The safety and tolerability of MAVENCLAD were studied in CLARITY.1
The most common (>20%) adverse reactions reported in CLARITY are upper respiratory tract infection, headache, and lymphopenia.1
In the pivotal trial, 3.5% of patients receiving MAVENCLAD discontinued treatment due to adverse reactions vs 2.1% of patients receiving placebo.2
92% of patients treated with MAVENCLAD completed the full 96 weeks of the study vs 87% of patients receiving placebo.1
In patients treated with parenteral cladribine for oncologic indications, cases of progressive multifocal leukoencephalopathy (PML) have been reported in the postmarketing setting.
In the all-exposed cohort, the incidence of autoimmune diseases was similar between the cladribine group (0.58 events per 100 patient-years) and the placebo group (0.73 events per 100 patient-years).
MAVENCLAD causes a dose-dependent reduction in lymphocyte count. In clinical studies, 87% of MAVENCLAD-treated patients experienced lymphopenia. The lowest absolute lymphocyte counts occurred approximately 2 to 3 months after the start of each treatment course and were lower with the second treatment course.1
In patients treated with MAVENCLAD 3.5 mg/kg as monotherapy:
The incidence of lymphopenia <500 cells/μL was higher in patients who had used drugs to treat relapsing forms of MS prior to study entry (32.1%), compared to those with no prior use of these drugs (23.8%).1
Lymphocytes must be within normal limits before initiating the first treatment course and at least 800 cells/μL before initiating the second treatment course. If necessary, delay the second treatment course for up to 6 months to allow for recovery of lymphocytes to at least 800 cells/μL. If this recovery takes more than 6 months, the patient should not receive further treatment with MAVENCLAD.1
The most frequent serious infections in MAVENCLAD patients included herpes zoster and pyelonephritis.
Treatment with MAVENCLAD may increase the risk of malignancy. MAVENCLAD is contraindicated in patients with current malignancy.1
Malignancy cases in MAVENCLAD patients occurred in several different trials. In the CLARITY MAVENCLAD group, 6 patients (1.4%) experienced malignancies compared to 0 patients in the placebo group.2
Malignancy cases in MAVENCLAD patients included metastatic pancreatic carcinoma, malignant melanoma (2 cases), and ovarian cancer, compared to malignancy cases in placebo patients, all of which were curable by surgical resection (basal cell carcinoma, cervical carcinoma in situ [2 cases]).1
There were no cases of hematological or lymphoproliferative cancers in the pooled safety dataset.3
Treatment with MAVENCLAD may increase the risk of malignancy.1 In controlled and extension clinical studies worldwide, malignancies occurred more frequently in MAVENCLAD-treated patients (10 events in 3,754 patient-years [0.27 events per 100 patient-years]), compared to placebo patients (3 events in 2,275 patient-years [0.13 events per 100 patient-years]).1
Malignancy rates were higher in US clinical study patients than the rest of the world (4 events in 189 patient-years [2.21 events per 100 patient-years], compared to 0 events in US placebo patients). However, the US results were based on a limited amount of patient data.1
The occurrence of malignancies over time was further assessed.8 This analysis showed no additional increase over time in the adjusted malignancy incidence rate for MAVENCLAD for years 1 to 4 and years 5 to 8+.3*
The analysis is based on a cohort of patients who were treated with MAVENCLAD over 2 years and followed without further dosing. The results of years 5 to 8+ are not dispositive and should be treated with caution. An observational study to assess the long-term risk of malignancy is being conducted.3,9
MAVENCLAD is a purine antimetabolite that interferes with DNA synthesis and repair.1
In clinical studies, patients who received additional MAVENCLAD treatment within 2 years after the first 2 treatment courses had an increased incidence of malignancy (7 events in 790 patient-years [0.91 events per 100 patient-years] calculated from the start of cladribine treatment in year 3). The risk of malignancy with reinitiating MAVENCLAD more than 2 years after the completion of 2 treatment courses has not been studied.1
MAVENCLAD may cause fetal harm when administered to pregnant women. MAVENCLAD is contraindicated for use in pregnant women and in women and men of reproductive potential who do not plan to use effective contraception.
In females of reproductive potential, pregnancy should be excluded before the initiation of each treatment course of MAVENCLAD and prevented by the use of effective contraception during MAVENCLAD dosing and for at least 6 months after the last dose of each treatment course. Women who become pregnant during treatment with MAVENCLAD should discontinue treatment.
EMD Serono has established a surveillance program to analyze pregnancy and infant outcomes in women exposed to MAVENCLAD. To report a pregnancy occurring during treatment with MAVENCLAD or within 6 months after the last tablet taken, in either female patients or the partners of male patients, please visit www.cladribinetabletsinfo.com.
There are no adequate data on the developmental risk associated with use of MAVENCLAD in pregnant women.
In preclinical studies:
No new safety signals have been reported in the 56,000+ patients treated worldwide with MAVENCLAD
WARNING: MALIGNANCIES and RISK OF TERATOGENICITY
CONTRAINDICATIONS
WARNINGS AND PRECAUTIONS
Adverse Reactions: The most common adverse reactions with an incidence of >20% for MAVENCLAD are upper respiratory tract infection, headache, and lymphopenia.
Drug Interactions/Concomitant Medication: Concomitant use of MAVENCLAD with immunosuppressive or myelosuppressive drugs and some immunomodulatory drugs (e.g., interferon beta) is not recommended and may increase the risk of adverse reactions. Acute short-term therapy with corticosteroids can be administered.
Avoid concomitant use of certain antiviral and antiretroviral drugs. Avoid concomitant use of BCRP or ENT/CNT inhibitors as they may alter bioavailability of MAVENCLAD.
Use in Specific Populations: Studies have not been performed in pediatric or elderly patients, pregnant or breastfeeding women. Use in patients with moderate to severe renal or hepatic impairment is not recommended.
Please see the full Prescribing Information, including boxed WARNING for additional information.
MAVENCLAD® (cladribine) tablets is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include relapsing-remitting disease and active secondary progressive disease, in adults. Because of its safety profile, use of MAVENCLAD 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.
Limitations of Use: MAVENCLAD is not recommended for use in patients with clinically isolated syndrome (CIS) because of its safety profile.
WARNING: MALIGNANCIES and RISK OF TERATOGENICITY
CONTRAINDICATIONS
WARNINGS AND PRECAUTIONS
Adverse Reactions: The most common adverse reactions with an incidence of >20% for MAVENCLAD are upper respiratory tract infection, headache, and lymphopenia.
Drug Interactions/Concomitant Medication: Concomitant use of MAVENCLAD with immunosuppressive or myelosuppressive drugs and some immunomodulatory drugs (e.g., interferon beta) is not recommended and may increase the risk of adverse reactions. Acute short-term therapy with corticosteroids can be administered.
Avoid concomitant use of certain antiviral and antiretroviral drugs. Avoid concomitant use of BCRP or ENT/CNT inhibitors as they may alter bioavailability of MAVENCLAD.
Use in Specific Populations: Studies have not been performed in pediatric or elderly patients, pregnant or breastfeeding women. Use in patients with moderate to severe renal or hepatic impairment is not recommended.
Please see the full Prescribing Information, including boxed WARNING for additional information.
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