of Teratogenicity
MAVENCLAD may cause fetal harm when administered to pregnant women. Malformationsand embryolethality occurred in animals [see Use in Specific Populations (8.1)]. Advise womenof the potential risk to a fetus during MAVENCLAD dosing and for 6 months after the last dosein each treatment course.
In females of reproductive potential, pregnancy should be excluded before initiation of eachtreatment course of MAVENCLAD and prevented by the use of effective contraception duringMAVENCLAD dosing and for at least 6 months after the last dose of each treatment course.
Women who become pregnant during treatment with MAVENCLAD should discontinuetreatment [see Use in Specific Populations (8.1, 8.3)].
MAVENCLAD is contraindicated for usein pregnant women and in women and men of reproductive potential who do not plan to useeffective contraception.
5.3 Lymphopenia
MAVENCLAD causes a dose-dependent reduction in lymphocyte count. In clinical studies, 87%of MAVENCLAD-treated patients experienced lymphopenia. The lowest absolute lymphocytecounts occurred approximately 2 to 3 months after the start of each treatment course and werelower with each additional treatment course. In patients treated with a cumulative dose of
MAVENCLAD 3.5 mg per kg over 2 courses as monotherapy, 26% and 1% had nadir absolutelymphocyte counts less than 500 and less than 200 cells per microliter, respectively. At the endof the second treatment course, 2% of clinical study patients had lymphocyte counts less than500 cells per microliter; median time to recovery to at least 800 cells per microliter wasapproximately 28 weeks.
Additive hematological adverse reactions may be expected if MAVENCLAD is administeredprior to or concomitantly with other drugs that affect the hematological profile [see DrugInteractions (7.3)].
The incidence of lymphopenia less than 500 cells per microliter was higher inpatients 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%).
Obtain complete blood count (CBC) with differential including lymphocyte count prior to,during, and after treatment with MAVENCLAD. See Dosage and Administration (2.1, 2.5) andWarnings and Precautions (5.4) for timing of CBC measurements and additional instructionsbased on the patient’s lymphocyte counts and clinical status (e.g., infections).
5.4 Infections
MAVENCLAD can reduce the body's immune defense and may increase the likelihood ofinfections. Infections occurred in 49% of MAVENCLAD-treated patients compared to 44% ofplacebo patients in clinical studies. The most frequent serious infections in MAVENCLADtreatedpatients included herpes zoster and pyelonephritis (see Herpes Virus Infections).
Fungalinfections were observed, including cases of coccidioidomycosis.
HIV infection, active tuberculosis, and active hepatitis must be excluded before initiation of eachtreatment course of MAVENCLAD [see Contraindications (4)].
Consider a delay in initiation of MAVENCLAD in patients with an acute infection until theinfection is fully controlled.
Initiation of MAVENCLAD in patients currently receiving immunosuppressive ormyelosuppressive therapy is not recommended [see Drug Interactions (7.1)].
Concomitant useof MAVENCLAD with these therapies could increase the risk of immunosuppression.
Tuberculosis
Three of 1,976 (0.2%) cladribine-treated patients in the clinical pro |
