TRANYLCYPROMINE

Brand names: Tranylcypromine

Boxed warning

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS and HYPERTENSIVE CRISIS WITH SIGNIFICANT TYRAMINE USE WARNING: SUICIDAL THOUGHTS AND BEHAVIORS and HYPERTENSIVE CRISIS WITH SIGNIFICANT TYRAMINE USE See 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 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 ) 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 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 tablets or after tranylcypromine tablets discontinuation can precipitate hypertensive crisis. Monitor blood pressure and allow for medication-free intervals between administration of tranylcypromine 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) ] .

Warnings

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 tablets dosage or concomitant medication as necessary ( 5.5 ) • Hypotension and Hypertension during Anesthesia and Perioperative Care : If possible, discontinue tranylcypromine 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 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 Hypertensive 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. Hypertension 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, hyperreflexia, 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 are 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 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 tablets-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.

Contraindications

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 Drug 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) ] .

Overdose

10 OVERDOSAGE 10.1 Overdosage Symptoms, Signs, and Laboratory Abnormalities Overdose of tranylcypromine tablets can cause the adverse reactions generally associated with tranylcypromine 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 tablets and/or other MAOIs include: • 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 tablets. For current information on the management of poisoning or overdosage, contact a poison control center at 1-800-222-1222. Abrupt withdrawal of tranylcypromine 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 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 1 week. Data on the dialyzability of tranylcypromine are lacking.

Drug interactions

7 DRUG INTERACTIONS See Full Prescribing Information for a list of products, foods and beverages that can interact with tranylcypromine tablets ( 7 ) 7.1 Clinically-Significant Drug Interactions Tables 3 and 4 lists drug classes and individual products, respectively, with a potential for interaction with tranylcypromine 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 a healthcare provider able to provide advice on the potential for interactions. Time to Start Tranylcypromine Tablets after Discontinuation of a Contraindicated Drug For products that are contraindicated with tranylcypromine tablets, a time period of 4 to 5 half-lives of the other product 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 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. Time 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 Some drugs in these groups may also be listed in Table 4 below. Product Clinical Comment on Concomitant Use [See Contraindications (4.1)] ; Predominant Effect/Risk [Hypertensive Reaction (HR) [See Warnings and Precautions (5.2)] ; or Serotonin Syndrome (SS) [See Warnings and Precautions (5.3)] ] Agents with blood pressure-reducing effects Use with caution 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). Hypotension [See Warnings and Precautions (5.5)] ; Non-selective H1 receptor antagonists Contraindicated Increased anticholinergic effects Beta-adrenergic blockers (see also agents or procedures with blood pressure-reducing effects) Use with caution More pronounced bradycardia, postural hypotension Blood glucose-lowering agents Dosage reduction of such agents may be necessary. Monitor blood glucose. Excessive reduction of blood glucose (additive effect) [See Warnings and Precautions (5.14)] ; CNS depressant agents (including opioids, alcohol, sedatives, hypnotics) Use with caution Increased CNS depression Dietary supplements containing sympathomimetics Contraindicated 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 Contraindicated SS for all antidepressants For MAOIs, increased MAO inhibition and risk of adverse reactions, SS, and HR [See Overdosage (10.1)] Amphetamines and methylphenidates and derivatives Contraindicated HR Sympathomimetic drugs Sympathomimetic drugs include amphetamines as well as cold, hay fever or weight-reducing products that contain vasoconstrictors such as pseudoephedrine, phenylephrine, and ephedrine) Contraindicated HR; Including risk of intracerebral hemorrhage Triptans Contraindicated SS Table 4: Clinically Significant Drug Interactions with Individual Products Some drugs in this table may also belong to groups listed in Table 3 above, and may be associated with additional interactions. Product Clinical Comment on Concomitant Use [See Contraindications (4.1)] ; Predominant Effect/Risk [Hypertensive Reaction (HR) [See Warnings and Precautions (5.3)] ; or Serotonin Syndrome (SS) [See Warnings and Precautions (5.7)] ] Altretamine Use with caution 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 Orthostatic hypotension [See Warnings and Precautions (5.5)] Buspirone Contraindicated HR Carbamazepine Contraindicated SS Chlorpromazine Use with caution Hypotensive effects Cyclobenzaprine Contraindicated SS Dextromethorphan Contraindicated SS; Psychosis, bizarre behavior Dopamine Contraindicated HR Droperidol Use with caution QT interval prolongation Entacapone Use with caution HR Fentanyl Use with caution SS Hydroxytryptophan Contraindicated SS Levodopa Contraindicated HR Lithium Use with caution SS Meperidine Contraindicated SS Methadone Use with caution SS Methyldopa Contraindicated HR Metoclopramide Use with caution HR/SS Mirtazapine Contraindicated SS Oxcarbazepine Use with caution because of close structural relationship with tricyclic antidepressants SS Rasagiline Contraindicated HR Reserpine Contraindicated HR S-adenosyl-L-methionine (SAM-e) Contraindicated SS Tapentadol Contraindicated HR/SS Tetrabenazine Contraindicated HR Tolcapone Use with caution HR Tramadol Use with caution SS; Increased seizure risk Tryptophan Contraindicated SS 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 tablets-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 Class of Food or Beverage Tyramine-Rich Foods and Beverages to Avoid Acceptable Foods and Drinks, 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

Uses

1 INDICATIONS AND 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 )

Dosage forms & strengths

TABLET
TRANYLCYPROMINE SULFATE 10 mg/1

2 DOSAGE AND 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) ] .

All identified pills

Side effects

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: 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/overexcitement, manic symptoms/hypomania, agitation, insomnia, anxiety, confusion, disorientation, loss of libido Nervous system disorders: dizziness, restlessness/akathisia, akinesia, ataxia, myoclonic jerks, tremor, hyperreflexia, 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 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 Solco Healthcare US, LLC at 1-866-257-2597 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Official source

DailyMed