1 INDICATIONS AND USAGE Cladribine tablets are indicated for the treatment of relapsing form of multiple sclerosis (MS), to include relapsing-remitting disease in adults.

Because of its safety profile, use of cladribine tablets is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS [ see Warnings and Precautions (5) ].

Limitations of Use Cladribine tablets are not recommended for use in patients with clinically isolated syndrome (CIS) because of its safety profile [ see Warnings and Precautions (5) ].

Cladribine tablets are purine antimetabolite indicated for the treatment of relapsing form of multiple sclerosis (MS), to include relapsing-remitting disease in adults.

Because of its safety profile, use of cladribine tablets are generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS.

( 1 , 5 ) Limitations of Use Cladribine tablets are not recommended for use in patients with clinically isolated syndrome (CIS) because of its safety profile.

( 1 , 5 )

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.

Myelodysplastic Syndrome Cases of myelodysplastic syndrome have been reported in patients that had received parenteral cladribine at a higher dosage than that approved for cladribine.

These cases occurred several years after treatment.

Herpes Meningoencephalitis Fatal herpes meningoencephalitis occurred in one cladribine-treated patient, at a higher dosage and longer duration of therapy than the approved cladribine dosage and in combination with interferon beta-1a treatment.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) SJS and TEN are identified risks of parenteral cladribine for the treatment of oncologic indications.

Seizures In clinical studies, serious events of seizure occurred in 0.3% of cladribine-treated patients compared to 0 placebo patients.

Serious events included generalized tonic-clonic seizures and status epilepticus.

It is unknown whether these events were related to the effects of multiple sclerosis alone, to cladribine, or to a combination of both.

6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of cladribine.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Infections and Infestations: nocardiosis, varicella zoster, histoplasmosis, cryptococcosis, and toxoplasmosis [see Warnings and Precautions ( 5.4 )].

Hepatobiliary Disorders: liver injury [see Warnings and Precautions ( 5.7 )]