Drug Interaction Report

ADJUST DOSING INTERVAL: The administration of inactivated, killed, or otherwise noninfectious vaccines during siponimod therapy is generally safe, but may be associated with a diminished or suboptimal immunologic response. The proposed mechanism is a dose-dependent reduction of peripheral blood lymphocyte counts by siponimod, that may persist for up to 3-4 weeks after the last dose, potentially reducing the immunologic response to vaccination. The effects of siponimod (2 mg daily) on the immune response to T-cell dependent (quadrivalent influenza vaccine) and T-cell independent (pneumococcal polysaccharide vaccine, PPV-23) vaccinations were evaluated in a study of healthy subjects (n=120). No clinically relevant effects were noted on the antibody response to PPV-23 in patients taking concurrent siponimod. However, concomitant siponimod or siponimod treatment pauses ranging from 10 days before until 14 days after the influenza vaccination were associated with 15% to 30% lower rates of seroconversion when compared with placebo. Clinical data is not available for all inactivated, killed, or otherwise noninfectious vaccines with siponimod.

MANAGEMENT: Immune response to vaccines may be reduced during and for up to one month after discontinuation of siponimod therapy. Some authorities suggest pausing siponimod treatment for 1 week prior to, and 4 weeks after certain planned vaccinations. This recommendation may not apply to the PPV-23 vaccine based on available data. The decision to pause siponimod treatment must evaluate the benefits and risks to the patient and may require a re-titration of siponimod dosing. Consultation with the package labeling may be advisable.