accines at least 4 to 6 weeks prior to startingMAVENCLAD, because of a risk of active vaccine infection (see Herpes Virus Infections).
Avoid vaccination with live-attenuated or live vaccines during and after MAVENCLADtreatment while the patient’s white blood cell counts are not within normal limits.
5.5 Hematologic Toxicity
In addition to lymphopenia [see Warnings and Precautions (5.3)], decreases in other blood cellsand hematological parameters have been reported with MAVENCLAD in clinical studies. Mildto moderate decreases in neutrophil counts (cell count between 1,000 cells per microliter and< lower limit of normal (LLN)) were observed in 27% of MAVENCLAD-treated patients,compared to 13% of placebo patients whereas severe decreases in neutrophil counts (cell countbelow 1,000 cells per microliter) were observed in 3.6% of MAVENCLAD-treated patients,compared to 2.8% of placebo patients. Decreases in hemoglobin levels, in general mild tomoderate (hemoglobin 8.0 g per dL to < LLN), were observed in 26% of MAVENCLAD-treatedpatients, compared to 19% of placebo patients. Decreases in platelet counts were generally mild
(cell count 75,000 cells per microliter to < LLN) and were observed in 11% of MAVENCLADtreatedpatients, compared to 4% of placebo patients.
In clinical studies at dosages similar to or higher than the approved MAVENCLAD dosage,serious cases of thrombocytopenia, neutropenia, and pancytopenia (some with documented bonemarrow hypoplasia) requiring transfusion and granulocyte-colony stimulating factor treatmenthave been reported [see Warnings and Precautions (5.6) for information regarding graft-versushostdisease with blood transfusion].
Obtain complete blood count (CBC) with differential prior to, during, and after treatment with
MAVENCLAD [see Dosage and Administration (2.1, 2.5)].
5.6 Graft-Versus-Host Disease With Blood Transfusion
Transfusion-associated graft-versus-host disease has been observed rarely after transfusion ofnonirradiated blood in patients treated with cladribine for non-MS treatment indications.
In patients who require blood transfusion, irradiation of cellular blood components isrecommended prior to administration to decrease the risk of transfusion-related graft-versus-hostdisease. Consultation with a hematologist is advised.
5.7 Liver Injury
In clinical studies, 0.3% of MAVENCLAD-treated patients had liver injury (serious or causingtreatment discontinuation) considered related to treatment, compared to 0 placebo patients.
Onsethas ranged from a few weeks to several months after initiation of treatment with MAVENCLAD.
Signs and symptoms of liver injury, including elevation of serum aminotransferases to greaterthan 20-fold the upper limit of normal, have been observed. These abnormalities resolved upontreatment discontinuation.
Obtain serum aminotransferase, alkaline phosphatase, and total bilirubin levels prior to the firstand second treatment course [see Dosage and Administration (2.1)]. If a patient develops clinicalsigns, including unexplained liver enzyme elevations or symptoms suggestive of hepaticdysfunction (e.g., unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundiceand/or dark urine), promptly measure serum transaminases and total bilirubin and interrupt ordiscontinue treatment with MAVENCLAD, as appropriate.
5.8 Hypersensitivity
In clinical studies, 11% of MAVENCLAD-treat |
