Tranylcypromine Dosage

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Usual Adult Dose for:

Additional dosage information:

Usual Adult Dose for Depression

Major Depressive Episode Without Melancholia:
Initial dose: 10 mg orally twice a day
Maintenance dose: Usually 30 mg/day in divided doses is effective; however, dosage should be adjusted to individual needs

Improvement should be seen within 48 hours to 3 weeks after initiation of therapy. If there are no signs of improvement after 2 weeks, then the dosage may be increased in 10 mg/day at intervals of 1 to 3 weeks, up to a maximum of 60 mg/day.

Renal Dose Adjustments

The manufacturer recommends caution when administering this drug to patients with impaired renal function.

Liver Dose Adjustments

The use of tranylcypromine is contraindicated in patients with a history of liver disease and in patients with abnormal liver function tests.

Dose Adjustments

If the patient is being transferred to tranylcypromine from another monoamine oxidase inhibitor or from a dibenzazepine-related entity (e.g., tricyclic antidepressants), a medication-free interval of at least a week should be allowed, then tranylcypromine should be initiated at half the normal starting dosage for at least the first week of therapy.

Precautions

Children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder and other psychiatric disorders may be at an increased risk of suicidal thinking and suicidality with antidepressant use. This risk should be balanced with clinical need when considering the use of tranylcypromine or any other antidepressant in a child, adolescent, or young adult. All patients who are treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior, particularly during the first few months of treatment, or when the dose either increases or decreases. Discontinuing or modifying the current drug therapy should be considered in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality (particularly if symptoms are severe, abrupt in onset, or were not part of the presenting symptoms). Prescriptions for tranylcypromine and other psychotropic drugs should be written for the smallest quantity feasible in order to reduce the risk of an attempt to overdose. Health care providers should instruct patients, their families, and their caregivers to be alert for the emergence of agitation, irritability, and other symptoms, as well as the emergence of suicidality and worsening depression, and to report such symptoms immediately to their health care provider.

Tranylcypromine is not approved for treating bipolar disorder. Patients should be adequately screened to determine if they are at risk for bipolar disorder prior to initiating therapy with tranylcypromine so that they can be appropriately monitored during treatment. Such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.

The use of tranylcypromine is contraindicated in patients with a history of liver disease and in patients with abnormal liver function tests. Tranylcypromine increases pressor amines and is contraindicated in patients with cardiovascular disease, hypertension, a history of severe or frequent headaches, or a confirmed or suspected cerebrovascular defect. Tranylcypromine is also contraindicated in patients with pheochromocytoma, since such tumors secrete pressor substances.

Tranylcypromine is contraindicated in combination with monoamine oxidase (MAO) inhibitors or with dibenzazepine-related entities. Tranylcypromine should not be administered together or in rapid succession with other MAO inhibitors or dibenzazepine-related entities (e.g., tricyclic antidepressants, cyclobenzaprine, carbamazepine) because coadministration may lead to hypertensive crises or severe convulsive seizures. At least 7 to 14 days should elapse between discontinuation of tranylcypromine therapy and initiation of treatment with these drugs, and vice versa.

Coadministration of an MAO inhibitor and bupropion is contraindicated. At least 14 days should elapse between discontinuation of an MAO inhibitor and initiation of treatment with bupropion.

Tranylcypromine is contraindicated in combination with selective serotonin reuptake inhibitors (SSRI) or selective norepinephrine reuptake inhibitors (SNRI). SSRIs and SNRIs should not be used within 14 days of discontinuing treatment with an MAO inhibitor. Patients previously treated with fluoxetine should discontinue the drug for a minimum of 5 weeks prior to initiating tranylcypromine therapy. At least 2 weeks should be allowed after discontinuing sertraline or paroxetine before starting an MAO inhibitor. Patients discontinuing an SNRI should wait at least 1 week prior to initiating an MAO inhibitor.

Tranylcypromine is contraindicated in combination with buspirone. At least 10 days should elapse between discontinuation of tranylcypromine therapy and initiation of buspirone.

Tranylcypromine is contraindicated in combination with sympathomimetics, including amphetamines which may be found in many herbal preparations as well as over-the-counter drugs such as cold, hay fever, or weight-reducing preparations that contain vasoconstrictors. Use of sympathomimetics and other drugs such as guanethidine, methyldopa, reserpine, dopamine, levodopa, and tryptophan with tranylcypromine may precipitate hypertension, headache, and related symptoms. Cerebral hemorrhage may also occur. The combination of MAO inhibitors and tryptophan has been reported to cause behavioral and neurological syndromes.

Tranylcypromine is contraindicated in combination with meperidine. Meperidine should not be used concomitantly with MAO inhibitors or within 2 or 3 weeks following MAO inhibitor therapy. Serious reactions (including coma, severe hypertension or hypotension, severe respiratory depression, convulsions, malignant hyperpyrexia, excitation, peripheral vascular collapse, and death) have been reported with concomitant use.

Tranylcypromine is contraindicated in combination with dextromethorphan. Brief episodes of psychosis or bizarre behavior have been reported with the combination of MAO inhibitors and dextromethorphan.

Tranylcypromine is contraindicated in combination with cheese or other foods with a high tyramine content. A serious and sometimes fatal hypertensive reaction may occur when excessive amounts of tyramine are consumed in conjunction with tranylcypromine, or within 2 weeks of stopping treatment. Foods with a high tyramine content and that may have been reported to induce a serious hypertensive reaction when consumed with tranylcypromine include all matured or aged cheeses; all aged, cured, or fermented meat, fish, or poultry; all fermented soybean products; sauerkraut; fava or broad bean pods; banana peel (but not the pulp); concentrated yeast extracts; and all tap/draught beers (some bottled beers, including nonalcoholic beer, may also pose a risk). Patients should minimize or avoid all use of alcoholic beverages while taking tranylcypromine. Patients should be instructed to buy and eat only fresh foods or those which have been properly frozen, should avoid eating foods if unsure of storage conditions or freshness, and should be cautious of foods of unknown age or composition even if refrigerated.

Hypertensive crisis (sometimes fatal) is the most important reaction associated with tranylcypromine therapy and is characterized by some or all of the following symptoms: occipital headache that may radiate frontally, palpitation, neck stiffness or soreness, nausea or vomiting, sweating (sometimes with fever and sometimes with cold, clammy skin), pupil dilatation, photophobia, tachycardia or bradycardia, and constricting chest pain. Intracranial bleeding, which can be fatal, has been reported with the paradoxical increase in blood pressure. Hypertensive crises may be precipitated by concomitant administration of sympathomimetic drugs or related compounds, other MAO inhibitors, or dibenzazepine-related entities. Ingestion of foods with a high concentration of tyramine may also cause a hypertensive crisis. Blood pressure should be monitored closely in all patients to detect any pressor response. Patients should be observed frequently, as blood pressure readings should not be relied upon completely. Therapy should be discontinued immediately upon the occurrence of palpitation or frequent headaches, as these signs may be prodromal of a hypertensive crisis.

If a hypertensive crisis occurs, tranylcypromine should be discontinued and therapy to lower blood pressure, usually intravenous phentolamine 5 mg, should be instituted immediately. Do not use parenteral reserpine. Fever should be managed by external cooling.

Tranylcypromine is contraindicated in patients undergoing elective surgery. Elective surgery requiring general anesthesia is not recommended during treatment with tranylcypromine. Concomitant use of cocaine or local anesthesia containing sympathomimetic vasoconstrictors should also be avoided during treatment with tranylcypromine. Additive hypotensive effects may occur when MAO inhibitor therapy is combined with spinal anesthesia. Tranylcypromine should be discontinued at least 10 days prior to any elective surgery.

Tranylcypromine should not be used in combination with some central nervous system depressants such as narcotics and alcohol, or with hypotensive agents. A marked potentiating effect on these classes of drugs has been reported.

Excessive use of caffeine in any form should be avoided in patients receiving tranylcypromine.

Antiparkinsonism drugs should be used with caution in patients receiving tranylcypromine because severe reactions have been reported.

Hypotension may occur during tranylcypromine therapy. Symptoms of postural hypotension are most commonly but not exclusively observed in patients with preexistent hypertension. Blood pressure usually returns rapidly to pretreatment levels upon discontinuation of the drug. At dosages above 30 mg daily, postural hypotension is a major side effect and may result in syncope. Dosage increases should be more gradual for patients showing signs of hypotension at the beginning of therapy. Concomitant administration of tranylcypromine with antihypertensive drugs (including thiazides and diuretics), phenothiazine derivatives, sedatives, or anesthetic drugs may result in additive hypotensive effects.

There have been reports of drug dependency in patients using significantly excessive doses of tranylcypromine. In some cases, there was a history of previous substance abuse. Withdrawal symptoms have included restlessness, anxiety, depression, confusion, hallucination, headache, weakness, and diarrhea. Physicians should carefully evaluate patients for history of drug abuse and follow such patients closely.

Tranylcypromine should be used with caution in the elderly population. Older patients may suffer more morbidity than younger patients during and following an episode of hypertension or malignant hyperthermia, and they may have less compensatory reserve to cope with any serious adverse reaction.

Although excretion of tranylcypromine is rapid, MAO inhibition may persist up to 10 days following discontinuation.

Tranylcypromine should be used with caution in hyperthyroid, diabetic, and epileptic patients. Drugs that lower the seizure threshold, including MAO inhibitors, should not be used with metrizamide. Tranylcypromine should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours after the procedure.

Tranylcypromine is a potent agent which may produce serious side effects. It is not recommended in depressive reactions where other antidepressant agents may be effective. Tranylcypromine should be reserved for patients who can be closely monitored and who have not responded to other, more commonly used antidepressant agents.

Safety and efficacy have not been established in pediatric patients (less than 18 years of age). Tranylcypromine is not approved for use in pediatric patients.

Dialysis

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