Tranylcypromine

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 Use a Predominant Effect/Risk [Hypertensive Reaction (HR) b or Serotonin Syndrome (SS) c ] Agents with blood pressure-reducing effects Use with caution d Hypotension e Non-selective H1 receptor antagonists Contraindicated a Increased anticholinergic effects Beta-adrenergic blockers (see also agents or procedures with blood pressure-reducing effects) Use with the caution d More pronounced bradycardia, postural hypotension e 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 caution d Increased CNS depression Dietary supplements containing sympathomimetics Contraindicated a 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 a SS for all antidepressants For MAOIs, increased MAO inhibition and risk of adverse reactions, SS, and HR g Amphetamines and methylphenidates and derivatives Contraindicated a HR Sympathomimetic drugs** Contraindicated a HR; Including risk of intracerebral hemorrhage Triptans Contraindicated a 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 Use a Predominant Effect/Risk [Hypertensive Reaction (HR) b or Serotonin Syndrome (SS) c ] Altretamine Use with caution d Orthostatic hypotension e Buspirone Contraindicated a HR Carbamazepine Contraindicated a SS Chlorpromazine Use with caution d Hypotensive effects e Cyclobenzaprine Contraindicated a SS Dextromethorphan Contraindicated a SS; Psychosis, bizarre behavior Dopamine Contraindicated a HR Droperidol Use with caution d QT interval prolongation Entacapone Use with caution d HR Fentanyl Use with caution d SS Hydroxytryptophan Contraindicated a SS Levodopa Contraindicated a HR Lithium Use with caution d SS Meperidine Contraindicated a SS Methadone Use with caution d SS Methyldopa Contraindicated a HR Metoclopramide Use with caution d HR/SS Mirtazapine Contraindicated a SS Oxcarbazepine Use with caution d because of close structural relationship with tricyclic antidepressants SS Rasagiline Contraindicated a HR Reserpine Contraindicated a HR S-adenosyl-L-methionine (SAM-e) Contraindicated a SS Tapentadol Contraindicated a HR/SS Tetrabenazine Contraindicated a HR Tolcapone Use with caution d HR Tramadol Use with caution d SS; Increased seizure risk Tryptophan Contraindicated a 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)] d If not otherwise specified in this table, consider avoiding concomitant use (see also information on medication-free intervals , use agent at the lowest appropriate dose, monitor for effects of the interaction, advise the patient to report potential effects, and be prepared to discontinue the agent and treat effects of the interaction e [ 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,…

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)].