Drug Interaction Report

CONTRAINDICATED: The administration of live, attenuated viral or bacterial vaccines during immunosuppressant or intense antineoplastic therapy may be associated with a risk of disseminated infection due to enhanced replication of vaccine virus or bacteria in the presence of diminished immune competence. Patients may be immunosuppressed if they have recently received or are receiving alkylating agents, antimetabolites, radiation, some antirheumatic agents, high dosages of corticosteroids or adrenocorticotropic agents (e.g., greater than or equal to 2 mg/kg/day or 20 mg/day of prednisone or equivalent for 14 consecutive days or more), or long-term topical or inhaled corticosteroids. These patients may also have increased adverse reactions and decreased or suboptimal immunologic response to vaccines.

MANAGEMENT: In general, live attenuated vaccines should not be used in patients receiving immunosuppressive therapy or cancer chemotherapy. Vaccination should be deferred until after such therapy is discontinued and immune function has been restored, usually 4 to 12 weeks after stopping immunosuppressive therapy. A longer waiting period may be necessary following treatment with agents that have a prolonged elimination half-life (e.g., leflunomide, teriflunomide). In most situations, patients who have recently been vaccinated with a live vaccine should not initiate treatment with immunosuppressive therapy for at least 2 weeks (possibly longer in some cases). Current local immunization guidelines and prescribing information for individual vaccines and immunosuppressive agents should be consulted for more specific recommendations. Vaccines may generally be administered to patients receiving corticosteroids as replacement therapy (e.g., for Addison's disease).

ADJUST DOSING INTERVAL: Administration of trifluridine-tipiracil with a standardized high-fat, high-calorie meal has been shown to decrease trifluridine peak plasma concentration (Cmax) as well as tipiracil Cmax and systemic exposure (AUC) by approximately 40% compared to administration in a fasting state in patients with cancer given a single 35 mg/m2 dose. No change in trifluridine AUC was observed.

MANAGEMENT: Based on the observed correlation between increases in the Cmax of trifluridine and decreases in neutrophil counts, trifluridine-tipiracil should be taken within one hour after completion of the morning and evening meals.