isocarboxazid

isocarboxazid /iso·car·box·a·zid/ (i″so-kahr-bok´sah-zid) a monoamine oxidase inhibitor used as an antidepressant and in the prophylaxis of migraine.

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isocarboxazid

[-kärbok′səzid]

a monoamine oxidase inhibitor.

indication It is prescribed in the treatment of mental depression.

contraindications Liver or kidney dysfunction; congestive heart failure; pheochromocytoma; concomitant use of a sympathomimetic drug or foods high in tryptophan, tyramine, or caffeine; or known hypersensitivity to the drug prohibits its use. Must be used with caution in patients with suicidal ideation.

adverse effects Among the more serious adverse effects are hyperactivity, cardiac arrhythmia, hypotension, vertigo, dryness of mouth, constipation, and blurred vision. Monoamine oxidase inhibitors produce many adverse drug interactions.

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isocarboxazid

Marplan

Pharmacologic class: MAO inhibitor

Therapeutic class: Antidepressant

Pregnancy risk category C

FDA Boxed Warning

• Drug may increase risk of suicidal thinking and behavior in children and adolescents with major depressive disorder and other psychiatric disorders, especially during first few months of therapy. Risk must be balanced with clinical need, as depression itself increases suicide risk. With patient of any age, observe closely for clinical worsening, suicidality, and unusual behavior changes when therapy begins. Advise family and caregivers to observe patient closely and communicate with prescriber as needed.
• Drug isn't approved for use in pediatric patients.

Action

Nonselectively inhibits hydrazine MAO, an enzyme system thought to raise biogenic amine levels in brain

Availability

Tablets: 10 mg

⊘Indications and dosages

➣ Depression

Adults: Initially, 10 mg P.O. b.i.d. If tolerated, may increase in increments of 1 tablet q 2 to 4 days, to achieve dosage of 4 tablets/day by end of week. May then increase in increments of up to 20 mg/week, if needed and tolerated, to a maximum of 60 mg/day given in two to four divided doses. Once maximum clinical response occurs, dosage may be lowered slowly over several weeks if it doesn't jeopardize therapeutic response.

Contraindications

• Hypersensitivity to drug
• Concurrent use of other MAO inhibitors, dibenzazepine derivatives, selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), sympathomimetics (including amphetamines), certain CNS depressants (including opioids), sedatives, antihypertensives, antihistamines, thiazide diuretics, anesthetics, bupropion, buspirone, or dextromethorphan
• Known or suspected cerebrovascular defect
• Hypertension, cardiovascular disease
• Severe or frequent headache
• Pheochromocytoma
• Hepatic disease, abnormal liver function tests
• Renal disease
• Consumption of tyramine-rich foods (such as aged cheeses) or excessive amounts of caffeine

Precautions

Use cautiously in:
• hyperthyroidism, seizure disorders, hypotension, diabetes mellitus, myocardial ischemia, hypomania
• patients switching MAO inhibitors
• suicidal or drug-dependent patients
• elderly patients
• pregnant or breastfeeding patients
• children younger than age 16 (safety and efficacy not established).

Administration

☞ If hypertensive crisis occurs, withdraw drug immediately and give phentolamine 5 mg I.V. slowly, as ordered.
☞ Ask patient about other drugs he's using. MAO inhibitors can cause dangerous interactions with many drugs.
☞ Know that psychotropics should be withheld for 14 days after isocarboxazid withdrawal.

Route	Onset	Peak	Duration
P.O.	Unknown	Unknown	Unknown

Adverse reactions

CNS: drowsiness, anxiety, forgetfulness, hyperactivity, lethargy, sedation, syncope, headache, insomnia, sleep disturbance, tremor, myoclonic jerks, paresthesia, dizziness, suicidal behavior or ideation (especially in child or adolescent)

CV: orthostatic hypotension, palpitations, hypertensive crisis

GI: nausea, diarrhea, constipation, dry mouth

GU: urinary frequency, urinary hesitancy, erectile dysfunction Hepatic: jaundice, hepatotoxicity

Musculoskeletal: heavy feeling

Skin: sweating

Other: chills

Interactions

Drug-drug. Amphetamines, CNS depressants, dextromethorphan, dibenzazepine derivatives and other TCAs, other MAO inhibitors, SSRIs (such as fluoxetine, paroxetine), sympathomimetics: hypertensive crisis, seizures, fever, diaphoresis, excitation, delirium, tremor, coma, circulatory collapse

Anesthetics: severe hypotension

Antidepressants, bupropion, buspirone: hypertension

Antihypertensives, beta-adrenergic blockers, thiazide diuretics: increased hypotensive effects

Dextromethorphan, tryptophan: hypertension, excitation, hyperpyrexia

Disulfiram: severe toxicity

Epinephrine, guanadrel, guanethidine, norepinephrine, reserpine, vasoconstrictors: hypertensive crisis

Insulin, oral hypoglycemics: additive hypoglycemia

Meperidine: severe hypertension or hypotension, respiratory depression, seizures, malignant hyperpyrexia, excitation, peripheral vascular collapse, coma, death

Drug-diagnostic tests. Liver function tests: altered results

Drug-food. Excessive caffeine consumption: nervousness, shakiness, rapid heartbeat, anxiety

Foods high in tyramine, such as cheese (especially aged cheeses), sour cream, Chianti wine, sherry, beer (including nonalcoholic beer), liqueurs, pickled herring, anchovies, caviar, liver, canned figs, raisins, bananas, avocados, soy sauce, sauerkraut, pods of broad beans (such as fava beans), yeast extracts, yogurt, meat extracts, meat prepared with tenderizers, dry sausage: hypertensive crisis

Drug-behaviors. Alcohol use: potential for severe hypertension, excitation, seizures, delirium, hyperpyrexia, circulatory collapse, coma, death

Patient monitoring

☞ Monitor blood pressure frequently. Drug may cause hypertensive crisis.
☞ Watch for increased depression and suicidal ideation, especially in child or adolescent.
☞ Monitor liver function tests. Assess for jaundice and signs and symptoms of hepatic dysfunction; discontinue drug and notify prescriber if these occur.

Patient teaching

• Explain importance of taking drug exactly as prescribed.
☞ Caution patient not to stop therapy suddenly. Dosage must be tapered.
☞ Instruct patient to immediately report occipital headache, palpitations, stiff neck, nausea, sweating, dilated pupils, and photophobia (indications of hypertensive crisis).
☞ Tell patient to immediately report rash, hives, itching, shortness of breath, wheezing, cough, or swelling of face, lips, tongue, or throat.
☞ Advise patient (or caregiver, as appropriate) to monitor his mental status carefully and immediately report increased depression or suicidal thoughts or behavior (especially in child or adolescent).
☞ Stress importance of avoiding certain foods and beverages (especially those containing tyramine) and over-the-counter preparations during and for 14 days after therapy. Inform patient that pharmacist can provide complete list of foods to avoid.
• Instruct patient to tell all prescribers he's taking drug.
☞ Caution patient not drink alcohol or consume excessive amounts of caffeine.
• Advise patient to rise slowly from a lying or sitting position, to avoid dizziness.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration, vision, and alertness.
• Tell patient to discontinue drug at least 10 days before elective surgery.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and behaviors mentioned above.