Tranylcypromine

1 INDICATIONS & USAGE Tranylcypromine tablets are indicated for the treatment of major depressive disorder (MDD) in adult patients who have not responded adequately to other antidepressants. Tranylcypromine 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 tablets are a 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 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)

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 1 to 3 weeks to a 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 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 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 1 to 3 weeks to a 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 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)].

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) 4.1 Combination with Certain Drugs Concomitant use of tranylcypromine tablets or use in rapid succession with the products in Table 1 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 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 Tablets Dr ug Classes Non-selective H1 receptor antagonists Antidepressants including but not limited to: 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) Amphetamines and methylphenidates and derivatives Sympathomimetic products (e.g., cold, hay fever or weight-reducing products that contain vasoconstrictors such as pseudoephedrine, phenylephrine, and ephedrine; or dietary supplements that contain sympathomimetics) Triptans Individual Drugs (not included in the above classes) buspirone levodopa s-adenosyl-L-methionine (SAM-e) carbamazepine meperidine tapentadol cyclobenzaprine methyldopa tetrabenazine dextromethorphan milnacipran tryptophan dopamine rasagiline hydroxytryptophan reserpine 4.2 Pheochromocytoma and Catecholamine-Releasing Paragangliomas Tranylcypromine 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)].

Not available.

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 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 .