Drug Interactions between mixed grass pollens allergen extract and rasagiline

GENERALLY AVOID: Foods that contain large amounts of tyramine may precipitate a hypertensive crisis in patients treated with monoamine oxidase (MAO) inhibitors. The mechanism involves 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. Although rasagiline is a selective inhibitor of MAO-B at the recommended dosages of 0.5 or 1 mg/day, selectivity is not absolute and may diminish with increasing dosage. There were no cases of hypertensive crisis in the clinical development program associated with rasagiline treatment at 1 mg/day, in which most patients did not follow dietary tyramine restriction. However, rare cases of hypertensive crisis have been reported during the postmarketing period in patients who ingested unknown amounts of tyramine-rich foods while taking recommended dosages of rasagiline or selegiline, another MAO-B inhibitor.

Rasagiline peak plasma concentration (Cmax) and systemic exposure (AUC ) are decreased by approximately 60% and 20%, respectively, during coadministration with a high-fat meal. The time to peak concentration (Tmax) is not affected by food.

MANAGEMENT: Dietary restriction is not ordinarily required during rasagiline treatment with respect to most foods and beverages that may contain tyramine such as air-dried and fermented meats or fish, aged cheeses, most soybean products, yeast extracts, red wine, beer, and sauerkraut. However, certain foods like some of the aged cheeses (e.g., Boursault, Liederkrantz, Mycella, Stilton) may contain very high amounts of tyramine and could potentially cause a hypertensive reaction in patients taking rasagiline even at recommended dosages due to increased sensitivity to tyramine. Patients should be advised to avoid ingesting very high levels of tyramine (e.g., greater than 150 mg), and to promptly seek medical attention if they experience potential signs and symptoms of a hypertensive crisis such as severe headache, visual disturbances, confusion, stupor or coma, seizures, chest pain, unexplained nausea or vomiting, and stroke-like symptoms. Rasagiline should not be used at dosages exceeding 1 mg/day (0.5 mg/day for patients with mild hepatic impairment or concomitant use of ciprofloxacin or other CYP450 1A2 inhibitors), as it can increase the risk of hypertensive crisis and other adverse reactions associated with nonselective inhibition of MAO. Rasagiline can be administered with or without food.

ADJUST DOSING INTERVAL: Since sublingual preparations of allergenic extracts are meant to be absorbed directly from tissues under the tongue into the blood stream, consuming food or beverage during or immediately after administration may reduce the systemic bioavailability of the medication.

MONITOR: Coadministration of allergenic extracts for allergy immunotherapy with alcohol may potentiate the risk of allergic reactions, including anaphylaxis. According to some studies, alcohol is an augmenting factor influencing immunological mechanisms that can induce more severe allergic reactions and is involved in up to 15% of cases of anaphylactic reactions. Proposed mechanisms include an increase in allergen absorption from altered permeability of the intestinal epithelial barrier, enhancing mast cell and basophil activation, and an increase in serum IgE concentrations. A causal relationship with all allergenic extracts has not been established.

MANAGEMENT: Food or beverage should not be taken with, or for at least 5 minutes after, the administration of sublingual allergenic extracts. Patients should also avoid swallowing for about 1 minute following placement of the allergen extract under the tongue. Caution is advised if allergenic extracts for immunotherapy are used concomitantly with alcohol. Some manufacturers of peanut allergen extract recommend alcohol not be consumed for 2 hours before, or 2 hours after taking peanut allergen extract and if alcohol use cannot be avoided, that withholding or decreasing peanut allergen dosage should be considered. Individual prescribing information should be consulted for further guidance and clinical monitoring may be considered.