural anesthesia) should be taken into account in women who have received tranylcypromine tablets [see warnings and precautions (5.6) and drug interactions (7.1)]. 8.2 lactation risk summary tranylcypromine is present in human milk. there is no available information on the effects of tranylcypromine on milk production. there is no available information on the effects of tranylcypromine on a breastfed child; however, because of the potential for serious adverse reactions in a breastfed infant, advise nursing women to discontinue breastfeeding during treatment with tranylcypromine tablets. 8.4 pediatric use safety and effectiveness of tranylcypromine tablets in the pediatric population have not been established. all risks associated with the use of tranylcypromine tablets, including the risk of suicidal thoughts and behavior, apply to adults and pediatric patients [see boxed warning and warnings and precautions (5)]. 8.5 geriatric use older patients may be at greater risk of postural hypotension and other serious adverse reactions [see warnings and precautions (5)] . in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

ould be taken into account in women who have received tranylcypromine tablets [see warnings and precautions (5.6) and drug interactions (7.1)].

and drug interactions (7.1)] warn the patient not to take concomitant medications, whether prescription or over-the-counter drugs, or dietary supplements without prior consultation with a health care provider able to provide advice on the potential for interactions. explain to the patient that some other drugs may require a medication-free interval even after discontinuation of tranylcypromine tablets. advise the patient to inform other physicians, pharmacists, and dentists about the treatment with tranylcypromine tablets. interaction with foods and beverages [see contraindications (4.1) and drug interactions (7.2)] warn the patient to avoid tyramine-rich foods and beverages. advise the patient to avoid eating foods if storage conditions or freshness is unknown and to be cautious of foods of unknown age or composition even if refrigerated. hypotension advise the patient to report any symptoms of hypotension in the initial phase of treatment to the healthcare provider, because occurrence of such symptoms may require discontinuation [see dosage and administration (2.1) and warnings and precautions (5.5)] . withdrawal symptoms warn the patient not to stop tranylcypromine tablets treatment abruptly, as withdrawal symptoms may occur and that the effect of tranylcypromine tablets may continue even after discontinuation [see warnings and precautions (5.8, 5.9)]. aggravation of coexisting symptoms of depression inform the patient that tranylcypromine tablets may aggravate coexisting symptoms in depression, such as anxiety and agitation and instruct them to contact their healthcare provider if they experience such symptoms [see warnings and precautions (5.13)]. effects on ability to drive or use machinery [see warnings and precautions (5.14)] warn the patient about the possible adverse reactions that can impair the performance of potentially hazardous tasks such as driving a car or operating machinery. tell the patient not to operate hazardous machinery and automobiles until they are reasonably certain that their ability to engage in such activities is not impaired. all trademarks are the property of their respective owners. manufactured by: novitium pharma llc 70 lake drive, east windsor new jersey 08520. issued: 05/2021 lb4346-00