Dasatinib Anhydrous is an orally bioavailable synthetic small molecule-inhibitor of SRC-family protein-tyrosine kinases. Dasatinib binds to and inhibits the growth-promoting activities of these kinases. Apparently, because of its less stringent binding affinity for the BCR-ABL kinase, dasatinib has been shown to overcome the resistance to imatinib of chronic myeloid leukemia (CML) cells harboring BCR-ABL kinase domain point mutations. SRC-family protein-tyrosine kinases interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways; tumorigenic forms can occur through altered regulation or expression of the endogenous protein and by way of virally-encoded kinase genes.
Dasatinib is a chemotherapy medication used to treat certain cases of chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL). Dasatinib belongs to the class of medications called protein-tyrosine kinase inhibitors Specifically it is used to treat cases that are Philadelphia chromosome-positive (Ph+). It is taken by mouth. Dasatinib is an oral dual BCR/ABL and Src family tyrosine kinase inhibitor approved for use in patients with chronic myelogenous leukemia (CML). The main targets of Dasatinib, are BCR-ABL, SRC, Ephrins and GFR.
Mechanism of Action of Dasatinib
Dasatinib, at nanomolar concentrations, inhibits the following kinases: BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ. Based on modeling studies, dasatinib is predicted to bind to multiple conformations of the ABL kinase. In vitro, dasatinib was active in leukemic cell lines representing variants of imatinib mesylate sensitive and resistant disease. Dasatinib inhibited the growth of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines overexpressing BCR-ABL. Under the conditions of the assays, dasatinib was able to overcome imatinib resistance resulting from BCR-ABL kinase domain mutations, activation of alternate signaling pathways involving the SRC family kinases (LYN, HCK), and multi-drug resistance gene overexpression.
Indications of Dasatinib
- Acute lymphoblastic leukemia
- Chronic myelogenous leukemia
- Acute lymphoblastic leukaemias
- Chronic myeloid leukemia
- Newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukaemia (CML) in the chronic phase.
- Chronic, accelerated or blast phase CML with resistance or intolerance to prior therapy including imatinib mesilate.
- Ph+ acute lymphoblastic leukaemia (ALL) and lymphoid blast CML with resistance or intolerance to prior therapy.
- Dasatinib is also used to treat people with chronic myeloid leukemia and people with acute lymphoblastic leukemia who are positive for the Philadelphia chromosome.
- For the treatment of adults with chronic, accelerated, or myeloid or lymphoid blast phase chronic myeloid leukemia with resistance or intolerance to prior therapy. Also indicated for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia with resistance or intolerance to prior therapy.
Contra Indications of Dasatinib
- Anemia, bone marrow suppression, neutropenia, thrombocytopenia. …
- Anticoagulant therapy, bleeding, GI bleeding, intracranial bleeding. …
- Edema, pericardial effusion, pleural effusion.
Dosage of Dasatinib
Strengths: 70 mg; 20 mg; 50 mg; 100 mg; 80 mg; 140 mg
Chronic Phase CML
- 100 mg orally once a day
Accelerated Phase CML, Myeloid or Lymphoid Blast Phase CML, Ph+ ALL
- 140 mg orally once a day
Side Effects of Dasatinib
The most common
- chest pain
- certainly hair loss
- joint painPain
- nausea and vomiting
- Severe stomach ache
- epigastric pain,
- fainting, fast or pounding heartbeats.
- Fast or irregular heartbeat
- appetite loss
- changes in nails
- Back pain
- increased cough
- Acid or sour stomach
- decreased appetite
- chest congestion
- chest pain
- cold sweats
- decreased sexual ability or desire
- stomach or abdominal cramps, gas, or pain
- trouble sleeping
- bleeding gums
- blood in the urine or stools
- chest pain
- Burning, crawling, itching, numbness, prickling, “pins and needles“, or tingling feelings
- difficulty in moving
- muscle stiffness
- redness of the face, neck, arms and occasionally, upper chest
- lack or loss of strength
- muscle spasm
- difficult or labored breathing
- dry mouth
- lack or loss of strength
- loose stools
- loss of interest or pleasure
- muscle stiffness
- night sweats
- passing gas
- stomach discomfort, upset, or pain
- swollen joints
- trouble concentrating
- increased blood pressure
Drug Interactions of Dasatinib
Dasatinib may interact with following drugs, supplyments & may change the efficacy of drugs
- alpha blockers (e.g., alfuzosin, doxazosin, silodosin, tamsulosin)
- anticancer medications (e.g., cabazitaxel, docetaxel, doxorubicin, etoposide, ifosfamide, irinotecan, vincristine)
- “azole” antifungal medications (e.g., fluconazole, itraconazole, ketoconazole)
- beta-blockers (e.g., atenolol, propranolol, metoprolol)
- barbiturates (e.g., butalbital, pentobarbital, phenobarbital)
- benzodiazepines (e.g., chlordiazepoxide, clonazepam, diazepam, lorazepam)
- calcium channel blockers (e.g., nifedipine, diltiazem, verapamil, amlodipine, )
- corticosteroids (e.g., dexamethasone, prednisone, methylprednisolone)
- “gliptin” diabetes medications (e.g., linagliptin, saxagliptin, sitagliptin)
- HIV protease inhibitors (e.g., atazanavir, indinavir, ritonavir, saquinavir)
- macrolide antibiotics (e.g., azithromycin, clarithromycin, erythromycin)
- progestins (e.g., dienogest, levonorgestrel, medroxyprogesterone, norethindrone)
- proton pump inhibitors (PPIs;e.g., esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole)
- selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine,paroxetine, sertraline)
- “statin” anticholesterol medications (e.g., atorvastatin, lovastatin, simvastatin)
- other selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, fluoxetine, sertraline)
- 5-HT3 antagonists (e.g., granisetron, ondansetron)
- thiazide diuretics (e.g., hydrochlorothiazide, indapamide)
- tricyclic antidepressants (e.g., nortriptyline, amitriptyline, imipramine,
- other tyrosine kinase inhibitors (e.g., dasatinib, imatinib, nilotinib, sunitinib)
FDA Pregnancy Category D
This medication should not be used during pregnancy or by women who are planning to become pregnant. If it is taken by a woman who is pregnant, it may harm the developing baby. Women should avoid becoming pregnant while taking dasatinib. If you become pregnant while taking this medication, contact your doctor immediately.
It is not known if dasatinib passes into breast milk. Due to the potential for serious harm to a baby, if they are exposed to this medication, breast-feeding must be stopped before starting this medication. The safety and effectiveness of using this medication have not been established for children less than 18 years of age.