Drug Interactions between house dust mite allergen extract and Latuda

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of lurasidone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported for other CYP450 3A4 inhibitors. When a single 10 mg dose of lurasidone was administered with the potent CYP450 3A4 inhibitor ketoconazole (400 mg/day for 5 days), lurasidone peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 6.9- and 9.0-fold, respectively, compared to administration alone. The AUC of lurasidone's active metabolite increased by 6-fold. Another potent CYP450 3A4 inhibitor, posaconazole, has been reported to increase lurasidone AUC by approximately 4.5-fold. When a single 20 mg dose of lurasidone was administered with the moderate CYP450 3A4 inhibitor diltiazem (extended release formulation 240 mg/day for 5 days), lurasidone Cmax and AUC increased by 2.1- and 2.2-fold, respectively, while the AUC of the active metabolite increased by 2.4-fold. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

GENERALLY AVOID: Alcohol may potentiate some of the central nervous system and hypotensive effects of lurasidone. Use in combination may result in increased sedation, dizziness, hypotension, and impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of lurasidone. According to the product labeling, lurasidone mean Cmax and AUC were increased approximately 3-fold and 2-fold, respectively, when administered with food relative to under fasting conditions. Lurasidone AUC was not affected by meal size (in the range of 350 to 1000 calories) or fat content. In clinical studies, lurasidone was administered with food.

MANAGEMENT: Patients treated with lurasidone should avoid consumption of grapefruit and grapefruit juice as well as alcohol. Lurasidone should be taken with food (at least 350 calories).

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.