Isocarboxazide

Uses

Isocarboxazide is a monoamine oxidase inhibitor used to treat enduring and debilitating symptoms of depression following inadequate clinical response to other antidepressant drugs.

Isocarboxazide is indicated for the treatment of the enduring and debilitating symptoms of depression that have not responded to other antidepressant drugs. Depression is a common but serious mood disorder. The patient will present changes in its feelings, thoughts, and ability to handle everyday activities. For a mood disorder to be considered as depression, the symptoms should be present for at least two weeks.

Isocarboxazide is also used to associated treatment for these conditions: Depression

How Isocarboxazide works

Isocarboxazide works by irreversibly blocking the action of monoamine oxidases (MAO) in the nervous system. MAO subtypes A and B are involved in the metabolism of serotonin and catecholamine neurotransmitters such as epinephrine, norepinephrine, and dopamine. Isocarboxazide, as a nonselective MAO inhibitor, binds irreversibly to monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B). Isocarboxacid, like other monoamine oxidase inhibitors, are unique psychopharmacological agents whose clinical effect is related to the direct action of the monoamine oxidases to transform them into reactive metabolites.

Toxicity

Long-term toxicity studies to evaluate the carcinogenic, mutagenic and fertility impairment potential have not been conducted.

Food Interaction

• Avoid alcohol. The official product labeling suggests avoiding the use of CNS depressants.
• Avoid tyramine-containing foods and supplements. Foods that contain tyramine include yogurt, aged cheese, ripe bananas, wine, and sourdough bread.
• Limit caffeine intake.

[Major] CONTRAINDICATED: Foods that contain large amounts of tyramine may precipitate a hypertensive crisis in patients treated with monoamine oxidase inhibitors (MAOIs).

The mechanism is inhibition of MAO-A, the enzyme responsible for metabolizing exogenous amines such as tyramine in the gut and preventing them from being absorbed intact.

Once absorbed, tyramine is metabolized to octopamine, a substance that is believed to displace norepinephrine from storage granules.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of MAOIs.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: In general, patients treated with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, linezolid, procarbazine) should avoid consumption of products that contain large amounts of amines and protein foods in which aging or breakdown of protein is used to increase flavor.

These foods include cheese (particularly strong, aged or processed cheeses), sour cream, wine (particularly red wine), champagne, beer, pickled herring, anchovies, caviar, shrimp paste, liver (particularly chicken liver), dry sausage, salamis, figs, raisins, bananas, avocados, chocolate, soy sauce, bean curd, sauerkraut, yogurt, papaya products, meat tenderizers, fava bean pods, protein extracts, yeast extracts, and dietary supplements.

Caffeine may also precipitate hypertensive crisis so its intake should be minimized as well.

At least 14 days should elapse following discontinuation of MAOI therapy before these foods may be consumed.

Specially designed reference materials and dietary consultation are recommended so that an appropriate and safe diet can be planned.

Patients should be advised to promptly seek medical attention if they experience potential signs and symptoms of a hypertensive crisis such as severe headache, visual disturbances, difficulty thinking, stupor or coma, seizures, chest pain, unexplained nausea or vomiting, and stroke-like symptoms.

Patients should also be counseled not to use MAOIs with alcohol, and to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them.

Isocarboxazide Drug Interaction

Major: citalopram, citalopram, duloxetine, duloxetine, trazodone, trazodone, venlafaxine, venlafaxine, amitriptyline, amitriptyline, escitalopram, escitalopramModerate: fluticasone / salmeterol, fluticasone / salmeterol, contained in alcoholic beverages , contained in alcoholic beverages , zolpidem, zolpidem, paliperidone, paliperidone

Isocarboxazide Disease Interaction

Major: blood pressure, carcinoid syndrome, headaches, hyperthyroidism, liver disease, pheochromocytoma, renal dysfunction, alcohol, depression, hypertension/CVD, liver disease, pheochromocytoma, severe renal diseaseModerate: hepatotoxicity, hyperthyroidism, hypoglycemia, parkinsonism, schizophrenia/bipolar, seizures, angina, bipolar disorder screening, diabetes, hypotension, renal disease, schizophrenia, seizures

Elimination Route

The pharmacokinetic profile of isocarboxazid have not been fully studied but it is suggested that its properties should be fairly similar to the ones of some analogs like phenelzine and tranylcypromine. These drugs are readily absorbed by the GI tract, present a low bioavailability and reach peak concentrations in 1-2 hours.

Half Life

The pharmacokinetic profile of isocarboxazid have not been fully studied but it is suggested that its properties should be fairly similar to the ones of some analogs like phenelzine and tranylcypromine. The isocarboxazid half-life is of little interest as it is an irreversible monoamine oxidase inhibitor. These drugs present a very short half-life of 1.5-4 hours due to rapid hepatic metabolism.

Elimination Route

Most of the eliminated dose is found in the urine, accounting for the 42.5% of the administered dose after 24 hours. From this amount, 75% of the renally eliminated drug is in the form of hippuric acid. Another section of the eliminated dose is observed through the intestinal tract and it accounts for 22% of the administered dose after 24 hours.

Innovators Monograph

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