Dasatinib

Indications

Dasatinib is used for: Chronic myeloid leukaemia

Adult Dose

Oral Chronic myeloid leukaemia Adult: Chronic phase CML: Initially, 100 mg once daily, may increase up to 140 mg once daily. Accelerated, myeloid or lymphoid blast phase CML or Philadelphia chromosome-positive ALL: Initially, 140 mg once daily, may increase up to 180 mg once daily. Hepatic impairment: No dosage adjustment needed.

Child Dose

Renal Dose

Administration

May be taken with or without food. Swallow whole, do not break/crush/cut.

Contra Indications

Concomitant use w/ CYP3A4 inhibitors (e.g. atazanavir, clarithromycin, erythromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole or grapefruit juice); CYP3A4 inducers (e.g. carbamazepine, dexamethasone, phenytoin, phenobarbital, rifampicin or St John's wort); antacid. Pregnancy.

Precautions

Patients w/ predisposing factors for QT prolongation (e.g. congenital long QT syndrome, hypokalaemia, hypomagnesaemia, on antiarrhythmic therapy, or receiving cumulative high doses of anthracyclines). Hepatic impairment. Lactation. Monitoring Parameters Evaluate patients for manifestations of underlying cardiopulmonary disease prior to and during therapy. Measure full blood counts wkly for the 1st 2 mth and then mthly thereafter. Lactation: not known if excreted in breast milk; do not nurse

Pregnancy-Lactation

Pregnancy Based on limited human data, dasatinib can cause fetal harm when administered to a pregnant woman; adverse pharmacologic effects (eg, hydrops fetalis, fetal leukopenia, and fetal thrombocytopenia) have been reported with maternal exposure to dasatinib Animal reproduction studies in rats have demonstrated extensive mortality during organogenesis, the fetal period, and in neonates; skeletal malformations were observed in a limited number of surviving rat and rabbit conceptuses; these findings occurred at dasatinib plasma concentrations below those in humans receiving therapeutic doses of dasatinib Advise a pregnant woman of the potential risk to a fetus Transplacental transfer of dasatinib has been reported Advise females of reproductive potential to avoid pregnancy, which may include the use of effective contraceptive methods, during treatment with dasatinib and for 30 days after the final dose Based on animal data, dasatinib may result in damage to female and male reproductive tissues Lactation No data are available regarding the presence of dasatinib in human milk, the effects of the drug on the breastfed child, or the effects of the drug on milk production However, dasatinib is present in the milk of lactating rats

Interactions

Concomitant use w/ drugs that have narrow therapeutic index (e.g. alfentanil, cisapride, ciclosporin, fentanyl, pimozide, quinidine, simvastatin, sirolimus, tacrolimus, ergot alkaloids) as it may increase the serum levels of these drugs. Increased risk of bleeding and thrombocytopenia w/ antiplatelet drugs, anticoagulants, and NSAIDs. Potentially Fatal: May reduce plasma levels w/ antacids, administer antacid 2 hr apart from the admin of dasatinib. May increase plasma levels w/ CYP3A4 inhibitors (e.g. atazanavir, clarithromycin, erythromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin or voriconazole). May reduce plasma levels w/ CYP3A4 inducers (e.g. carbamazepine, dexamethasone, phenytoin, phenobarbital or rifampicin).

Adverse Effects

Side effects of Dasatinib : >10% Fluid retention, incl CHF, pulm edema, pleural effusion (50%), Diarrhea (49%), Headache (40%), Hemorrhage (40%), Fatigue (39%), Pyrexia (39%), Skin rash (35%), Infection (34%), Nausea (34%), Dyspnea (32%), Cough (28%), Pain (26%), Abdominal pain (25%), Vomiting (22%), Anorexia (19%), Arthralgia (19%), Asthenia (19%), Constipation (14%), Dizziness (14%), Musculoskeletal pain (14%), Weight loss (14%), Chest pain (13%), Neuropathy (13%), Myalgia (12%), Abdominal distention (11%), Arrhythmia (11%), Chills (11%), Pneumonia (11%), Pruritus (11%), Weight gain (11%) 1-10% (selected) Anemia, Febrile neutropenia, Thrombocytopenia, Mucosal inflammation Vascular disorders: Thrombosis/embolism (including pulmonary embolism, deep vein thrombosis) Respiratory, thoracic, and mediastinal disorders: Interstitial lung disease, pulmonary arterial hypertension Dermatologic reactions: Stevens-Johnson syndrome, erythema multiforme

Mechanism of Action

Dasatinib is an inhibitor of multiple tyrosine kinases. It is used for the treatment of all phases of chronic myeloid leukaemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL) in adults who have resistance or intolerance to previous therapy, including imatinib.