TYKODAS 50 MG

Indications

• Chronic Myeloid Leukemia (CML)
• Acute Lymphoblastic Leukemia (ALL)

Dosage

Children: Refer to BNF for Children for specific dosing information.

Adults: 140 mg once daily, with the possibility of increasing the dose to 180 mg once daily if necessary.

Mechanism of action

Dasatinib is a multikinase inhibitor that targets several tyrosine kinases, including BCR-ABL, SRC family kinases (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ. It binds with higher affinity to both the active and inactive conformations of the ABL kinase domain compared to imatinib, effectively inhibiting cell growth in leukemia cell lines and overcoming resistance associated with certain BCR-ABL mutations.

Pharmacodynamics

Dasatinib is an orally available small-molecule that exhibits myelosuppressive effects and has been associated with various adverse reactions, including QTc prolongation, fluid retention, bleeding events, and hepatotoxicity. During clinical trials, adverse reactions were relatively uncommon, with less than 1% of patients experiencing significant QTc prolongation. Dasatinib also carries risks of embryo-fetal toxicity, particularly in pediatric patients, potentially impacting bone growth and development.

Pharmacokinetics

Dasatinib is absorbed after oral administration, and its pharmacokinetics can be influenced by food and other drugs. The drug is primarily metabolized by the liver, and caution is advised in patients with hepatic impairment. The elimination half-life is approximately 3 to 5 hours, with renal excretion of metabolites. Regular monitoring of liver function is recommended due to the risk of hepatotoxicity.

Contra-indications

• Severe hepatic impairment
• Active hepatitis B infection
• Pregnancy

Adverse effects

• Alopecia
• Anaemia
• Appetite abnormal
• Arrhythmias
• Arthralgia
• Asthenia
• Bone disorders
• Cardiac dysfunction
• Cardiomyopathy
• Chest pain
• Constipation
• Cough
• Depression
• Diarrhoea
• Dizziness
• Drowsiness
• Dry eye
• Dyspnoea
• Eye inflammation
• Facial swelling
• Fever
• Fluid imbalance
• Flushing
• Gastrointestinal discomfort
• Gastrointestinal disorders
• Genital abnormalities
• Growth retardation
• Haemorrhage
• Headache
• Pulmonary arterial hypertension
• Tumor lysis syndrome
• Hepatotoxicity

Interactions

• Grapefruit juice - Severe increase in exposure
• Mitotane - Severe decrease in exposure
• Rifampicin - Severe decrease in exposure
• Belzutifan - Moderate decrease in exposure
• Cenobamate - Moderate decrease in exposure
• Cobicistat - Moderate increase in exposure
• Idelalisib - Moderate increase in exposure
• Dronedarone - Unknown increase in exposure
• Antifungal azoles - Unknown increase in exposure
• Crizotinib - Unknown increase in exposure

Precautions

• Monitor liver function periodically
• Caution in patients with cardiac dysfunction
• Monitor for signs of QT interval prolongation
• Use effective contraception during treatment and for at least 17 days after stopping treatment
• Patients should wear protective clothing and apply sunscreen before sun exposure

Pregnancy

Manufacturer advises to avoid use during pregnancy due to potential risks.

Breast-feeding

Manufacturer advises to avoid use during breastfeeding; no information available.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Dasatinib 100 mg film-coated

Mechanism of action

Dasatinib is a tyrosine kinase inhibitor with several targets. At nanomolar concentrations, it inhibits BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ. In patients with chronic myeloid leukemia (CML), the tyrosine kinase activity of BCR-ABL is deregulated, leading to the growth, proliferation and survival of cancerous hematopoietic cells. Dasatinib binds to the active and inactive conformation of the ABL kinase domain with a higher affinity than imatinib. In chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines overexpressing BCR-ABL, dasatinib inhibits cell growth. Also, dasatinib has _in vitro_ activity against leukemic cell lines that are either sensitive or resistant to imatinib. It has been suggested that dasatinib is able to overcome imatinib resistance caused by BCR-ABL kinase domain mutations because it does not require interaction with some of the residues involved in those mutations.

Pharmacodynamics

Dasatinib is an orally available small-molecule multikinase inhibitor. During clinical trials, less than 1% of patients treated with dasatinib had QTc prolongation as an adverse reaction, and 1% experienced a QTcF higher than 500 ms. The use of dasatinib is also associated with myelosuppression, bleeding-related events, fluid retention, cardiovascular toxicity, pulmonary arterial hypertension, severe dermatologic reactions, tumor lysis syndrome and hepatotoxicity. It may also cause embryo-fetal toxicity and lead to adverse reactions associated with bone growth and development in pediatric patients.