Products
Cladribine was approved for the treatment of multiple sclerosis in the EU in 2017 and in the United States and many countries in 2019 in tablet form (Mavenclad). Cladribine has also been commercially available as an infusion and injection solution in many countries since 1998 (Litak). This article relates to MS therapy.
Structure and properties
Cladribine (C10H12ClN5O3, Mr = 285.7 g/mol) is a 2-chloro derivative of 2′-deoxyadenosine. Chlorination protects the nucleoside analog from metabolic degradation. Cladribine exists as a white, non-hygroscopic and crystalline powder.
Effects
Cladribine (ATC L01BB04) has selective cytotoxic, proapoptotic, and immunomodulatory properties. It is a prodrug that is phosphorylated in cells to the active triphosphate Cd-ATP. This activation occurs mainly in lymphocytes (B and T cells), whose numbers are reduced as a result. B and T cells are significantly involved in the development of multiple sclerosis. The selective reduction leads to a significant decrease in the relapse rate. The effects are based on integration into DNA, which inhibits DNA synthesis and induces apoptosis. Cladribine competes with deoxyadenosine triphosphate, among others, for incorporation into DNA by DNA polymerases. The drug has a half-life of approximately 24 hours.
Indications
For the treatment of adult patients with highly active relapsing-remitting multiple sclerosis (MS) defined by clinical or imaging findings.
Dosage
According to the SmPC. Therapy consists of two treatment phases spanning two consecutive years. Each treatment phase consists of two treatment weeks, one at the beginning of the first month and one at the beginning of the second month of each treatment year. Each treatment week consists of 4 or 5 days during which the patient receives the tablets as a single daily dose. Other medicines should be taken at a time interval of at least three hours. The intake is independent of meals. After completion of the two treatment phases, no further treatment with cladribine is required in years 3 and 4. Resumption of therapy after year 4 has not been studied. For detailed instructions, please refer to the SmPC!
Contraindications
- Hypersensitivity
- Infection with the HI virus
- Severe active infections, active chronic infection (eg, tuberculosis or hepatitis).
- Initiation of treatment in immunocompromised patients, including patients currently receiving immunosuppressive or myelosuppressive therapy.
- Existing active malignancies.
- History of progressive multifocal leukencephalopathy.
- Moderate or severe renal function impairment.
- Children and adolescents under 18 years
- Pregnancy and lactation
Full precautions can be found in the drug label.
Adverse effects
The most common possible adverse effects include lymphopenia, decrease in neutrophil count, oral herpes, dermatomal herpes zoster, rash, and hair loss.
