Dasatinib:Class, Uses, Advantages,Usage and Toxicity

Dasatinib is an orally available multikinase inhibitor indicated for the treatment of Philadelphia chromosome (Ph)-positive leukemias.

Class

Cancer medicine

Mechanism of action

Dasatinib is a type of cancer growth blocker called a tyrosine kinase inhibitor Open a glossary item (TKI). It works by blocking particular proteins on cancer cells that encourage the cancer to grow. This can help shrink the cancer or stop it growing.

Uses

Dasatinib is indicated for the treatment of newly diagnosed adults with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase, as well as adults with chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib, and adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy. Dasatinib is also indicated for the treatment of pediatric patients 1 year of age and older with Ph+ CML in chronic phase or newly diagnosed Ph+ ALL in combination with chemotherapy.

Advantages

Unlike imatinib, another tyrosine kinase used for the treatment of CML and Ph-positive ALL, dasatinib inhibits the active and inactive conformations of the ABL kinase domain. Also, mutations in the kinase domain of BCR-ABL may lead to relapse during imatinib treatment. Since dasatinib does not interact with some of the residues involved in those mutations, the use of this drug represents a therapeutic alternative for patients with cancers that have developed imatinib-resistance. The use of dasatinib was first approved by the FDA in 2006.

Usage

Dasatinib comes as a tablet to take by mouth. It is usually taken once a day, in the morning or in the evening, with or without food. Take dasatinib at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take dasatinib exactly as directed.

Toxicity

Overdose cases with dasatinib occurred in isolated cases during clinical studies. Patients that received 280 mg of dasatinib per day for 1 week developed severe myelosuppression and bleeding. Since dasatinib is associated with severe myelosuppression, patients that ingest more than the recommended dosage should be monitored closely for myelosuppression and receive appropriate supportive treatment.[1]

Acute overdose in animals was associated with cardiotoxicity. In rodents, ventricular necrosis and valvular/ventricular/atrial hemorrhage were detected at single doses higher than or equal to 100 mg/kg (600 mg/m2). In monkeys receiving single doses higher than or equal to 10 mg/kg (120 mg/m2), there was a tendency for increased systolic and diastolic blood pressure. In rats, the oral LD50 of dasatinib is 50-100 mg/kg, and in monkeys, it is 25-45 mg/kg.

References

[1]FDA Approved Drug Products: Sprycel (dasatinib) tablets for oral use (February 2023) .

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