Mavenclad Adverse Reactions

Summary of the safety profile: The most clinically relevant adverse reactions reported in MS patients who received cladribine at the recommended cumulative dose of 3.5 mg/kg over 2 years in clinical studies were lymphopenia and herpes zoster (refer to Haematological Monitoring and Infections under Precautions). Lymphopenia led to treatment discontinuation in a phase 3 trial (CLARITY trial) in approximately 2.2% of patients. The incidence of herpes zoster was higher during the period of grade 3 or 4 lymphopenia (< 500 to 200 cells/mm³ or < 200 cells/mm³) compared to the time when the patients were not experiencing grade 3 or 4 lymphopenia.
List of adverse reactions: Listed as follows are adverse reactions (i.e. causal association with the treatment is considered at least possible) derived from clinical studies with MAVENCLAD in MS, including those with lower incidence than 5%.
The following definitions apply to the frequency terminology: Very common: ≥ 1/10; Common: ≥ 1/100 to < 1/10; Uncommon: ≥ 1/1,000 to < 1/100; Rare: ≥ 1/10,000 to < 1/1,000; Very rare: < 1/10,000; Frequency not known: cannot be estimated from the available data.
Infections and infestations: Common: Oral herpes, dermatomal herpes zoster.
Very rare: Tuberculosis.
Blood and lymphatic system disorders: Very common: Lymphopenia, which may be severe (grade 3 or 4).
Common: Decrease in neutrophil count.
Skin and subcutaneous tissue disorders: Common: Rash (e.g. pustular, papular, macular, pruritic, erythematous rash), alopecia.
Postmarketing experience: Immune system disorders: Common: hypersensitivity including pruritus urticaria, rash and rare cases of angio-oedema.
Hepatobiliary disorders: Uncommon: Liver Injury.
Description of selected adverse reactions: Lymphopenia: In clinical studies, 20% to 25% of the patients treated with a cumulative dose of cladribine 3.5 mg/kg over 2 years as monotherapy developed transient grade 3 or 4 lymphopenia. Grade 4 lymphopenia was seen in less than 1% of the patients. The largest proportion of patients with grade 3 or 4 lymphopenia was seen 2 months after the first cladribine dose in each year (4.0% and 11.3% of patients with grade 3 lymphopenia in year 1 and year 2, 0% and 0.4% of patients with grade 4 lymphopenia in year 1 and year 2). It is expected that most patients with grade 3 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 cladribine treatment and strict criteria for initiating and continuing cladribine treatment must be followed (refer to Precautions and Dosage & Administration).
Liver Injury: During post-marketing experience, uncommon events of liver injury, including serious cases and cases leading to discontinuation of treatment, were reported in temporal association with MAVENCLAD.
Transient elevations of serum transaminases were usually greater than 5-fold the upper limit of normal (ULN). Isolated cases of transient serum transaminase elevations up to 40-fold the ULN and/or symptomatic hepatitis with transient elevation of bilirubin and jaundice have been observed.