Drug Interaction Report

MONITOR CLOSELY: The use of alemtuzumab with other immunosuppressive or antineoplastic agents may increase the risk of infections. Alemtuzumab reduces T and B lymphocytes, but the extent and duration of the reduction is expected to differ based on the dose and indication. Alone, alemtuzumab may cause severe and prolonged myelosuppression, lymphopenia, and rarely, fatal autoimmune cytopenias. Serious, sometimes fatal opportunistic infections have been reported, and the risk may theoretically increase when coadministered with other immunosuppressive therapy. Agents that may be significantly myelo- or immunosuppressive include antineoplastic agents, radiation, zidovudine, linezolid, some antirheumatic agents, high dosages of corticosteroids or adrenocorticotropic agents (greater than 10 mg/day to 1 mg/kg/day, whichever is less, of prednisone or equivalent for more than 2 weeks), and long-term topical or inhaled corticosteroids.

MANAGEMENT: Caution is advised if alemtuzumab must be used in patients who have recently received or are receiving treatment with other immunosuppressive or antineoplastic drugs, and vice versa. Some authorities consider the combination of alemtuzumab (marketed under the brand name Lemtrada) to be contraindicated in patients receiving antineoplastic or immunosuppressive therapies. Close clinical and laboratory monitoring should be completed as recommended by the manufacturer. The product labeling should be consulted for recommendations on anti-infective prophylaxis to minimize the risks of serious opportunistic infections; as well as, for dosing adjustments and discontinuation recommendations should other toxicities or adverse effects occur. Some authorities recommend that alemtuzumab, marketed under the brand name Campath, not be given within 3 weeks of other chemotherapeutic agents. Since higher dosages are associated with an increased incidence of pancytopenia, the manufacturer of this dosage form of alemtuzumab recommends that single doses not exceed 30 mg and cumulative weekly doses not exceed 90 mg.

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of albendazole, which is rapidly converted by hepatocytes and intestinal mucosal cells into the active metabolite, albendazole sulfoxide (ABZSX), following absorption. The proposed mechanism is stimulation of gastric acid secretion, as the absorption of albendazole is thought to be pH-dependent. According to the product labeling, plasma concentrations of ABZSX are up to 5-fold higher on average when albendazole is administered with a fatty meal (fat content approximately 40 g) compared to administration in the fasted state. In one study of six healthy male volunteers, administration of a single 10 mg/kg oral dose of albendazole in combination with a high-fat meal (57 g fat, 1399 kcal) increased the mean ABZSX peak plasma concentration (Cmax) and systemic exposure (AUC) by 6.5- and 9.4-fold, respectively, and delayed the time to reach Cmax (Tmax) from 2.5 to 5.3 hours compared to administration in the fasted state with water. The elimination half-life was not affected.

MONITOR: Grapefruit juice may increase the oral bioavailability of albendazole, which is rapidly converted by hepatocytes and intestinal mucosal cells into the active metabolite, albendazole sulfoxide (ABZSX), following absorption. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In six healthy male volunteers, administration of a single 10 mg/kg oral dose of albendazole in combination with 250 mL of double-strength grapefruit juice increased the mean ABZSX peak plasma concentration (Cmax) and systemic exposure (AUC) by 3.2- and 3.1-fold, respectively, compared to administration with water. However, because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: To ensure maximal oral absorption, albendazole should be taken with food. Grapefruit juice may also enhance the oral bioavailability of albendazole.