gram developed tuberculosis.
All three cases occurred in regions where tuberculosis is endemic. One case of tuberculosis wasfatal, and two cases resolved with treatment.
Perform tuberculosis screening prior to initiation of the first and second treatment course ofMAVENCLAD. Latent tuberculosis infections may be activated with use of MAVENCLAD.
Inpatients with tuberculosis infection, delay initiation of MAVENCLAD until the infection hasbeen adequately treated.
Hepatitis
One clinical study patient died from fulminant hepatitis B infection. Perform screening forhepatitis B and C prior to initiation of the first and second treatment course of MAVENCLAD.
Latent hepatitis infections may be activated with use of MAVENCLAD. Patients who arecarriers of hepatitis B or C virus may be at risk of irreversible liver damage caused by virusreactivation. In patients with hepatitis infection, delay initiation of MAVENCLAD until theinfection has been adequately treated.
Herpes Virus Infections
In controlled clinical studies, 6% of MAVENCLAD-treated patients developed a herpes viralinfection compared to 2% of placebo patients. The most frequent types of herpes viral infectionswere herpes zoster infections (2.0% vs. 0.2%) and oral herpes (2.6% vs. 1.2%). Serious herpeszoster infections occurred in 0.2% of MAVENCLAD-treated patients.
Vaccination of patients who are antibody-negative for varicella zoster virus is recommendedprior to initiation of MAVENCLAD. Administer live-attenuated or live vaccines at least 4 to6 weeks prior to starting MAVENCLAD.
The incidence of herpes zoster was higher during the period of absolute lymphocyte count lessthan 500 cells per microliter, compared to the time when the patients were not experiencing thisdegree of lymphopenia. Administer anti-herpes prophylaxis in patients with lymphocyte countsless than 200 cells per microliter.
Patients with lymphocyte counts below 500 cells per microliter should be monitored for signsand symptoms suggestive of infections, including herpes infections. If such signs and symptomsoccur, initiate treatment as clinically indicated. Consider interruption or delay of MAVENCLADuntil resolution of the infection.
Progressive Multifocal Leukoencephalopathy
Progressive multifocal leukoencephalopathy (PML) is an opportunistic viral infection of thebrain caused by the JC virus (JCV) that typically only occurs in patients who areimmunocompromised, and that usually leads to death or severe disability. Typical symptomsassociated with PML are diverse, progress over days to weeks, and include progressive weaknesson one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking,memory, and orientation leading to confusion and personality changes.
No case of PML has been reported in clinical studies of cladribine in patients with multiplesclerosis. In patients treated with parenteral cladribine for oncologic indications, cases of PMLhave been reported in the postmarketing setting.
Obtain a baseline (within 3 months) magnetic resonance imaging (MRI) before initiating the firsttreatment course of MAVENCLAD. At the first sign or symptom suggestive of PML, withholdMAVENCLAD and perform an appropriate diagnostic eva luation. MRI findings may beapparent before clinical signs or symptoms.
Vaccinations
Administer all immunizations according to immunization guidelines prior to startingMAVENCLAD. Administer live-attenuated or live v |
