Warnings and precautions

• It is expected that most patients with Grade 3 or 4 lymphopenia recover to either normal lymphocyte counts or Grade 1 lymphopenia within 9 months
• To decrease the risk for severe lymphopenia, lymphocyte counts must be determined before, during and after MAVENCLAD treatment
• If lymphocyte counts drop below 500 cells/mm³, active monitoring is recommended until values increase above 500 cells/mm³  

• MAVENCLAD is contraindicated in patients at an increased risk of opportunistic infections and in patients with active infections, including active chronic bacterial, fungal or viral infections
  
• MAVENCLAD increases the risk of infections, especially in patients who develop severe lymphopenia. The increased risk of infections may persist until recovery of lymphopenia
• Latent infections may be activated; therefore, screening for latent infections is recommended prior to initiation of therapy in year 1 and year 2, and a delay in initiation of treatment is recommended until the infection is adequately treated
• A delay in initiation of MAVENCLAD should also be considered in patients with an acute infection until the infection is fully controlled

Herpes zoster¹

• In two clinical studies, the rate of herpes zoster infection was 2.0% for MAVENCLAD patients vs. 0.2% for placebo
• All cases of herpes zoster in patients receiving MAVENCLAD were localized (dermatomal) in nature
• Herpes zoster infection was more likely to occur during periods of Grade 3/4 lymphopenia
• Patients with lymphocyte counts below 500 cells/mm³ should be actively monitored for signs and symptoms suggestive of infection
• If lymphocyte counts drop below 200 cells/mm³, anti-herpes prophylaxis should be considered during the time of Grade 4 lymphopenia  

• In two clinical studies, malignancies were reported in 5/662 (0.76%) patients receiving MAVENCLAD and in 0/641 (0%) patients on placebo
• Patients with prior malignancy were excluded from participating in the clinical development program
• MAVENCLAD is contraindicated in patients with MS with active malignancies
  

1. MAVENCLAD™ Product Monograph. EMD Serono. November 2017.