tranylcypromine sulfate
Parnate

Available forms
Available by prescription only
Tablets: 10 mg

Indications and dosages
 Severe depression, panic disorder. Adults: 30 mg P.O. daily in divided doses. If there’s no improvement after 2 weeks, increase daily dose by 10 mg q 1 to 3 weeks. Maximum dose is 60 mg daily.

Pharmacodynamics
Antidepressant action: Endogenous depression is thought to result from low CNS levels of neurotransmitters, including norepinephrine and serotonin. Tranylcypromine inhibits effects of MAO, an enzyme that normally inactivates amine-containing substances, thus increasing their concentration and activity.

Pharmacokinetics
Absorption: Rapidly and completely absorbed from GI tract.
Distribution: Not fully understood. Dosage adjustments determined by therapeutic response and adverse reaction profile.
Metabolism: Metabolized in liver.
Excretion: Drug is excreted primarily in urine within 24 hours; some drug is excreted in feces via biliary tract. Half-life is 2 1/2 hours. Enzyme inhibition prolonged and unrelated to half-life.

Contraindications and precautions
Contraindicated in patients receiving MAO inhibitors, dibenzazepine derivatives, sympathomimetics (such as amphetamines), some CNS depressants (such as narcotics and alcohol), selective serotonin reuptake inhibitors, antihypertensives, diuretics, antihistamines, sedatives, anesthetics, bupropion hydrochloride, buspirone hydrochloride, dextromethorphan, or meperidine.
  Also contraindicated in patients consuming foods with a high tyramine or tryptophan content or excessive quantities of caffeine; in those with a confirmed or suspected cerebrovascular defect, pheochromocytoma, history of liver disease, severe impairment of renal function, CV disease, hypertension, or history of headache; and in those undergoing elective surgery.
 Use cautiously in patients with renal disease, diabetes, seizure disorders, Parkinson’s disease, or hyperthyroidism; in those at risk for suicide; and in patients receiving antiparkinsonians or spinal anesthetics.

Interactions
Drug-drug. Amphetamines, ephedrine, phenylephrine, other related drugs: May result in serious CV toxicity. Don’t use together.
Barbiturates, dextromethorphan, narcotics, other sedatives: Increases CNS depressant effects. Reduce dosage if use together can’t be avoided.
Cocaine, local anesthetics containing vasoconstrictors: May precipitate hypertension. Avoid use.
Disulfiram: May cause tachycardia, flushing, or palpitations. Don’t use together. If use together can’t be avoided, use cautiously.
General or spinal anesthetics normally metabolized by MAO inhibitors: Causes severe hypotension and excessive CNS depression. Stop tranylcypromine for at least 1 week before using these drugs.
Local anesthetics (such as lidocaine, procaine): Decreases therapeutic effect; causes poor nerve block. Don’t use together.
Meperidine: Causes circulatory collapse and death. Don’t use together.
Tricyclic antidepressants: Enhances adverse CNS effects. Wait at least 2 weeks before switching to these drugs.
Drug-herb. Ginseng: May cause adverse reactions, including headache, tremors, mania. Discourage use together.
Drug-food. Foods high in caffeine, tryptophan, tyramine: May cause hypertensive crisis. Discourage use together.
Drug-lifestyle. Alcohol use: Potentiates CNS effects. Discourage alcohol use.

Adverse reactions
CNS: dizziness, headache, anxiety, agitation, paresthesia, drowsiness, weakness, numbness, tremor, jitters, confusion.
CV: orthostatic hypotension, tachycardia, paradoxical hypertension, palpitations, edema.
EENT: blurred vision, tinnitus.
GI: dry mouth, anorexia, nausea, diarrhea, constipation, abdominal pain.
GU: impotence, urine retention, elevated urinary catecholamine levels, impaired ejaculation.
Hematologic: anemia, leukopenia, agranulocytosis, thrombocytopenia.
Hepatic: hepatitis.
Musculoskeletal: muscle spasm, myoclonic jerks.
Skin: rash.
Other: SIADH, chills.

Effects on lab test results
• May increase ALT and AST levels.
• May decrease hemoglobin and WBC, granulocyte, and platelet counts.

Overdose and treatment
Signs and symptoms of overdose include exacerbations of adverse reactions or an exaggerated response to normal pharmacologic activity; such signs and symptoms become apparent slowly (24 to 48 hours) and may persist for up to 2 weeks. Agitation, flushing, tachycardia, hypotension, hypertension, palpitations, increased motor activity, twitching, increased deep tendon reflexes, seizures, hyperpyrexia, cardiorespiratory arrest, or coma may occur. Death has occurred with doses of 350 mg.
 Treat symptomatically and supportively. Give 5 to 10 mg of phentolamine I.V. push for hypertensive crisis; treat seizures, agitation, or tremors with I.V. diazepam, tachycardia with beta blockers, and fever with cooling blankets. Monitor vital signs and fluid and electrolyte balance.

Special considerations
• Consider the inherent risk of suicide until significant improvement of depressive state occurs. Closely supervise high-risk patients during initial drug therapy. To reduce risk of suicidal overdose, prescribe smallest quantity of tablets consistent with good management.
• Tranylcypromine may have a more rapid onset of antidepressant effect compared with other MAO inhibitors (7 to 10 days versus 21 to 30 days). MAO activity also returns rapidly to pretreatment values.
• Monitor patient for adverse effects.
Breast-feeding patients
• Safety in breast-feeding women hasn’t been established.
Pediatric patients
• Drug isn’t recommended for children younger than age 16.
Geriatric patients
• Drug isn’t recommended for patients older than age 60 because they have less compensatory reserve to cope with serious adverse effects of drug.

Patient education
• Warn patient to avoid taking alcohol, other CNS depressants, and self-prescribed drugs, such as cold, hay fever, or diet preparations, without medical approval.
• To minimize daytime sedation, tell patient to take drug at bedtime.
• Explain that many foods and beverages containing tyramine or tryptophan (such as wines, beer, cheeses, preserved fruits, meats, and vegetables) may interact with drug. A list of foods to avoid can be obtained from the hospital dietary department or pharmacy.
• Tell patient to avoid hazardous activities that require alertness until full effect of drug on CNS is known.
• Inform patient to lie down after taking drug and to avoid abrupt postural changes, especially when arising, to prevent dizziness induced by orthostatic blood pressure changes.
• Caution patient to take drug exactly as prescribed, not to double a missed dose, and not to stop taking drug abruptly. Advise him to promptly report any adverse reactions and tell him that dosage reduction can relieve most adverse reactions.
• Tell patient to inform dentist or other health care providers about the use of an MAO inhibitor.
• Inform patient to report severe headache, palpitations, tachycardia, sweating, tightness in throat and chest, dizziness, stiff neck, nausea, vomiting, or other unusual symptoms.
• Advise patient to store drug safely away from children.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use