Drug Interactions between mixed grass pollens allergen extract and safinamide

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.

GENERALLY AVOID: Foods that contain large amounts of tyramine may precipitate a hypertensive crisis in patients treated with safinamide. The proposed mechanism involves potentiation of the tyramine pressor effect due to inhibition of monoamine oxidase (MAO) by safinamide. Monoamine oxidase in the gastrointestinal tract and liver, primarily type A (MAO-A), is the enzyme responsible for metabolizing exogenous amines such as tyramine 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 causing a rise in blood pressure. In vitro, safinamide inhibits MAO-B with greater than 1000-fold selectivity over MAO-A, and neither safinamide nor its major metabolites inhibit MAO-A at clinically relevant concentrations. Results from an oral tyramine challenge study also suggest that safinamide is a selective inhibitor of MAO-B at the recommended dosages of 50 or 100 mg/day. However, this selectivity is not absolute and may diminish in a dose-related manner above the maximum recommended daily dosage. In clinical trials, the incidence of hypertension was 7% and 5% for safinamide 50 mg and 100 mg, respectively, versus 4% for placebo. There were no reported cases of hypertensive crisis.

Administration of safinamide following intake of a high-fat, high-caloric breakfast resulted in a slight delay in the absorption of safinamide, but had no effects on safinamide peak plasma concentration (Cmax) and systemic exposure (AUC) compared to administration under fasted conditions.

MANAGEMENT: Dietary restriction is not ordinarily required during safinamide treatment with respect to most foods and beverages that contain tyramine, which usually include aged, fermented, cured, smoked, or pickled foods (e.g., air-dried and fermented meats or fish, aged cheeses, most soybean products, yeast extracts, red wine, beer, sauerkraut). However, certain foods like some of the aged cheeses (e.g., Boursault, Liederkrantz, Mycella, Stilton) and pickled herring may contain very high amounts of tyramine and could potentially cause a hypertensive reaction in patients taking safinamide, even at recommended dosages, due to increased sensitivity to tyramine. Patients should be advised to avoid the intake of 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, seizures, chest pain, unexplained nausea or vomiting, and stroke-like symptoms. Blood pressure should be regularly monitored and managed accordingly. Medication adjustment may be necessary if blood pressure elevations are sustained or not adequately controlled. Safinamide should not be used at dosages exceeding 100 mg/day, or 50 mg/day in patients with moderate hepatic impairment (Child-Pugh B, 7-9), as it may increase the risk of hypertensive crisis and other adverse reactions associated with nonselective inhibition of MAO. Safinamide can be administered with or without food.