Indicated for the treatment of major depressive disorder (MDD) in adult patients who have not responded adequately to other antidepressants. PARNATE is 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.

Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. PARNATE is not approved for use in pediatric patients. 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 PARNATE, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.

Excessive consumption of foods or beverages with significant tyramine content or the use of certain drugs with PARNATE or after PARNATE discontinuation can precipitate hypertensive crisis. Monitor blood pressure and allow for medication-free intervals between administration of PARNATE and interacting drugs. Instruct patients to avoid ingestion of foods and beverages with high tyramine content. Instruct patients to avoid foods and beverages with high tyramine content while being treated with PARNATE and for 2 weeks after stopping PARNATE.

Patients with hyperthyroidism may be at greater risk of hypertensive crisis.

PARNATE is contraindicated in the presence of pheochromocytoma or other catecholamine-releasing paragangliomas because such tumors secrete pressor substances and can lead to hypertensive crisis.

Careful evaluation of the benefits and risks of PARNATE 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

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 non-psychiatric disorders (such as linezolid or intravenous methylene blue).

In patients with bipolar disorder, treating a depressive episode with PARNATE or another antidepressant may precipitate a mixed/manic episode. Prior to initiating treatment with PARNATE, screen patients for any personal or family history of bipolar disorder, mania, or hypomania.

Hypotension, including postural hypotension, has been observed during therapy with PARNATE. At doses above 30 mg daily, postural hypotension is a major adverse reaction and may result in syncope.

It is recommended that PARNATE 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 PARNATE. 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 PARNATE (e.g., hypertension associated with the use of vasoconstrictors in local anesthetics).

Abrupt discontinuation or dosage reduction of PARNATE 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.

Hepatitis and elevated aminotransferases have been reported in association with PARNATE administration. Patients should be monitored accordingly. PARNATE should be discontinued in patients who develop signs and symptoms of hepatotoxicity. Sedation has occurred in PARNATE-treated patients with cirrhosis. Patients with cirrhosis receiving PARNATE should be monitored for possible increased risks of central nervous system adverse reactions, such as excessive drowsiness.

Seizures have been reported with PARNATE withdrawal after abuse, and with overdose.

PARNATE may aggravate coexisting symptoms in depression, such as anxiety and agitation.

Some PARNATE adverse reactions (e.g., hypotension, faintness, drowsiness, confusion, disorientation) can impair a patient’s ability to operate machinery or use an automobile.

PARNATE 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. Instruct PARNATE-treated patients to avoid foods and beverages with significant tyramine content during treatment with PARNATE or within 2 weeks of stopping treatment.

Tyramine-Rich Foods and Beverages to Avoid:

• 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
• Broad bean pods (fava bean pods)
• Aged cheeses
• All varieties of tap beer and beers that have not been pasteurized so as to allow for ongoing fermentation and excessive amounts of caffeine
• Concentrated yeast extract (e.g., Marmite), sauerkraut, most soybean products (including soy sauce and tofu), OTC supplements containing tyramine, and chocolate

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 PARNATE to reduce the risk of additive effects.

After stopping PARNATE treatment, at least one week should elapse before starting another MAOI (intended to treat MDD) or other contraindicated antidepressants.

Concomitant use of PARNATE or use in rapid succession with the following products is contraindicated. Such use may cause severe or life-threatening reactions such as hypertensive crises or serotonin syndrome. Medication-free periods between administration of PARNATE and contraindicated agents are recommended:

• Non-selective H1 receptor antagonists
• Antidepressants including but not limited to: other monoamine oxidase inhibitors MAOIs ((e.g., linezolid, intravenous methylene blue, selective MAOIs), selective serotonin reuptake inhibitors (SSRIs), 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
• Buspirone, levodopa, mirtazapine, S-adenosyl-L-methionine (SAM-e), carbamazepine, meperidine, tapentadol, cyclobenzaprine, methyldopa, tetrabenazine, dextromethorphan, milnacipran, tryptophan, dopamine, rasagiline, hydroxytryptophan and reserpine
• Caution needed when used with the following drugs: agents with blood pressure-reducing effects, beta-adrenergic blockers, CNS depressant agents (including opioids, alcohol, sedatives, hypnotics), Altretamine, Chlorpromazine, Droperidol, Entacapone, Fentanyl, Lithium, Methadone, Metoclopramide, Oxcarbazepine, Tolcapone and Tramadol

There are limited published reports of placental infarction and congenital anomalies in association with use of PARNATE during pregnancy; however, these reports may not adequately inform the presence or absence of drug-associated risk with the use of PARNATE during pregnancy. Advise pregnant women of the potential risk to a fetus.

Tranylcypromine is present in human milk.

GoToSource

• Dosage greater than 60 mg per day. GoToSource

• Use in patients under the age of 18. GoToSource

• Initial treatment of MDD. GoToSource

• Social anxiety and panic disorder. GoToSource

• Narcolepsy. GoToSource

• Phobias, post traumatic stress disorder and migraine headaches resistant to other therapies. GoToSource

• Parkinson’s disease. GoToSource

• Refractory bipolar depression. GoToSource  

Orthostatic hypotension, weight gain, swelling, muscle pain, myoclonus (involuntary jerking of a muscle or group of muscles), paresthesias (abnormal sensation), sexual dysfunction, liver damage, hypertensive crisis, serotonin syndrome (life-threatening drug interaction) and worsening depression or suicidality. GoToSource

Withdrawal syndrome. GoToSource

Increased risk of seizures for patients with epilepsy. GoToSource

Abuse and dependence. GoToSource 

Neuroleptic malignant syndrome (life-threatening neurological disorder). GoToSource 

Acute cerebral hemorrhage. GoToSource 

Hypersomnolence (excessive daytime sleepiness or prolonged nighttime sleep) and fatigue. GoToSource 

Fatal disseminated intravascular coagulation (life-threatening condition that prevents blood from clotting normally) after use with clomipramine. GoToSource 

Lawsuits filed for serotonin syndrome and hypertensive crisis.