Data from FDA (Food and Drug Administration, USA) - Curated by EPG Health - Last updated 09 February 2018

Indication(s)

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 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 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)

Learning Zones

An epgonline.org Learning Zone (LZ) is an area of the site dedicated to providing detailed self-directed medical education about a disease, condition or procedure.

Idiopathic Pulmonary Fibrosis

Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic interstitial lung disease that occurs mostly in older adults, is limited to the lungs and often displays a characteristic imaging and histological appearance. Find out how to diagnose IPF and the latest interventions available for patients living with this burden.

Chronic Lymphocytic Leukaemia (CLL)

Chronic Lymphocytic Leukaemia (CLL)

Refine your knowledge of chronic lymphocytic leukaemia (CLL) with information on pathophysiology, diagnosis, treatment options and more

+ 1 more

Transplantation

Transplantation

See information on best practice in solid organ transplantation, and expert discussions on related hot topics.

Load more

Related Content

Advisory information

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 sulfate 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 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 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 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)].
Adverse reactions
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 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/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) 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 Actavis at 1-800-432-8534 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Usage information

Dosing and administration
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 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 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 Sulfate 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 sulfate 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 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 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 sulfate tablets therapy. Higher daily doses and longer duration of use appear to be associated with a 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 a history of mania [see Warnings and Precautions(5.4)]. Measure blood pressure [see Warnings and Precautions (5.2, 5.5)].
Use in special populations
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 a dose-dependent decrease in uterine blood flow in pregnant sheep. Advise pregnant women of the potential risk to a 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 a breastfed child; however, because of the potential for serious adverse reactions in a breastfed infant, advise nursing women to discontinue breastfeeding during treatment with tranylcypromine 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.

Interactions

7 DRUG INTERACTIONS See Full Prescribing Information for a list of products, foods and beverages that can interact with tranylcypromine sulfate 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 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 a healthcare provider able to provide advice on the potential for interactions. Time to Start Tranylcypromine Sulfate Tablets after Discontinuation of a Contraindicated Drug For products that are contraindicated with tranylcypromine sulfate 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 sulfate 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 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., 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 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 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 sulfate 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* Product Clinical Comment on Concomitant Usea Predominant Effect/Risk [Hypertensive Reaction (HR)b or Serotonin Syndrome (SS)c] Agents with blood pressure-reducing effects Use with cautiond Hypotensione Non-selective H1 receptor antagonists Contraindicateda Increased anticholinergic effects Beta-adrenergic blockers (see also agents or procedures with blood pressure-reducing effects) Use with the cautiond More pronounced bradycardia, postural hypotensione Blood glucose-lowering agents Dosage reduction of such agents may be necessary. Monitor blood glucose. Excessive reduction of blood glucose (additive effect)f CNS depressant agents (including opioids, alcohol, sedatives, hypnotics) Use with cautiond Increased CNS depression Dietary supplements containing sympathomimetics Contraindicateda Antidepressants including but not limited to: Other MAOIs (e.g., linezolid, intravenous methylene blue, selective MAOIs) Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) Tricyclic antidepressants Amoxapine, bupropion, maprotiline, nefazodone, trazodone, vilazodone, vortioxetine Contraindicateda SS for all antidepressants For MAOIs, increased MAO inhibition and risk of adverse reactions, SS, and HRg Amphetamines and methylphenidates and derivatives Contraindicateda HR Sympathomimetic drugs** Contraindicateda HR; Including risk of intracerebral hemorrhage Triptans Contraindicateda SS * Some drugs in these groups may also be listed in Table 4 below. ** Sympathomimetic drugs include amphetamines as well as cold, hay fever or weight-reducing products that contain vasoconstrictors such as pseudoephedrine, phenylephrine, and ephedrine) a [See Contraindications (4.1)] ; b [See Warnings and Precautions (5.2)] ; c [ See Warnings and Precautions (5.3)] d If not otherwise specified in this table, consider avoiding concomitant use (see also information on medication-free intervals, use agent at the lowest appropriate dosage, monitor for effects of the interaction, advise the patient to report potential effects). e [See Warnings and Precautions (5.5)] ; f [See Warnings and Precautions (5.14)] ; g [See Overdosage (10.1)] Table 4: Clinically Significant Drug Interactions with Individual Products* Product Clinical Comment on Concomitant Usea Predominant Effect/Risk [Hypertensive Reaction (HR)b or Serotonin Syndrome (SS)c] Altretamine Use with cautiond Orthostatic hypotensione Buspirone Contraindicateda HR Carbamazepine Contraindicateda SS Chlorpromazine Use with cautiond Hypotensive effectse Cyclobenzaprine Contraindicateda SS Dextromethorphan Contraindicateda SS; Psychosis, bizarre behavior Dopamine Contraindicateda HR Droperidol Use with cautiond QT interval prolongation Entacapone Use with cautiond HR Fentanyl Use with cautiond SS Hydroxytryptophan Contraindicateda SS Levodopa Contraindicateda HR Lithium Use with cautiond SS Meperidine Contraindicateda SS Methadone Use with cautiond SS Methyldopa Contraindicateda HR Metoclopramide Use with cautiond HR/SS Mirtazapine Contraindicateda SS Oxcarbazepine Use with cautiond because of close structural relationship with tricyclic antidepressants SS Rasagiline Contraindicateda HR Reserpine Contraindicateda HR S-adenosyl-L-methionine (SAM-e) Contraindicateda SS Tapentadol Contraindicateda HR/SS Tetrabenazine Contraindicateda HR Tolcapone Use with cautiond HR Tramadol Use with cautiond SS; Increased seizure risk Tryptophan Contraindicateda SS *Some drugs in this table may also belong to groups listed in Table 3 above, and may be associated with additional interactions. a [ 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)] 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 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 sulfate tablets-treated patients to avoid foods and beverages with significant tyramine content during treatment with tranylcypromine sulfate 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 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 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

More information

Category Value
Authorisation number NDA012342
Agency product number 7ZAT6ES870
Orphan designation No
Product NDC 0591-5590
Date Last Revised 29-01-2018
Type HUMAN PRESCRIPTION DRUG
Marketing authorisation holder Actavis Pharma, Inc.
Warnings 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 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 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)