WARNINGS AND PRECAUTIONS SECTION.


5 WARNINGS AND PRECAUTIONS. Activation of Mania/Hypomania: May be precipitated by antidepressant treatment in patients with bipolar disorder. Screen patients prior to treatment (5.4) Hypotension (including syncope): Monitor patients and adjust tranylcypromine sulfate tablets dosage or concomitant medication as necessary (5.5) Hypotension and Hypertension during Anesthesia and Perioperative Care: If possible, discontinue tranylcypromine sulfate tablets prior to elective surgery (5.6) Hepatitis and Elevated Liver Enzymes: Monitor accordingly (5.10) Activation of Mania/Hypomania: May be precipitated by antidepressant treatment in patients with bipolar disorder. Screen patients prior to treatment (5.4) Hypotension (including syncope): Monitor patients and adjust tranylcypromine sulfate tablets dosage or concomitant medication as necessary (5.5) Hypotension and Hypertension during Anesthesia and Perioperative Care: If possible, discontinue tranylcypromine sulfate tablets prior to elective surgery (5.6) Hepatitis and Elevated Liver Enzymes: Monitor accordingly (5.10) 5.1 Suicidal Thoughts and Behaviors in Adolescents and Young Adults. In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients. There was considerable variation in risk of 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 PatientsAge RangeDrug-Placebo Difference in Number of Patients of Suicidal Thoughts or Behaviors per 1000 Patients Treated Increases Compared to Placebo<18 years old14 additional patients18-24 years old5 additional patients Decreases Compared to Placebo25-64 years old1 fewer patient>=65 years old6 fewer patientsIt 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 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 sulfate tablets in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors. 5.2 Hypertensive Crisis and Hypertension. Hypertensive Crisis MAOIs, including tranylcypromine sulfate tablets, have been associated with hypertensive crises caused by the ingestion of foods or beverages with 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 hypertensive crisis constitutes hypertensive emergency, which requires immediate attention to prevent serious complications or fatal outcome. These emergencies are characterized by severe hypertension (e.g., with 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 sulfate tablets and for weeks after stopping tranylcypromine sulfate tablets [see Drug Interactions (7.2)].Careful evaluation of the benefits and risks of tranylcypromine sulfate 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, andA history of headaches that can mask the occurrence of headaches as prodromal of hypertensive crisis.In all patients taking tranylcypromine sulfate 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 manifestation of hypertensive crisis, such as palpitations or headaches, and patients should be evaluated immediately. Discontinue tranylcypromine sulfate 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. Hypertension Clinically significant increases in blood pressure have also been reported after the administration of MAOIs, including tranylcypromine sulfate tablets, in patients not ingesting tyramine-rich foods or beverages. Assess blood pressure before prescribing tranylcypromine sulfate tablets and closely monitor blood pressure in all patients taking tranylcypromine sulfate tablets.. Hypertension or confirmed or suspected cerebrovascular or cardiovascular disorders that constitute an increased risk for complications from severe hypertension, and. history of headaches that can mask the occurrence of headaches as prodromal of hypertensive crisis.. 5.3 Serotonin Syndrome. The development of 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. Johns 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 sulfate tablets. In some cases of an interaction between tranylcypromine sulfate tablets and SSRIs or SNRIs, the features of the syndrome resembled neuroleptic malignant syndrome. The concomitant use, or use in rapid succession, of tranylcypromine sulfate 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 sulfate tablets must be discontinued as soon as possible before initiating treatment with the other agent. Treatment with tranylcypromine sulfate 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 depressive episode with tranylcypromine sulfate tablets or another antidepressant may precipitate mixed/manic episode. Prior to initiating treatment with tranylcypromine sulfate 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 sulfate tablets. At doses above 30 mg daily, postural hypotension is 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 sulfate tablets. Dosage increases should be made more gradually in patients with 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 sulfate 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 sulfate 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 sulfate 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 sulfate 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 contraindicated product (e.g., linezolid, intravenous methylene blue, direct-acting sympathomimetic drugs such as epinephrine) becomes necessary and cannot be delayed, discontinue tranylcypromine sulfate 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 sulfate 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 sulfate tablets. 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 sulfate tablet 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 (7.2)], or when interpreting adverse reactions observed after discontinuation of tranylcypromine sulfate 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 sulfate tablets administration. Patients should be monitored accordingly. Tranylcypromine sulfate tablets should be discontinued in patients who develop signs and symptoms of hepatotoxicity. Sedation has occurred in tranylcypromine sulfate tablets-treated patients with cirrhosis. Patients with cirrhosis receiving tranylcypromine sulfate 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 sulfate 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 sulfate tablets and blood-glucose-lowering agents. reduction of the dosage of such agents may be necessary [see Drug Interactions (7.1 )] 5.13 Aggravation of Coexisting Symptoms of Depression. Tranylcypromine sulfate 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 sulfate tablets adverse reactions (e.g., hypotension, faintness, drowsiness, confusion, disorientation) can impair patients 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 sulfate tablets therapy does not impair their ability to engage in such activities.

ABUSE SECTION.


9.2 Abuse. Abuse of tranylcypromine sulfate tablets has been reported. Some of these patients had history of previous substance abuse. The potential for abuse and the increased risk of serious adverse reactions with higher doses should be taken into account when considering the use of tranylcypromine sulfate tablets for patients at increased risk for substance abuse.

ADVERSE REACTIONS SECTION.


6 ADVERSE REACTIONS. The following adverse reactions are described in greater detail in other sections: Suicidal thoughts and behaviors [see Warnings and Precautions (5.1)] Hypertensive crisis and hypertension [see Warnings and Precautions (5.2)] Serotonin syndrome [see Warnings and Precautions (5.3)] Activation of mania/hypomania [see Warnings and Precautions (5.4)] Hypotension [see Warnings and Precautions (5.5)] Hypotension and hypertension during anesthesia and perioperative care [see Warnings and Precautions (5.6)] Discontinuation syndrome [see Warnings and Precautions (5.8)] Persistence of MAO inhibition after discontinuation see Warnings and Precautions (5.9)] Hepatotoxicity [see Warnings and Precautions (5.10)] Seizures[see Warnings and Precautions (5.11)] Hypoglycemia in diabetic patients [see Warnings and Precautions (5.12)] Aggravation of coexisting symptoms of depression [see Warnings and Precautions (5.13)] Adverse effects on the ability to drive and operate machinery [see Warnings and Precautions (5.14)] Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of 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 overexctextent, constipation, blurred vision, and tremor (>10%). The following adverse reactions have been identified in clinical trials or during post approval use of tranylcypromine sulfate tablets: Blood and lymphatic system disorders: agranulocytosis, leukopenia, thrombocytopenia, anemia Endocrine disorders: impaired water excretion compatible with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) Metabolism and nutrition disorders: significant anorexia, weight gain Psychiatric disorders: excessive stimulation/overexctextent, 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) Eye disorders: blurred vision, nystagmus Ear and labyrinth disorders: tinnitus Cardiac disorders: tachycardia, palpitations Vascular disorders: hypertensive crisis, hypertension, hypotension (including postural hypotension with syncope) Gastrointestinal disorders: diarrhea, constipation, nausea, abdominal pain, dry mouth, fissuring in corner of mouth Hepatobiliary disorders: hepatitis, elevated aminotransferases Skin and subcutaneous tissue disorders: localized scleroderma, flare-up of cystic acne, urticaria, rash, alopecia, sweating Renal and urinary disorders: urinary retention, urinary incontinence, urinary frequency Reproductive system and breast disorders: impotence, delayed ejaculation General disorders and administration site conditions: edema, chills, weakness, fatigue/lethargy. Suicidal thoughts and behaviors [see Warnings and Precautions (5.1)] Hypertensive crisis and hypertension [see Warnings and Precautions (5.2)] Serotonin syndrome [see Warnings and Precautions (5.3)] Activation of mania/hypomania [see Warnings and Precautions (5.4)] Hypotension [see Warnings and Precautions (5.5)] Hypotension and hypertension during anesthesia and perioperative care [see Warnings and Precautions (5.6)] Discontinuation syndrome [see Warnings and Precautions (5.8)] Persistence of MAO inhibition after discontinuation see Warnings and Precautions (5.9)] Hepatotoxicity [see Warnings and Precautions (5.10)] Seizures[see Warnings and Precautions (5.11)] Hypoglycemia in diabetic patients [see Warnings and Precautions (5.12)] Aggravation of coexisting symptoms of depression [see Warnings and Precautions (5.13)] Adverse effects on the ability to drive and operate machinery [see Warnings and Precautions (5.14)] Most common adverse reactions (>10%) were dry mouth, dizziness, insomnia, sedation, headache, overexctextent, constipation, blurred vision, and tremor (6) To report SUSPECTED ADVERSE REACTIONS, contact Actavis at 1-800-432-8534 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

BOXED WARNING SECTION.


WARNING:SUICIDAL THOUGHTS AND BEHAVIORS and HYPERTENSIVE CRISIS WITH SIGNIFICANT TYRAMINE USE. Suicidal Thoughts and Behaviors Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors [see Warnings and Precautions (5.1)]. Tranylcypromine sulfate tablets are not approved for use in pediatric patients[see Use in Specific Populations (8.4)]. Hypertensive Crisis with Significant Tyramine Use Excessive consumption of foods or beverages with significant tyramine content or the use of certain drugs with tranylcypromine sulfate tablets or after tranylcypromine sulfate tablets discontinuation can precipitate hypertensive crisis. Monitor blood pressure and allow for medication-free intervals between administration of tranylcypromine sulfate tablets and interacting drugs. Instruct patients to avoid ingestion of foods and beverages with high tyramine content [see Warnings and Precautions (5.2) and Drug Interactions (7.1, 7.2)]. WARNING: SUICIDAL THOUGHTS AND BEHAVIORS and HYPERTENSIVE CRISIS WITH SIGNIFICANT TYRAMINE USESee full prescribing information for complete boxed warning.Increased risk of suicidal thoughts and behavior in pediatric and young adult patients taking antidepressants. Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors. Tranylcypromine sulfate tablets are not approved for use in pediatric patients. (5.1,8.4) Excessive consumption of foods or beverages with significant tyramine content or certain drugs can precipitate hypertensive crisis. Monitor blood pressure, allow for medication free intervals, and advise patients to avoid foods and beverages with high tyramine content. (5.2, 7.1, 7.2). Increased risk of suicidal thoughts and behavior in pediatric and young adult patients taking antidepressants. Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors. Tranylcypromine sulfate tablets are not approved for use in pediatric patients. (5.1,8.4) Excessive consumption of foods or beverages with significant tyramine content or certain drugs can precipitate hypertensive crisis. Monitor blood pressure, allow for medication free intervals, and advise patients to avoid foods and beverages with high tyramine content. (5.2, 7.1, 7.2).

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.


13.1 Carcinogenesis Mutagenesis Impairment Of Fertility. No carcinogenesis, mutagenesis, or fertility impairment studies were conducted.

CLINICAL PHARMACOLOGY SECTION.


12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. The mechanism of action of tranylcypromine sulfate tablets as an antidepressant is not fully understood, but is presumed to be linked to potentiation of monoamine neurotransmitter activity in the central nervous system (CNS) resulting from its irreversible inhibition of the enzyme monoamine oxidase (MAO).. 12.2 Pharmacodynamics. Although tranylcypromine is eliminated in 24 hours, recovery MAO activity takes up to to days [see Warnings and Precautions (5.9)].

CONTRAINDICATIONS SECTION.


4 CONTRAINDICATIONS. Concomitant use or use in rapid succession with other MAOIs; selective serotonin reuptake inhibitors; serotonin and norepinephrine reuptake inhibitors; tricyclic antidepressants; sympathomimetic drugs; and numerous other drugs. See Full Prescribing Information for the full list of contraindicated products (4.1, 7.1)Pheochromocytoma, other catecholamine-releasing paraganglioma (4.2). Concomitant use or use in rapid succession with other MAOIs; selective serotonin reuptake inhibitors; serotonin and norepinephrine reuptake inhibitors; tricyclic antidepressants; sympathomimetic drugs; and numerous other drugs. See Full Prescribing Information for the full list of contraindicated products (4.1, 7.1). Pheochromocytoma, other catecholamine-releasing paraganglioma (4.2). 4.1 Combination with Certain Drugs. Concomitant use of tranylcypromine sulfate tablets or use in rapid succession with the products in Table is contraindicated. Such use may cause severe or life-threatening reactions such as hypertensive crises or serotonin syndrome [see Drug Interactions (7.1)].Medication-free periods between administration of tranylcypromine sulfate tablets and contraindicated agents are recommended see Dosage and Administration (2.2) and Drug Interactions (7.1) ]. Table 1: Products Contraindicated with the Use of Tranylcypromine Sulfate Tablets Drug ClassesNon-selective H1 receptor antagonistsAntidepressants including but not limited to: Other monoamine oxidase inhibitors (MAOIs)Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs)Tricyclic antidepressantsOther antidepressants (e.g., amoxapine, bupropion, maprotiline, nefazodone, trazodone, vilazodone, vortioxetine) Amphetamines and methylphenidates and derivativesSympathomimetic 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)TriptansIndividual Drugs (not included in the above classes)buspironelevodopas-adenosyl-L-methionine (SAM-e)carbamazepinemeperidinetapentadolcyclobenzaprinemethyldopatetrabenazinedextromethorphanmilnaciprantryptophandopaminerasagilinehydroxytryptophanreserpine. Other monoamine oxidase inhibitors (MAOIs). Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs). Tricyclic antidepressants. Other antidepressants (e.g., amoxapine, bupropion, maprotiline, nefazodone, trazodone, vilazodone, vortioxetine). 4.2 Pheochromocytoma and Catecholamine-Releasing Paragangliomas. Tranylcypromine sulfate tablets are contraindicated in the presence of pheochromocytoma or other catecholamine-releasing paragangliomas because such tumors secrete pressor substances and can lead to hypertensive crisis [see Warnings and Precautions (5.3)].

DEPENDENCE SECTION.


9.3 Dependence. Dependence, evidenced by precipitation of withdrawal effects following abrupt discontinuation of tranylcypromine sulfate tablets has been reported. Reported withdrawal effects included delirium (even with low daily doses), restlessness, anxiety, confusion, hallucinations, headache, weakness, diarrhea, and/or rapid relapse into depression. Thrombocytopenia and liver enzyme increases have also been observed in association with tranylcypromine sulfate tablets withdrawal from high doses [see Overdosage (10.1)] Withdrawal effects have appeared within to days of discontinuation and have persisted for several weeks after discontinuation. The use of daily doses greater than recommended and longer duration of use appear to be associated with higher risk of withdrawal effects. Monitor for withdrawal effects for at least week after discontinuation. Consider discontinuing tranylcypromine sulfate tablet therapy by slow, gradual dose reduction see Dosage and Administration (2.3)].

DESCRIPTION SECTION.


11 DESCRIPTION. Tranylcypromine sulfate, the active ingredient of tranylcypromine sulfate tablets, is non-hydrazine MAOI. The chemical name is (+-)-trans-2-phenylcyclopropylamine sulfate (2:1). The molecular formula is (C9H11N)2oH2SO4 and its molecular weight is 364.46. The structural formula is:Tranylcypromine sulfate tablets film-coated tablets are intended for oral administration. Each round, rose-red tablet is debossed on one side with the product name PARNATE and SB and contains tranylcypromine sulfate equivalent to 10 mg of tranylcypromine.Inactive ingredients consist of microcrystalline cellulose, anhydrous citric acid, croscarmellose sodium, D&C Red No. 7, FD&C Blue No. 2, FD&C Yellow No. 6, gelatin, lactose, magnesium stearate, talc, titanium dioxide, carnauba wax, polyethylene glycol 400 and 8000, and hypromellose.. structure.

DOSAGE & ADMINISTRATION SECTION.


2 DOSAGE ADMINISTRATION. Recommended daily dosage is 30 mg in divided doses (2.1) If no adequate response, increase dosage in increments of 10 mg per day every to weeks to maximum dosage of 30 mg twice daily (60 mg per day).Consider more gradual dosage increases in patients at risk for hypotension (2.1) Consider discontinuing tranylcypromine sulfate tablets therapy gradually because of the risk for withdrawal effects (2.3, 5.8, 9.3)Switching from or to other MAOIs or other antidepressants: See full prescribing information for instructions (2.2, 7.1) Recommended daily dosage is 30 mg in divided doses (2.1) If no adequate response, increase dosage in increments of 10 mg per day every to weeks to maximum dosage of 30 mg twice daily (60 mg per day).Consider more gradual dosage increases in patients at risk for hypotension (2.1) Consider discontinuing tranylcypromine sulfate tablets therapy gradually because of the risk for withdrawal effects (2.3, 5.8, 9.3). Switching from or to other MAOIs or other antidepressants: See full prescribing information for instructions (2.2, 7.1) 2.1 Recommended Dosage. Tranylcypromine sulfate tablets are for oral use. The recommended dosage is 30 mg per day (in divided doses). If patients do not have an adequate response, increase the dosage in increments of 10 mg per day every to weeks to maximum 30 mg twice daily (60 mg per day). Dosage increases should be made more gradually in patients at risk for hypotension (e.g., geriatric patients) [see Warnings and Precautions (5.5)]. 2.2 Switching to or from Other Antidepressants. Switching from Contraindicated Antidepressants to Tranylcypromine Sulfate Tablets After stopping treatment with contraindicated antidepressants, time period of to half-lives of the other antidepressant or any active metabolite should elapse before starting treatment with tranylcypromine sulfate tablets. After stopping treatment with an MAO inhibitor antidepressant, time period of at least one week or to half-lives of the other MAO inhibitor (whichever is longer) should elapse before starting treatment with tranylcypromine sulfate tablets to reduce the risk of additive effects [see Contraindications (4.1)and Drug Interactions (7.1)]. Switching from Tranylcypromine Sulfate Tablets to Other MAOIs or Contraindicated Antidepressants After stopping tranylcypromine sulfate 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 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 sulfate tablets therapy. Higher daily doses and longer duration of use appear to be associated with higher risk of withdrawal effects. Consider discontinuing tranylcypromine sulfate 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 Sulfate Tablets. Prior to initiating treatment with tranylcypromine sulfate tablets:Screen patients for history of mania [see Warnings and Precautions(5.4)]. Measure blood pressure [see Warnings and Precautions (5.2, 5.5)]. Screen patients for history of mania [see Warnings and Precautions(5.4)]. Measure blood pressure [see Warnings and Precautions (5.2, 5.5)].

DOSAGE FORMS & STRENGTHS SECTION.


3 DOSAGE FORMS STRENGTHS. Tablets containing tranylcypromine sulfate equivalent to 10 mg tranylcypromine are round, rose-red, film-coated, and debossed on one side with PARNATE and SB.. Tablets: 10 mg.

DRUG ABUSE AND DEPENDENCE SECTION.


9 DRUG ABUSE AND DEPENDENCE. 9.2 Abuse. Abuse of tranylcypromine sulfate tablets has been reported. Some of these patients had history of previous substance abuse. The potential for abuse and the increased risk of serious adverse reactions with higher doses should be taken into account when considering the use of tranylcypromine sulfate tablets for patients at increased risk for substance abuse.. 9.3 Dependence. Dependence, evidenced by precipitation of withdrawal effects following abrupt discontinuation of tranylcypromine sulfate tablets has been reported. Reported withdrawal effects included delirium (even with low daily doses), restlessness, anxiety, confusion, hallucinations, headache, weakness, diarrhea, and/or rapid relapse into depression. Thrombocytopenia and liver enzyme increases have also been observed in association with tranylcypromine sulfate tablets withdrawal from high doses [see Overdosage (10.1)] Withdrawal effects have appeared within to days of discontinuation and have persisted for several weeks after discontinuation. The use of daily doses greater than recommended and longer duration of use appear to be associated with higher risk of withdrawal effects. Monitor for withdrawal effects for at least week after discontinuation. Consider discontinuing tranylcypromine sulfate tablet therapy by slow, gradual dose reduction see Dosage and Administration (2.3)].

DRUG INTERACTIONS SECTION.


7 DRUG INTERACTIONS. See Full Prescribing Information for list of products, foods and beverages that can interact with tranylcypromine sulfate tablets (7) 7.1 Clinically Significant Drug Interactions. Tables and lists drug classes and individual products, respectively, with potential for interaction with tranylcypromine sulfate tablets, describes the predominant observed or anticipated risks, and provides advice on concomitant use. Given serious adverse reactions with multiple agents, patients should avoid taking over-the-counter medications or dietary supplements without prior consultation with healthcare provider able to provide advice on the potential for interactions. Time to Start Tranylcypromine Sulfate Tablets after Discontinuation of Contraindicated DrugFor products that are contraindicated with tranylcypromine sulfate tablets, time period of to half-lives of the other product or any active metabolite should elapse before starting treatment with tranylcypromine sulfate tablets. After stopping treatment with an MAO inhibitor antidepressant, time period of at least week or to half-lives of the other MAO inhibitor (whichever is longer) should elapse before starting treatment with tranylcypromine sulfate 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., minimum of weeks for fluoxetine given fluoxetines long half-life). Refer to the prescribing information of the contraindicated product for relevant information.Time to Start Contraindicated Drug after Discontinuation of Tranylcypromine Sulfate Tablets The potential for interactions persists after discontinuation of tranylcypromine sulfate 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 sulfate tablets, at least 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 waiting period after discontinuation of MAO inhibitor. If in the absence of therapeutic alternatives and emergency treatment with contraindicated drug (e.g., linezolid, intravenous methylene blue, direct-acting sympathomimetic drugs such as epinephrine) becomes necessary and cannot be delayed, discontinue tranylcypromine sulfate tablets as soon as possible before initiating treatment with the other agent, and monitor closely for adverse reactions.Table Clinically Significant Drug Interactions with Drug Classes ProductClinical Comment on Concomitant Usea Predominant Effect/Risk[Hypertensive Reaction (HR)b or Serotonin Syndrome (SS)c]Agents with blood pressure-reducing effects Use with cautiondHypotensioneNon-selective H1 receptor antagonistsContraindicatedaIncreased anticholinergic effectsBeta-adrenergic blockers (see also agents or procedures with blood pressure-reducing effects) Use with the cautiondMore pronounced bradycardia, postural hypotensioneBlood glucose-lowering agentsDosage reduction of such agents may be necessary. Monitor blood glucose.Excessive reduction of blood glucose (additive effect)fCNS depressant agents (including opioids, alcohol, sedatives, hypnotics)Use with cautiondIncreased CNS depressionDietary supplements containing sympathomimeticsContraindicatedaAntidepressants 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 antidepressantsAmoxapine, bupropion, maprotiline, nefazodone, trazodone, vilazodone, vortioxetine ContraindicatedaSS for all antidepressants For MAOIs, increased MAO inhibition and risk of adverse reactions, SS, and HRg Amphetamines and methylphenidates and derivativesContraindicatedaHRSympathomimetic drugsContraindicatedaHR; Including risk of intracerebral hemorrhageTriptansContraindicatedaSS Some drugs in these groups may also be listed in Table below. Sympathomimetic drugs include amphetamines as well as cold, hay fever or weight-reducing products that contain vasoconstrictors such as pseudoephedrine, phenylephrine, and ephedrine) [See Contraindications (4.1)]; [See Warnings and Precautions (5.2)]; [ See Warnings and Precautions (5.3)] 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). [See Warnings and Precautions (5.5)]; [See Warnings and Precautions (5.14)]; [See Overdosage (10.1)] Table 4: Clinically Significant Drug Interactions with Individual Products ProductClinical Comment on Concomitant Usea Predominant Effect/Risk[Hypertensive Reaction (HR)b or Serotonin Syndrome (SS)c]AltretamineUse with cautiondOrthostatic hypotensioneBuspironeContraindicatedaHRCarbamazepineContraindicatedaSSChlorpromazineUse with cautiondHypotensive effectseCyclobenzaprineContraindicatedaSSDextromethorphanContraindicatedaSS; Psychosis, bizarre behaviorDopamineContraindicatedaHRDroperidolUse with cautiond QT interval prolongationEntacaponeUse with cautiond HRFentanylUse with cautiond SSHydroxytryptophanContraindicatedaSSLevodopaContraindicatedaHRLithiumUse with cautiond SSMeperidineContraindicatedaSSMethadoneUse with cautiondSSMethyldopaContraindicatedaHRMetoclopramideUse with cautiondHR/SSMirtazapineContraindicatedaSSOxcarbazepineUse with cautiond because of close structural relationship with tricyclic antidepressantsSSRasagilineContraindicatedaHRReserpineContraindicatedaHRS-adenosyl-L-methionine (SAM-e)ContraindicatedaSSTapentadolContraindicatedaHR/SSTetrabenazineContraindicatedaHRTolcaponeUse with cautiondHRTramadolUse with cautiondSS; Increased seizure riskTryptophanContraindicatedaSSSome drugs in this table may also belong to groups listed in Table above, and may be associated with additional interactions. a[See Contraindications (4.1)] ;b[See Warnings and Precautions (5.3)] c[See Warnings and Precautions (5.7)] dIf 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[See Warnings and Precautions (5.5)] 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. 7.2 Tyramine-Containing Foods and Beverages. Tranylcypromine sulfate tablets inhibit intestinal MAO, which is responsible for the catabolism of tyramine in food and beverages. As result of this inhibition, large amounts of tyramine may enter the systemic circulation and precipitate sudden elevation in blood pressure or hypertensive crisis [see Warnings and Precautions (5.2)].Instruct tranylcypromine sulfate tablets-treated patients to avoid foods and beverages with significant tyramine content during treatment with tranylcypromine sulfate tablets or within weeks of stopping treatment (see Table for list of food and beverages containing significant amounts of tyramine).Table 5: Foods and Beverages with and without Significant Amounts of TyramineClass of Food orBeverageTyramine-Rich Foods and Beverages to AvoidAcceptable Foods and Drinks, Containing No or Little TyramineMeat, 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 sulfate tabletsis 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 andtofu), OTC supplements containing tyramine, and chocolate Brewers yeast, bakers yeast, soy milk, commercial chain restaurant pizzas prepared with cheeses low in tyramine.

GERIATRIC USE SECTION.


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.

HOW SUPPLIED SECTION.


16 HOW SUPPLIED/STORAGE AND HANDLING. Tranylcypromine sulfate tablets (tranylcypromine) tablets are available as: 10 mg: film-coated, round, rose-red and debossed with the product name PARNATE on one side and SB on the other side containing tranylcypromine sulfate equivalent to 10 mg of tranylcypromine.Bottles of 100 tablets: NDC 0591-5590-01Store between 15 and 30C (59 and 86F). Dispense in tight, light resistant container. 10 mg: film-coated, round, rose-red and debossed with the product name PARNATE on one side and SB on the other side containing tranylcypromine sulfate equivalent to 10 mg of tranylcypromine.. Bottles of 100 tablets: NDC 0591-5590-01.

INDICATIONS & USAGE SECTION.


1 INDICATIONS USAGE. Tranylcypromine sulfate tablets are indicated for the treatment of major depressive disorder (MDD) in adult patients who have not responded adequately to other antidepressants. Tranylcypromine sulfate tablets are not indicated for the initial treatment of MDD due to the potential for serious adverse reactions and drug interactions, and the need for dietary restrictions[see Contraindications (4),Warnings and Precautions (5), and Drug Interactions (7)]. Tranylcypromine sulfate tablets are monoamine oxidase inhibitor (MAOI) indicated for the treatment of major depressive disorder (MDD) in adult patients who have not responded adequately to other antidepressants (1) Tranylcypromine sulfate tablets are not indicated for the initial treatment of MDD due to the potential for serious adverse reactions and drug interactions, and the need for dietary restrictions (1,4, 5, 7) Tranylcypromine sulfate tablets are monoamine oxidase inhibitor (MAOI) indicated for the treatment of major depressive disorder (MDD) in adult patients who have not responded adequately to other antidepressants (1) Tranylcypromine sulfate tablets are not indicated for the initial treatment of MDD due to the potential for serious adverse reactions and drug interactions, and the need for dietary restrictions (1,4, 5, 7).

INFORMATION FOR PATIENTS SECTION.


17 PATIENT COUNSELING INFORMATION. Advise the patient to read FDA-approved patient labeling (Medication Guide). Suicidal Thoughts and Behaviors Advise patients and caregivers to look for the emergence of suicidal thoughts and behaviors, especially early during treatment and when the dosage is adjusted up or down [see Box Warningand Warnings and Precautions (5.1)]. Hypertensive Crisis Advise the patient on possible symptoms and instruct the patient to seek immediate medical attention if related signs or symptoms are present [see Boxed Warningand Warnings and Precautions (5.2)] Serotonin Syndrome Advise the patient on possible symptoms, and explain the potentially fatal nature of serotonin syndrome and that it may result from an interaction with other serotonergic drugs. Instruct the patient to seek immediate medical attention if related signs or symptoms are present [see Warnings and Precautions (5.3)] Interaction with Other Drugs and Dietary Supplements [see Contraindications (4.1)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 health care provider able to provide advice on the potential for interactions.Explain to the patient that some other drugs may require medication-free interval even after discontinuation of tranylcypromine sulfate tablets.Advise the patient to inform other physicians, pharmacists, and dentists about the treatment with tranylcypromine sulfate 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 sulfate tablet treatment abruptly, as withdrawal symptoms may occur and that the effect of tranylcypromine sulfate 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 sulfate 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 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.Made in Italy Distributed by: Actavis Pharma, Inc. Parsippany, NJ 07054 USA Warn the patient not to take concomitant medications, whether prescription or over the counter drugs, or dietary supplements without prior consultation with health care provider able to provide advice on the potential for interactions.. Explain to the patient that some other drugs may require medication-free interval even after discontinuation of tranylcypromine sulfate tablets.. Advise the patient to inform other physicians, pharmacists, and dentists about the treatment with tranylcypromine sulfate tablets.. 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.. Warn the patient about the possible adverse reactions that can impair the performance of potentially hazardous tasks such as driving 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.

MECHANISM OF ACTION SECTION.


12.1 Mechanism of Action. The mechanism of action of tranylcypromine sulfate tablets as an antidepressant is not fully understood, but is presumed to be linked to potentiation of monoamine neurotransmitter activity in the central nervous system (CNS) resulting from its irreversible inhibition of the enzyme monoamine oxidase (MAO).

NONCLINICAL TOXICOLOGY SECTION.


13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis Mutagenesis Impairment Of Fertility. No carcinogenesis, mutagenesis, or fertility impairment studies were conducted.

OVERDOSAGE SECTION.


10 OVERDOSAGE. 10.1 Overdosage Symptoms, Signs and Laboratory Abnormalities. Overdose of tranylcypromine sulfate tablets can cause the adverse reactions generally associated with tranylcypromine sulfate tablets administration [see Warnings and Precautions (5), Adverse Reactions (6)and Drug Interactions (7.1)]. However, these reactions may be more severe, including fatal reactions. Effects reported with overdosage of tranylcypromine sulfate tablets and/or other MAOIs include: Insomnia, restlessness, and anxiety, progressing in severe cases to agitation, mental confusion, and incoherence; delirium; seizuresHypotension, dizziness, weakness, and drowsiness, progressing in severe cases to extreme dizziness and shockHypertension with severe headache and other symptoms/complicationsTwitching or myoclonic fibrillation of skeletal muscles, with hyperpyrexia, sometimes progressing to generalized rigidity and coma Insomnia, restlessness, and anxiety, progressing in severe cases to agitation, mental confusion, and incoherence; delirium; seizures. Hypotension, dizziness, weakness, and drowsiness, progressing in severe cases to extreme dizziness and shock. Hypertension with severe headache and other symptoms/complications. Twitching or myoclonic fibrillation of skeletal muscles, with hyperpyrexia, sometimes progressing to generalized rigidity and coma 10.2 Overdosage Management. There are no specific antidotes for tranylcypromine sulfate tablets. For current information on the management of poisoning or overdosage, contact poison control center at 1-800-222-1222. Abrupt withdrawal of tranylcypromine sulfate tablets following overdosage can precipitate withdrawal symptoms, including delirium [see Warnings and Precautions (5.9) and Drug Abuse and Dependence (9.3)]. Medical management should normally consist of general supportive measures, close observation of vital signs, and steps to counteract specific manifestations as they occur[see Warnings and Precautions (5)]. The toxic effects of tranylcypromine sulfate tablets may be delayed or prolonged following the last dose of the drug [see Clinical Pharmacology (12.2)]. Therefore, the patient should be closely observed for at least week. Data on the dialyzability of tranylcypromine are lacking.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.


PACKAGE LABEL.PRINCIPAL DISPLAY PANEL. Bottle LabelNDC 0591-5590-01 Tranylcypromine Sulfate Tablets 10 mg parnate bottle label.

PEDIATRIC USE SECTION.


8.4 Pediatric Use. Safety and effectiveness of tranylcypromine sulfate tablets in the pediatric population have not been established. All risks associated with the use of tranylcypromine sulfate tablets, including the risk of suicidal thoughts and behavior, apply to adults and pediatric patients[see Boxed Warningand Warnings and Precautions (5)].

PHARMACODYNAMICS SECTION.


12.2 Pharmacodynamics. Although tranylcypromine is eliminated in 24 hours, recovery MAO activity takes up to to days [see Warnings and Precautions (5.9)].

PREGNANCY SECTION.


8.1 Pregnancy. Risk Summary There are limited published reports of placental infarction and congenital anomalies in association with use of tranylcypromine sulfate tablets during pregnancy; however, these reports may not adequately inform the presence or absence of drug-associated risk with the use of tranylcypromine sulfate tablets during pregnancy. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Animal embryo-fetal development studies were not conducted with tranylcypromine; however, published animal reproduction studies report placental transfer of tranylcypromine in rats and dose-dependent decrease in uterine blood flow in pregnant sheep. Advise pregnant women of the potential risk to fetus.Clinical Considerations Labor or Delivery During labor and delivery, the potential for interactions between tranylcypromine sulfate tablets and drugs or procedures (e.g., epidural anesthesia) should be taken into account in women who have received tranylcypromine sulfate tablets[see Warnings and Precautions (5.6)and Drug Interactions (7.1)].

RECENT MAJOR CHANGES SECTION.


Boxed Warning 1/2018 Dosage and Administration (2) 1/2018 Contraindications (4) 1/2018 Warnings and Precautions (5) 1/2018.

SPL MEDGUIDE SECTION.


MEDICATION GUIDE. MEDICATION GUIDETRANYLCYPROMINE SULFATE (tran-ill-SIP-row-meen SULL-fate) TABLETS What is the most important information should know about tranylcypromine sulfate tablets Tranylcypromine sulfate tabletscan cause serious side effects including:Increase in suicidal thoughts or actions in some children, teenagers, and young adults within the first few months of treatment and when the tranylcypromine sulfate tablet dose is changed. Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions. Some people may have particularly high risk of having suicidal thoughts or actions.These include people who have, or have family history of, bipolar illness (also called manic-depressive illness) or suicidal thoughts or actions. Tranylcypromine sulfate tablets are not for use in children. How can watch for and try to prevent suicidal thoughts and actionsPay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is very important when an antidepressant medicine is started or when the dose is changed.Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings. Keep all follow-up visits with your healthcare provider as scheduled. Call the healthcare provider between visits as needed, especially if you have concerns about symptomsCall healthcare provider right away if you have any of the following symptoms, especially if they are new, worse, or worry you: thoughts about suicide or dyingattempts to commit suicide new or worse depressionnew or worse anxietyfeeling agitated, restless, angry or irritablepanic attackstrouble sleepingnew or worse irritabilityacting aggressive, being angry or violentacting on dangerous impulsesan extreme increase in activity or talking (mania)other unusual changes in behavior or moodA sudden, severe increase in blood pressure (hypertensive crisis). hypertensive crisis can happen when you eat certain foods and drinks certain beverages during or after tranylcypromine sulfate tablets treatment. hypertensive crisis can lead to stroke and death. People who have thyroid problems (hyperthyroidism) may have higher chance of having hypertensive crisis. Symptoms of hypertensive crisis may include:sudden, severe headachenauseavomitingstiff or sore necka fast heartbeat (palpitations) or change in the way your heart beatsexcessive sweating, sometimes with fever or cold, clammy skinthe pupils in your eyes increase in sizelight bothers your eyesfast or slow heart beat with chest painbleeding in your brainA hypertensive crisis can also happen if you take tranylcypromine sulfate tablets with certain other medicines. See, Who should not take tranylcypromine sulfate tablets Avoid foods and drinks with lot of tyramine while taking tranylcypromine sulfate tabletsand for weeks after you stop taking it. For list of some of the foods and drinks you should avoid during treatment with tranylcypromine sulfate tablets see, What should avoid while taking tranylcypromine sulfate tablets. Increase in suicidal thoughts or actions in some children, teenagers, and young adults within the first few months of treatment and when the tranylcypromine sulfate tablet dose is changed. Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions. Some people may have particularly high risk of having suicidal thoughts or actions.These include people who have, or have family history of, bipolar illness (also called manic-depressive illness) or suicidal thoughts or actions. Tranylcypromine sulfate tablets are not for use in children. Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is very important when an antidepressant medicine is started or when the dose is changed.. Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings. Keep all follow-up visits with your healthcare provider as scheduled. Call the healthcare provider between visits as needed, especially if you have concerns about symptoms. thoughts about suicide or dying. attempts to commit suicide new or worse depression. new or worse anxiety. feeling agitated, restless, angry or irritable. panic attacks. trouble sleeping. new or worse irritability. acting aggressive, being angry or violent. acting on dangerous impulses. an extreme increase in activity or talking (mania). other unusual changes in behavior or mood. sudden, severe increase in blood pressure (hypertensive crisis). hypertensive crisis can happen when you eat certain foods and drinks certain beverages during or after tranylcypromine sulfate tablets treatment. hypertensive crisis can lead to stroke and death. People who have thyroid problems (hyperthyroidism) may have higher chance of having hypertensive crisis. Symptoms of hypertensive crisis may include:. sudden, severe headache. nausea. vomiting. stiff or sore neck. fast heartbeat (palpitations) or change in the way your heart beats. excessive sweating, sometimes with fever or cold, clammy skin. the pupils in your eyes increase in size. light bothers your eyes. fast or slow heart beat with chest pain. bleeding in your brain. What are tranylcypromine sulfate tablets Tranylcypromine sulfate tablets are prescription medicine used to treat adults with certain type of depression called major depressive disorder (MDD) who have not responded well to treatment with other medicines used to treat depression (antidepressants). Tranylcypromine sulfate tablets belong to class of medicines called monoamine oxidase inhibitors (MAOIs) It is important to talk with your healthcare provider about the risks of treating depression and the risk of not treating it. Talk with your healthcare provider about all your treatment choices.Tranylcypromine sulfate tablets are not for use as the first medicine to treat MDD.It is not known if tranylcypromine sulfate tablets are safe and effective for use in children.. It is important to talk with your healthcare provider about the risks of treating depression and the risk of not treating it. Talk with your healthcare provider about all your treatment choices.. Tranylcypromine sulfate tablets are not for use as the first medicine to treat MDD.. It is not known if tranylcypromine sulfate tablets are safe and effective for use in children.. Who should not take tranylcypromine sulfate tablets Taking tranylcypromine sulfate tablets with certain antidepressants and certain pain, allergy symptom, and cold and cough symptom medicines may cause potentially life-threatening hypertensive crisis or problem called serotonin syndrome. See, What is the most important information should know about tranylcypromine sulfate tablets and What are the possible side effects of tranylcypromine sulfate tablets. Do not take tranylcypromine sulfate tablets if you:take certain medicines, including: antidepressants, such as: other monoamine oxidase inhibitors (MAOIs)selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs)tricyclic antidepressantsother antidepressants, such as amoxapine, bupropion, maprotiline, nefazodone, trazodone, vilazodone, vortioxetineamphetamines and methylphenidates medicines that can raise blood pressure (sympathomimetic medicine), such as pseudoephedrine, phenylephrine and ephedrine. These medicines are in some cold, hay fever or weight-loss medicines.sympathomimetic herbal medicines or dietary supplementsantihistamines (allergy medicines)triptansbuspironecarbamazepinedextromethorphandopaminehydroxytryptophan and tryptophanlevodopa and methyldopameperidinerasaglineresperines-adenosyl-L-methionine (SAM-e)tapentadoltetrabenazinAsk your healthcare provider or pharmacist if you are not sure if you take any of these medicines.have tumor on your adrenal gland called pheochromocytoma or type of tumor called paraganglioma.. take certain medicines, including: antidepressants, such as: other monoamine oxidase inhibitors (MAOIs)selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs)tricyclic antidepressantsother antidepressants, such as amoxapine, bupropion, maprotiline, nefazodone, trazodone, vilazodone, vortioxetineamphetamines and methylphenidates medicines that can raise blood pressure (sympathomimetic medicine), such as pseudoephedrine, phenylephrine and ephedrine. These medicines are in some cold, hay fever or weight-loss medicines.sympathomimetic herbal medicines or dietary supplementsantihistamines (allergy medicines)triptansbuspironecarbamazepinedextromethorphandopaminehydroxytryptophan and tryptophanlevodopa and methyldopameperidinerasaglineresperines-adenosyl-L-methionine (SAM-e)tapentadoltetrabenazin. antidepressants, such as: other monoamine oxidase inhibitors (MAOIs)selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs)tricyclic antidepressantsother antidepressants, such as amoxapine, bupropion, maprotiline, nefazodone, trazodone, vilazodone, vortioxetineamphetamines and methylphenidates other monoamine oxidase inhibitors (MAOIs). selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs). tricyclic antidepressants. other antidepressants, such as amoxapine, bupropion, maprotiline, nefazodone, trazodone, vilazodone, vortioxetine. amphetamines and methylphenidates. medicines that can raise blood pressure (sympathomimetic medicine), such as pseudoephedrine, phenylephrine and ephedrine. These medicines are in some cold, hay fever or weight-loss medicines.. sympathomimetic herbal medicines or dietary supplements. antihistamines (allergy medicines). triptans. buspirone. carbamazepine. dextromethorphan. dopamine. hydroxytryptophan and tryptophan. levodopa and methyldopa. meperidine. rasagline. resperine. s-adenosyl-L-methionine (SAM-e). tapentadol. tetrabenazin. have tumor on your adrenal gland called pheochromocytoma or type of tumor called paraganglioma.. Before taking tranylcypromine sulfate tablets, tell your healthcare provider about all your medical conditions, including if you:have high or low blood pressurehave heart problemshave cerebrovascular problems or have had strokehave headacheshave, or have family history of, bipolar disorder, mania, or hypomania plan to have surgeryhave liver or thyroid problems have or have had seizures or convulsionshave diabetesare pregnant or plan to become pregnant. Tranylcypromine sulfate tablets may harm your unborn baby.are breastfeeding or plan to breastfeed. Tranylcypromine sulfate passes into your breast milk. Do not breastfeed during treatment tranylcypromine sulfate tablets. Talk to your healthcare provider about the best way to feed your baby while taking tranylcypromine sulfate tablets.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Tranylcypromine sulfate tabletsand some other medicines may affect each other causing serious side effects. Tranylcypromine sulfate tabletsmay affect the way other medicines work, and other medicines may affect how tranylcypromine sulfate tablets work. Some medicines need to be stopped for period of time before you can start taking tranylcypromine sulfate tablets and for period of time after you stop taking tranylcypromine sulfate tablets Know the medicines you take. Keep list of them to show your healthcare providers, pharmacist, and dentist when you get new medicine.. have high or low blood pressure. have heart problems. have cerebrovascular problems or have had stroke. have headaches. have, or have family history of, bipolar disorder, mania, or hypomania plan to have surgery. have liver or thyroid problems have or have had seizures or convulsions. have diabetes. are pregnant or plan to become pregnant. Tranylcypromine sulfate tablets may harm your unborn baby.. are breastfeeding or plan to breastfeed. Tranylcypromine sulfate passes into your breast milk. Do not breastfeed during treatment tranylcypromine sulfate tablets. Talk to your healthcare provider about the best way to feed your baby while taking tranylcypromine sulfate tablets.. How should take tranylcypromine sulfate tabletsTake tranylcypromine sulfate tablets exactly as your healthcare provider tells you to take it.Your healthcare provider may need to change your dose of tranylcypromine sulfate tablets until it is the right dose for you.Do not stop taking tranylcypromine sulfate tablets without first talking to your healthcare provider. Stopping tranylcypromine sulfate tablets suddenly may cause withdrawal symptoms. See, What are the possible side effects of tranylcypromine sulfate tabletsTell your healthcare provider if you think your condition has gotten worse during treatment with tranylcypromine sulfate tablets. If you take too many tranylcypromine sulfate tablets (overdose) call your healthcare provider or poison control, or go to the nearest hospital emergency room right away. Take tranylcypromine sulfate tablets exactly as your healthcare provider tells you to take it.. Your healthcare provider may need to change your dose of tranylcypromine sulfate tablets until it is the right dose for you.. Do not stop taking tranylcypromine sulfate tablets without first talking to your healthcare provider. Stopping tranylcypromine sulfate tablets suddenly may cause withdrawal symptoms. See, What are the possible side effects of tranylcypromine sulfate tablets. Tell your healthcare provider if you think your condition has gotten worse during treatment with tranylcypromine sulfate tablets. If you take too many tranylcypromine sulfate tablets (overdose) call your healthcare provider or poison control, or go to the nearest hospital emergency room right away. What should avoid while taking tranylcypromine sulfate tabletsDo not eat foods or have drinks that have high amounts of tyramine while taking tranylcypromine sulfate tabletsor for weeks after you stop taking tranylcypromine sulfate tablets. All foods you eat should be fresh or properly frozen.Avoid foods when you do not know how those foods should be stored.Ask your healthcare provider if you are not sure if certain foods and drinks contain tyramine. The table below lists some of the foods and drinks you should avoid while you take tranylcypromine sulfate tablets.Type of Food and Drink that contain TyramineMeat, Poultry, and Fishair dried, aged and fermented meats, sausages, and salamispickled herringany spoiled or improperly stored meat, poultry, and fish. These foods have change in color, odor, or are moldy.spoiled or improperly stored animal liversVegetablesbroad bean pods (fava bean pods)Dairy (milk products)aged cheesesDrinksall tap beers and other beers that have not been pasteurized Otherconcentrated yeast extract (such as Marmite)most soybean products (including soy sauce and tofu)sauerkrautover-the-counter supplements containing tyramine Do not drive, operate heavy machinery, or do other dangerous activities until you know how tranylcypromine sulfate tablets affects you.Do not drink alcohol while taking tranylcypromine sulfate tablets.. Do not eat foods or have drinks that have high amounts of tyramine while taking tranylcypromine sulfate tabletsor for weeks after you stop taking tranylcypromine sulfate tablets. All foods you eat should be fresh or properly frozen.Avoid foods when you do not know how those foods should be stored.Ask your healthcare provider if you are not sure if certain foods and drinks contain tyramine. All foods you eat should be fresh or properly frozen.. Avoid foods when you do not know how those foods should be stored.. Ask your healthcare provider if you are not sure if certain foods and drinks contain tyramine.. air dried, aged and fermented meats, sausages, and salamis. pickled herring. any spoiled or improperly stored meat, poultry, and fish. These foods have change in color, odor, or are moldy.. spoiled or improperly stored animal livers. broad bean pods (fava bean pods). aged cheeses. all tap beers and other beers that have not been pasteurized concentrated yeast extract (such as Marmite). most soybean products (including soy sauce and tofu). sauerkraut. over-the-counter supplements containing tyramine Do not drive, operate heavy machinery, or do other dangerous activities until you know how tranylcypromine sulfate tablets affects you.. Do not drink alcohol while taking tranylcypromine sulfate tablets.. What are the possible side effects of tranylcypromine sulfate tablets Tranylcypromine sulfate tablets may cause serious side effects, including:See What is the most important information should know about tranylcypromine sulfate tabletsSerotonin Syndrome. potentially life-threatening problem called serotonin syndrome can happen when you take tranylcypromine sulfate tabletswith certain other medicines. See, Who should not take tranylcypromine sulfate tablets Symptoms of serotonin syndrome may include: agitation, confusionseeing or hearing things that are not real (hallucinations)comarapid pulsechanges in blood pressuredizzinesssweatingflushinghigh body temperature (hyperthermia)feverseizurestremors, stiff muscles, or muscle twitchingbecoming unstablenausea, vomiting, diarrhea If you have any of these symptoms, call your healthcare provider or go to the nearest hospital emergency room right away.Mania or hypomania (manic episodes) in people who have history of bipolar disorder. greatly increased energysevere problems sleepingracing thoughtsreckless behaviorunusually grand ideasexcessive happiness or irritabilitytalking more or faster than usual Low blood pressure (hypotension) including drop in your blood pressure when you stand or sit up (postural hypotension). This can happen more often in people who have high blood pressure (hypertension) and when the tranylcypromine sulfate tablet dose is changed. Postural hypotension may cause you to feel dizzy and faint (syncope).Changes in your blood pressure (hypotension or hypertension) during surgery and during the time around surgery (perioperative). Taking tranylcypromine sulfate tablets with certain medicines used for anesthesia can cause hypotension or hypertension. If you plan to have surgery, tell your surgeon or the healthcare provider who will give you anesthesia that you take tranylcypromine sulfate tablet Your healthcare provider should stop tranylcypromine sulfate tablets at least 10 days before you have surgery.Withdrawal symptoms. Talk with your healthcare provider before you stop taking tranylcypromine sulfate tablets Symptoms of withdrawal may include dizzinessnauseaheadache irritability and agitationproblems sleepingdiarrheaanxietyabnormal dreamssweatingconfusionelectric shock sensation (paresthesia)tirednesschanges in your moodhypomaniaringing in your ears (tinnitus)seizuresLiver problemsSeizures (convulsions). Seizures have happened in people who take too much tranylcypromine sulfate tablets .Low blood sugar (hypoglycemia). Hypoglycemia has happened in people with diabetes who take medicines to lower blood sugar. Talk with your healthcare provider about checking your blood sugar during treatment with tranylcypromine sulfate tablets Tell your healthcare provider if your blood sugar gets low.Worsening of symptoms that can happen with depression, such as anxiety and agitation.dry mouthdizzinessproblems sleepingfeeling sleepyheadacheoverexctextentconstipationblurry visionshakiness (tremor) These are not all the side effects of tranylcypromine sulfate tablets Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.. See What is the most important information should know about tranylcypromine sulfate tablets. Serotonin Syndrome. potentially life-threatening problem called serotonin syndrome can happen when you take tranylcypromine sulfate tabletswith certain other medicines. See, Who should not take tranylcypromine sulfate tablets Symptoms of serotonin syndrome may include: agitation, confusionseeing or hearing things that are not real (hallucinations)comarapid pulsechanges in blood pressuredizzinesssweatingflushinghigh body temperature (hyperthermia)feverseizurestremors, stiff muscles, or muscle twitchingbecoming unstablenausea, vomiting, diarrhea If you have any of these symptoms, call your healthcare provider or go to the nearest hospital emergency room right away.. agitation, confusion. seeing or hearing things that are not real (hallucinations). coma. rapid pulse. changes in blood pressure. dizziness. sweating. flushing. high body temperature (hyperthermia). fever. seizures. tremors, stiff muscles, or muscle twitching. becoming unstable. nausea, vomiting, diarrhea. Mania or hypomania (manic episodes) in people who have history of bipolar disorder. greatly increased energysevere problems sleepingracing thoughtsreckless behaviorunusually grand ideasexcessive happiness or irritabilitytalking more or faster than usual greatly increased energy. severe problems sleeping. racing thoughts. reckless behavior. unusually grand ideas. excessive happiness or irritability. talking more or faster than usual. Low blood pressure (hypotension) including drop in your blood pressure when you stand or sit up (postural hypotension). This can happen more often in people who have high blood pressure (hypertension) and when the tranylcypromine sulfate tablet dose is changed. Postural hypotension may cause you to feel dizzy and faint (syncope).. Changes in your blood pressure (hypotension or hypertension) during surgery and during the time around surgery (perioperative). Taking tranylcypromine sulfate tablets with certain medicines used for anesthesia can cause hypotension or hypertension. If you plan to have surgery, tell your surgeon or the healthcare provider who will give you anesthesia that you take tranylcypromine sulfate tablet Your healthcare provider should stop tranylcypromine sulfate tablets at least 10 days before you have surgery.. dizziness. nausea. headache irritability and agitation. problems sleeping. diarrhea. anxiety. abnormal dreams. sweating. confusion. electric shock sensation (paresthesia). tiredness. changes in your mood. hypomania. ringing in your ears (tinnitus). seizures. Liver problems. Seizures (convulsions). Seizures have happened in people who take too much tranylcypromine sulfate tablets .. Low blood sugar (hypoglycemia). Hypoglycemia has happened in people with diabetes who take medicines to lower blood sugar. Talk with your healthcare provider about checking your blood sugar during treatment with tranylcypromine sulfate tablets Tell your healthcare provider if your blood sugar gets low.. Worsening of symptoms that can happen with depression, such as anxiety and agitation.. dry mouth. dizziness. problems sleeping. feeling sleepy. headache. overexctextent. constipation. blurry vision. shakiness (tremor). How do store tranylcypromine sulfate tabletsStore tranylcypromine sulfate tablets between 59F to 86F (15C to 30C). Store tranylcypromine sulfate tablets in tight, light resistant container.Keep tranylcypromine sulfate tablets and all medicines out of the reach of children.. Store tranylcypromine sulfate tablets between 59F to 86F (15C to 30C). Store tranylcypromine sulfate tablets in tight, light resistant container.. General information about the safe and effective use of tranylcypromine sulfate tablets. Medicines are sometimes prescribed for purposes other than those listed in Medication Guide. Do not take tranylcypromine sulfate tablets for condition for which they were not prescribed. Do not give tranylcypromine sulfate tablets to other people, even if they have the same symptoms you have. It may harm them. You can ask your healthcare provider or pharmacist for information about tranylcypromine sulfate tablets that is written for health professionals.. What are the ingredients in tranylcypromine sulfate tablets Active Ingredient: tranylcypromine sulfate Inactive Ingredients: microcrystalline cellulose, anhydrous citric acid, croscarmellose sodium, D&C Red No. 7, FD&C Blue No. 2, FD&C Yellow No. 6, gelatin, lactose, magnesium stearate, talc, titanium dioxide, carnauba wax, polyethylene glycol 400 and 8000 and hypromelloseMade in Italy Distributed by: Actavis Pharma, Inc. Parsippany, NJ 07054 USA For more information, contact Actavis at 1-800-432-8534.. This Medication Guide has been approved by the U.S. Food and Drug Administration Issued:1/2018.

SPL UNCLASSIFIED SECTION.


2.1 Recommended Dosage. Tranylcypromine sulfate tablets are for oral use. The recommended dosage is 30 mg per day (in divided doses). If patients do not have an adequate response, increase the dosage in increments of 10 mg per day every to weeks to maximum 30 mg twice daily (60 mg per day). Dosage increases should be made more gradually in patients at risk for hypotension (e.g., geriatric patients) [see Warnings and Precautions (5.5)].

USE IN SPECIFIC POPULATIONS SECTION.


8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Risk Summary There are limited published reports of placental infarction and congenital anomalies in association with use of tranylcypromine sulfate tablets during pregnancy; however, these reports may not adequately inform the presence or absence of drug-associated risk with the use of tranylcypromine sulfate tablets during pregnancy. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Animal embryo-fetal development studies were not conducted with tranylcypromine; however, published animal reproduction studies report placental transfer of tranylcypromine in rats and dose-dependent decrease in uterine blood flow in pregnant sheep. Advise pregnant women of the potential risk to fetus.Clinical Considerations Labor or Delivery During labor and delivery, the potential for interactions between tranylcypromine sulfate tablets and drugs or procedures (e.g., epidural anesthesia) should be taken into account in women who have received tranylcypromine sulfate 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 breastfed child; however, because of the potential for serious adverse reactions in breastfed infant, advise nursing women to discontinue breastfeeding during treatment with tranylcypromine sulfate tablets.. 8.4 Pediatric Use. Safety and effectiveness of tranylcypromine sulfate tablets in the pediatric population have not been established. All risks associated with the use of tranylcypromine sulfate tablets, including the risk of suicidal thoughts and behavior, apply to adults and pediatric patients[see Boxed Warningand 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.