Active ingredient: Cladribine - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Immunosuppressive Agents
• Antineoplastic Agents

Dosage Forms

• Solution

Brands / Synonyms

-deoxy-beta-adenosine; -deoxyadenosine; 2-CdA; 2-Chloro-2' 2-Chlorodeoxyadenosine; Chlorodeoxyadenosine; Cladribine [USAN:BAN:INN]; Leustatin; Leustatin

Indications

For the treatment of active hairy cell leukemia (leukemic reticuloendotheliosis) as defined by clinically significant anemia, neutropenia, thrombocytopenia, or disease-related symptoms.

Pharmacology

Cladribine is a synthetic antineoplastic agent with immunosuppressive effects. Cladribine is one of a group of chemotherapy drugs known as the anti-metabolites. Anti-metabolites stop cells making and repairing DNA. Cancer cells need to make and repair DNA in order to grow and multiply.

Mechanism of Action

Cladribine is structurally related to fludarabine and pentostatin but has a different mechanism of action. It is phosphorylated to its corresponding nucleotide CdATP, which accumulates and is incorporated into the DNA of cells such as lymphocytes. High levels of CdATP lead to DNA strand breaks, inhibition of DNA synthesis, and cell death. Unlike other antimetabolite drugs, cladribine has cytotoxic effects on resting as well as proliferating lymphocytes. However, it does cause cells to accumulate at the G1/S phase junction, suggesting that cytotoxicity is associated with events critical to cell entry into S phase. It also binds purine nucleoside phosphorylase (PNP), however no relationship between this binding and a mechanism of action has been established.

Absorption

Oral bioavailability is 34 to 48%.

Toxicity

Symptoms of overdose include irreversible neurologic toxicity (paraparesis/quadriparesis), acute nephrotoxicity, and severe bone marrow suppression resulting in neutropenia, anemia and thrombocytopenia.

Biotrnasformation / Drug Metabolism

Metabolized in all cells with deoxycytidine kinase activity to 2-chloro-2'-deoxyadenosine-5'-triphosphate

Contraindications

LEUSTATIN^® (cladribine) Injection is contraindicated in those patients who are hypersensitive to this drug or any of its components.

Drug Interactions

There are no known drug interactions with LEUSTATIN Injection. Caution should be exercised if LEUSTATIN Injection is administered before, after, or in conjunction with other drugs known to cause immunosuppression or myelosuppression.