ne values have also been observed in clinical studies, although these parameters usually remain within normal limits.
Additive haematological adverse reactions may be expected if cladribine is administered prior to or concomitantly with other substances that affect the haematological profile (see section 4.5).
Lymphocyte counts must be determined
• before initiating MAVENCLAD in year 1,
• before initiating MAVENCLAD in year 2,
• 2 and 6 months after start of treatment in each treatment year. If the lymphocyte count is below 500 cells/mm3, it should be actively monitored until values increase again.
For treatment decisions based on the patient's lymphocyte counts, see section 4.2 and subsection 'Infections' below.
Infections
Cladribine can reduce the body's immune defence and may increase the likelihood of infections. HIV infection, active tuberculosis and active hepatitis must be excluded before initiation of cladribine (see section 4.3).
Latent infections may be activated, including tuberculosis or hepatitis. Therefore, screening for latent infections, in particular tuberculosis and hepatitis B and C, must be performed prior to initiation of therapy in year 1 and year 2. Initiation of MAVENCLAD should be delayed until the infection has been adequately treated.
A delay in initiation of cladribine should also be considered in patients with an acute infection until the infection is fully controlled.
Particular attention is recommended for patients who have no history of exposure to varicella zoster virus. Vaccination of antibody-negative patients is recommended prior to initiation of cladribine therapy. Initiation of treatment with MAVENCLAD must be postponed for 4 to 6 weeks to allow for the full effect of vaccination to occur.
The incidence of herpes zoster was increased in patients on cladribine. If lymphocyte counts drop below 200 cells/mm3, anti-herpes prophylaxis according to local standard practice should be considered during the time of grade 4 lymphopenia (see section 4.8).
Patients with lymphocyte counts below 500 cells/mm3 should be actively monitored for signs and symptoms suggestive of infections, in particular herpes zoster. If such signs and symptoms occur, anti- infective treatment should be initiated as clinically indicated. Interruption or delay of MAVENCLAD may be considered until proper resolution of the infection.
Cases of progressive multifocal leukoencephalopathy (PML) have been reported for parenteral cladribine in patients treated for hairy cell leukaemia with a different treatment regimen.
In the clinical study data base of cladribine in MS (1,976 patients, 8,650 patient years) no case of PML has been reported. However, a baseline magnetic resonance imaging (MRI) should be performed before initiating MAVENCLAD (usually within 3 months).
Malignancies
In clinical studies, events of malignancies were observed more frequently in cladribine-treated patients compared to patients who received placebo (see section 4.8).
MAVENCLAD is contraindicated in MS patients with active malignancies (see section 4.3). An individual benefit-risk eva luation should be performed before initiating MAVENCLAD in patients with prior malignancy. Patients treated with MAVENCLAD should be advised to follow standard cancer screening guidelines.
Contraception
Before initiation of treatment both in year 1 and year 2, women of childbearing potential and males who could poten |
