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.

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of trabectedin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

GENERALLY AVOID: Coadministration of trabectedin with other agents known to induce hepatotoxicity such as alcohol may potentiate the risk of liver injury. Reversible, acute increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have occurred frequently in patients treated with trabectedin alone or with pegylated liposomal doxorubicin in clinical trials. In one U.S. trial with 378 patients, grade 3 or 4 elevated liver function tests (defined as elevations in ALT, AST, total bilirubin, or alkaline phosphatase) were reported in 35% of patients receiving trabectedin. ALT or AST elevations greater than eight times the upper limit of normal (ULN) occurred in 18% of patients, and drug-induced liver injury (defined as concurrent elevations in ALT or AST more than three times ULN, alkaline phosphatase less than two times ULN, and total bilirubin at least two times ULN) occurred in 1.3% of patients.

MANAGEMENT: Consumption of grapefruit or grapefruit juice during treatment with trabectedin should be avoided. Excessive use of alcohol is also not recommended. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Monitoring of alkaline phosphatase, bilirubin, AST, and ALT should occur regularly during trabectedin treatment in accordance with the product labeling, or as often as necessary when clinical symptoms develop. Trabectedin must not be used in patients with elevated bilirubin at the time of initiation of cycle. Elevated liver function tests should be managed with treatment interruption, dosage reduction, or permanent discontinuation depending on the severity and duration of abnormality.