Mavenclad

Cladribine

THERAPY

Coverage

Protocols

Contraindicated in patients who are:

Hypersensitive to cladribine or to any ingredient in the formulation o component of the container.
Patients with increased risk for opportunistic infections, including those who are immunocompromised due to treatment (e.g. immunosuppressive or immunomodulating therapies, antineoplastic, myelosuppressive therapies, total lymphoid irradiation or bone marrow transplantation) or disease (e.g.immunodeficiency syndrome).
Patients with latent or active infections including active chronic bacterial, fungal or viralinfections (e.g. hepatitis, tuberculosis). Patients with a history of progressive multifocal leukoencephalopathy (PML).
Patients with active malignancy.
Patients with moderate or severe renal impairment (creatinine clearance < 60 mL/min)
Patients who are pregnant or breast-feeding. Women and men of reproductive potential who do not plan to use effective contraception during dosing and for 6 months after last dose in each treatment course.

Before Initiation of Therapy :

CBC,AST,ALT,total bilirubin alkaline phosphatase (month 3,9,12 post treatment or more frequently if lymphocytes fall below 0.5 or liver enzymes start to rise)
Lymphocyte must have recovered ≥0.8 and liver enzymes remained normal before retreating
Annual cerebral MRI
Infections should be assessed and treated promptly.
Blood products need to be irradiated prior to transfusion in order to prevent graft versus host disease

Discontinue Therapy :

Serious opportunistic infection, onset of pregnancy, de novo cancer, recurrant serious infections, evidence of liver injury, persistent grade 3 lymphopenia or pancytopenia

Studies

(Some studies only include abstracts)

Title

Clarity

Source

Date Published

1/12/2011

Clarity extension

1/23/2018

Product Monograph

Specific Concerns

Carcinogenesis:

The incidence of cancer during the original two year study with a cumulative dose of 3.5mg/kg was 0.76% versus 0% in the placebo arm. The drug is known to be genotoxic and clastogenic. The risk-benefit equation in patients with increased baseline risk of cancer should reassessed.

Teratogenicity:

Cladribine causes damage to DNA. Animal studies confirmed its teratogenicity. It should not be prescribed in patients of child bearing potential who cannot or will not use effective contraception for at least 1.5 -2 years following treatment onset. Consideration should be given to the fact that cladribine is a small molecule that penetrates ovarian tissue and affect sperm production.

LIver Damage:

Cases of liver injury usually within 8 weeks of the first cycle have been reported. Liver enzymes monitoring is recommended. Patients with baseline liver injury should not be treated with cladribine.

Infection:

Fatal cases of serious infection such as TB reactivation have been reported. An increased incidence of Zoster has been noted during the trials. VZV vaccination is therefore recommended prior to treatment initiation. The risk of infection during the trials was correlated to the degree of lymphopenia, cumulative dose of cladribine and increased by the addition of interferon beta. Patients with significant baseline immunosuppression from all causes should not be treated with cladribine.