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. 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 (see Precautions).
List of adverse reactions: Adverse reactions described in the list as follows are derived from pooled data from clinical studies in MS in which oral cladribine was used as monotherapy at a cumulative dose of 3.5 mg/kg. The safety database from these studies comprises 923 patients.
The following definitions apply to the frequency terminology used hereafter: 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 (see Precautions).
Blood and lymphatic system disorders: Very common: Lymphopenia. Common: Decrease in neutrophil count.
Skin and subcutaneous tissue disorders: Common: Rash, alopecia.
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 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 (see Precautions) and strict criteria for initiating and continuing cladribine treatment must be followed (see Dosage & Administration).
Malignancies: In clinical studies and long-term follow-up of patients treated with a cumulative dose of 3.5 mg/kg oral cladribine, events of malignancies were observed more frequently in cladribine-treated patients (10 events in 3,414 patient-years [0.29 events per 100 patient-years]) compared to patients who received placebo (3 events in 2,022 patient-years [0.15 events per 100 patient-years]) (see Precautions).