ed patients had hypersensitivity reactions,compared to 7% of placebo patients. Hypersensitivity reactions that were serious and/or led todiscontinuation of MAVENCLAD (e.g., dermatitis, pruritis) occurred in 0.5% ofMAVENCLAD-treated patients, compared to 0.1% of placebo patients. One patient had aserious hypersensitivity reaction with rash, mucous membrane ulceration, throat swelling,vertigo, diplopia, and headache after the first dose of MAVENCLAD.
If a hypersensitivity reaction is suspected, discontinue MAVENCLAD therapy. Do not useMAVENCLAD in patients with a history of hypersensitivity to cladribine [see Contraindications(4)].
5.9 Cardiac Failure
In clinical studies, one MAVENCLAD-treated patient experienced life-threatening acute cardiacfailure with myocarditis, which improved after approximately one week. Cases of cardiac failurehave also been reported with parenteral cladribine used for treatment indications other thanmultiple sclerosis.
Instruct patients to seek medical advice if they experience symptoms of cardiac failure (e.g.,shortness of breath, rapid or irregular heartbeat, swelling).
6 ADVERSE REACTIONS
The following serious adverse reactions and potential risks are discussed, or discussed in greaterdetail, 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)]
6.1 Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction ratesobserved in the clinical trials of a drug cannot be directly compared to rates in the clinical studiesof 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 of9,509 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 studyincluding follow-up. Of these, 923 patients aged 18 to 66 years received MAVENCLAD asmonotherapy 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 atleast 5% for MAVENCLAD and higher than placebo. The most common (> 20%) adversereactions 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
MAVENCLAD and Higher than Placebo
MAVENCLAD
(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 MAVENCLAD patients had hypersensitivity adverse reactions,compared to 7% of placebo patients [see Warnings and Precautions (5.8)].
Alopecia
Alopecia occurred in 3% of MA |
