Dasatinib

Oral
Chronic myeloid leukaemia

No dosage adjustment needed.

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

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.

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.

Reversible myelosuppression, neutropenia, anaemia, thrombocytopenia, fluid retention, pulmonary arterial HTN, QT prolongation, cardiac failure, arrhythmias, HTN, musculoskeletal pain, GI disturbances, headache, chills, fatigue, asthenia, myalgia, chest pain, arthralgia, pyrexia, mucositis, flushing, colitis, electrolyte disturbances, appetite and wt disturbances, rash, dermatitis, hyperhidrosis, pruritus, acne.
Potentially Fatal: Severe bleeding events, including fatal CNS and GI haemorrhages; MI. Uncommon: Sepsis.

PO: D

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.

Symptoms: Significant platelet count reduction. Management: Closely monitor for myelosuppression. Supportive and symptomatic treatment.

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).

Avoid St John's wort as it may decrease dasatinib levels. Avoid grapefruit juice as it may increase dasatinib levels.

Description:
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.
Pharmacokinetics:
Absorption: Time to peak plasma concentration: 0.5-6 hr.
Distribution: Volume of distribution: 2505 L. Plasma protein binding: Approx 96% (dasatinib); approx 93% (active metabolite).
Metabolism: Extensively hepatic via CYP3A4 isoenzyme to form its active metabolite.
Excretion: Via faeces (approx 85%, 19% as unchanged drug); urine (approx 4%, 0.1% as unchanged drug).

Store at 25°C.

Targeted Cancer Therapy

Anon. Dasatinib. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 30/10/2013.

Anon. Dasatinib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 30/10/2013.

Buckingham R (ed). Dasatinib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 30/10/2013.

Joint Formulary Committee. Dasatinib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 30/10/2013.

Sprycel (Dasatinib): Drug Safety Communication - Risk of Pulmonary Arterial Hypertension. U.S. FDA. https://www.fda.gov/. Accessed 30/10/2013.