isocarboxazid (Rx)

Frequency Not Defined

Common

• Orthostatic hypotension
• Dizziness
• Drowsiness
• Fatigue
• Headache
• Hyperreflexia
• Sleep disturbance
• Weakness
• Tremor
• Constipation
• Dry mouth

Less Common

• Confusion
• Decreased memory
• Paresthesia
• Anorexia
• Nausea
• Vomiting
• Impotence
• Urinary frequency or retention
• Nystagmus

Uncommon

• Edema
• Anxiety
• Hypomania
• Irritation
• Hypermetabolic syndrome (hyperpyrexia, tachycardia, tachypnea, incr CPK, acidosis)
• SIADH
• Arthralgia

Rare

• Risk of hypertensive crisis (usually due to drug interaction)
• Ataxia
• Seizure
• Jaundice
• Visual disturbance

Contraindications

Hypersensitivity

Pheochromocytoma, CHF, CVD, severe renal impairment

Confirmed or suspected cerebrovascular defect or any patient with cardiovascular disease, hypertension, or history of headache

Schizophrenia

History of liver disease or abnormal liver function tests

Concurrent administration with MAO inhibitors or dibenzazepine derivatives; sympathomimetics (including amphetamines); some central nervous system depressants (including narcotics and alcohol); antihypertensive, diuretic, antihistaminic, sedative or anesthetic drugs, bupropion (within 14 days of isocarboxazid discontinuation), buspirone (<10 days of isocarboxazid discontinuation), dextromethorphan, cheese or other foods with a high tyramine content; or excessive quantities of caffeine

Use with SSRIs (<14 days of discontinuing isocarboxazid; wait 5 weeks between discontinuation of fluoxetine and initiation of isocarboxazid)

Use with MAO inhibitors (wait 1 week between discontinuation of MAO inhibitor and initiation of isocarboxazid)

Concurrent use with CNS depressants may result in delirium, hyperpyrexia, seizures, coma, excitation, and hyper/hypotension

Consumption of foods high in tyramine or supplements containing caffeine, tyrosine, tryptophan, phenylalanine, or phenylalanine (Hypertensive reactions may occur)

Within 10 days of a surgery requiring general anesthesia

Concurrent administration with furazolidone, pargyline, pargyline and methyclothiazide, phenelzine sulfate, procarbazine, tranylcypromine sulfate, dibenzazepine-related and other tricyclics, amitriptyline, perphenazine and amitriptyline, clomipramine hydrochloride, desipramine, imipramine, nortriptyline, protriptyline, doxepin, carbamazepine, cyclobenzaprine, amoxapine, maprotiline, trimipramine maleate

Concomitant administration with meperidine or within 2-3 weeks following MAO therapy

Cautions

Use caution with doses >40 mg/day

Clinical worsening & suicide ideation may occur despite medication in adolescents & young adults (18-24 years)

Caution in patients with diabetes mellitus (monitor glucose closely), glaucoma, hepatic/renal impairment, thyroid dysfunction

Therapy can cause serious side effects; not recommended as initial therapy; should be reserved for patients who have not responded satisfactorily to other antidepressants

Hypotension may occur; seen most commonly in patients with preexistent hypertension; blood pressure usually returns rapidly to pretreatment levels upon discontinuation of drug; dosage increases should be made more gradually in patients showing a tendency toward hypotension at beginning of therapy; postural hypotension may be relieved by having the patient lie down until blood pressure returns to normal

Therapy lowers convulsive threshold in some animal experiments, use caution if epileptic patients treated; therapy appears to have varying effects in epileptic patients; while some have a decrease in frequency of seizures, others have more seizures; discontinue at least 48 hours before myelography; should not resume therapy for at least 24 hours postprocedure

There is low incidence of altered liver function or jaundice in patients receiving therapy; periodic liver chemistry tests should be performed during therapy; discontinue use at first sign of hepatic dysfunction or jaundice

MAO inhibitors can suppress anginal pain that would otherwise serve as a warning of myocardial ischemia

Use cautiously in hyperactive or agitated patients, as well as in schizophrenic patients; may cause excessive stimulation; activation of mania/hypomania reported in a small proportion of patients with major affective disorder who were treated with marketed antidepressants

Hypertensive crisis

• Hypertensive crisis associated with MAO inhibitors use, which can be fatal; may result from co-administration of MAOIs and certain drugs and foods; monitor blood pressure should closely to detect any pressor response; discontinue therapy immediately if palpitations or frequent headaches occur; these symptoms may be prodromal of a hypertensive crisis
• If hypertensive crisis occurs, institute therapy to lower blood pressure

Bipolar disorder

• A major depressive episode may be the initial presentation of bipolar disorder; treating such an episode with an antidepressant alone may increase likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder
• Prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression
• Drug is not approved for use in treating bipolar depression

Pregnancy

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants, during pregnancy; healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844405-6185 or visiting online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants

The potential reproductive toxicity of the drug has not been adequately evaluated in animals; it is also not known whether isocarboxazid can cause embryo/fetal harm when administered to a pregnant woman or can affect reproductive capacity; drug should be given to a pregnant woman only if clearly needed

Lactation

Levels of excretion in human milk have not been determined, and effects on nursing infant are unknown; therapy should be used in women who are nursing only if clearly needed

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Nonselective monoamine oxidase inhibitor; may inhibit the enzyme monoamine oxidase, which is responsible for the breakdown of dopamine, serotonin, epinephrine, and norepinephrine, in turn causing an increase in endogenous concentrations of these neurotransmitters.

Pharmacokinetics

Effects may continue up to 2 wk after discontinuation