Cladribine Side Effects

6 ADVERSE REACTIONS The following serious adverse reactions and potential risks are discussed, or discussed in greater detail, in other sections of the labeling: Malignancies [ see Warnings and Precautions (5.1) ] Risk of Teratogenicity [ see Warnings and Precautions (5.2) ] Lymphopenia [ see Warnings and Precautions (5.3)] Infections [ see Warnings and Precautions (5.4) ] Hematologic Toxicity [ see Warnings and Precautions (5.5) ] Graft-Versus-Host Disease With Blood Transfusion [ see Warnings and Precautions (5.6) ] Liver Injury [ see Warnings and Precautions (5.7) ] Hypersensitivity [ see Warnings and Precautions (5.8) ] Cardiac Failure [ see Warnings and Precautions (5.9) ] Most common adverse reactions (incidence > 20%) are upper respiratory tract infection, headache, and lymphopenia.

(6.1) To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp.

at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

In the clinical trial program of cladribine in MS, 1,976 patients received cladribine for a total of 9,509 patient years.

The mean time on study including follow-up was approximately 4.8 years, and approximately 24% of cladribine-treated patients had approximately 8 years of time on study including follow-up.

Of these, 923 patients aged 18 to 66 years received cladribine as monotherapy at a cumulative dose of 3.5 mg per kg.

Table 2 shows adverse reactions in Study 1 [ see Clinical Studies (14) ] with an incidence of at least 5% for cladribine and higher than placebo.

The most common (> 20%) adverse reactions reported in Study 1 are upper respiratory tract infection, headache, and lymphopenia.

Table 2 Adverse Reactions in Study 1 with an Incidence of at Least 5% for Cladribine tablets and Higher than Placebo Cladribine (N=440) % Placebo (N=435) % Upper respiratory tract infection 38 32 Headache 25 19 Lymphopenia 24 2 Nausea 10 9 Back pain 8 6 Arthralgia and arthritis 7 5 Insomnia 6 4 Bronchitis 5 3 Hypertension 5 3 Fever 5 3 Depression 5 3 Hypersensitivity In clinical studies, 11% of cladribine patients had hypersensitivity adverse reactions, compared to 7% of placebo patients [see Warnings and Precautions ( 5.8 )].

Alopecia Alopecia occurred in 3% of cladribine-treated patients compared to 1% of placebo patients.