Cladribine

Cladribine is a purine analog or chlorinated derivative of adenine that causes apoptosis in B and T cells. Cladribine was first approved in the United States in 1993 as a treatment for a variety of hematological malignancies; it is now approved to treat hairy cell leukemia. 

BRAND NAME:

Litak ® - Litak ® is available in the form of an injection that contains cladribine 2mg/ml as an active substance that helps in treating the rare forms of leukemia or lymphoma.

Mavenclad – It is an oral tablet that contains cladribine as an active ingredient.

MECHANISM OF ACTION:

Cladribine is a purine nucleoside analog, it is a prodrug that is activated by phosphorylation and converted into the active moiety, Cd-ATP. This active form incorporates into DNA to result in the breakage of DNA strand and shutdown of DNA synthesis and repair. This also results in a depletion of Nicotinamide adenine dinucleotide and adenosine triphosphate. Cladribine is cell-cycle nonspecific. The mechanism of cladribine in treating multiple sclerosis is unknown but involves cytotoxic effects on B and T lymphocytes that result from the shutdown of DNA synthesis, leading to a depletion of lymphocytes.

PHARMACOKINETICS:

Absorption: Cladribine has a biological availability of about 40%. Cladribine administered quickly resulted in a median time to a maximum concentration of 0.5 hours. Following administration of cladribine with a high-fat meal, the geometric mean Cmax dropped by 29% but the AU remained constant. The Tmax was increased to 1.5 hours.

Distribution: The 20% of cladribine binds with the plasma protein and is independent of plasma concentration in vitro. Intracellular cladribine concentration in human lymphocytes was approximately 30 to 40 times extracellular, in vitro.

Metabolism: Cladribine is a prodrug phosphorylated to the active moiety Cd-AMP by deoxycytidine kinase in lymphocytes. Cd-AMP is further phosphorylated, yielding cladribine diphosphate and Cd-ATP. Cytoplasmic 5'-NTase catalyzes the dephosphorylation and inactivation of. The metabolism of cladribine in the blood has not been extensively studied. However, significant whole blood and little hepatic enzyme metabolism were seen in vitro.

Excretion: Cladribine's terminal half-life is approximately 24 hours. The intracellular half-life of the cladribine phosphorylated metabolite cladribine monophosphate is 15 hours, while Cd-ATP is 10 hours. It is estimated that the median apparent renal clearance is 22.2 L/hr, while nonrenal clearance is 23.4 L/hr.

PHARMACODYNAMICS:

Cladribine may have mutual additive or synergistic effects on the immune system. Tablets are used in conjunction with immunosuppressive or myelosuppressive medications. In a similar vein, using Cladribine Tablets concurrently with drugs that alter the hematological profile, like carbamazepine, increases the likelihood of a hematological adverse response.

DOSAGE AND ADMINISTRATION:

Cladribine is an orally given medication. A medication is provided in 10-mg pills that should not be crushed or eaten. The recommended dosage for an adult with an average body weight is 10 to 20 mg per day for four to five days, as instructed by a physician.

CONTRAINDICATIONS:

Individuals with hepatic cirrhosis, chronic kidney illness, active cancer, HIV, or tuberculosis should not use cladribine if they have multiple sclerosis.

A history of using other immune suppressants, such as cyclophosphamide, azathioprine, methotrexate, or mitoxantrone, is another reason not to use cladribine. Cladribine demonstrates the impact on the viability and quality of sperm.

DRUG INTERACTIONS:

Certain cladribine-interacting products have the potential to exacerbate immune system weakness and make infections more likely.

SIDE EFFECTS:

• Nausea and vomiting.

• Dizziness

• Headache

• Cough

• Diarrhea

• stomach pain

• Constipation

• Pain or swelling around the injection site.

OVER DOSE:

Overdose symptoms may include weakness/numbness/tingling in the hands/feet, inability to move arms/legs, changes in urine volume, and signs of illness such as sore throat, fever, unusual weariness, and a fast heartbeat.

TOXICITY:

High doses of Cladribine have been linked to irreversible neurologic damage, acute nephrotoxicity, and severe bone marrow suppression, which causes neutropenia, anemia, and thrombocytopenia. Lymphopenia may also occur, which is dosage-dependent. There is no known antidote for cladribine overdose; hence, treatment comprises drug cessation, careful monitoring, and appropriate supporting measures. Although it is unknown whether cladribine can be eliminated from the bloodstream using dialysis or hemofiltration due to its quick and wide intracellular and tissue distribution, hemodialysis is unlikely to significantly reduce cladribine levels.

STORAGE:

Keep the item in its original packing to avoid moisture damage. Maintain storage between 20°C and 25°C (68°F and 77°F); temperature variations are allowed between 15°C and 30°C.