Apo-Dasatinib

Dasatinib

Adults w/ newly diagnosed Philadelphia chromosome +ve (Ph+) chronic myeloid leukemia (CML) in chronic phase. Adults w/ Ph+ chronic, accelerated, or blast phase CML w/ resistance or intolerance to prior therapy including imatinib mesylate. Adults w/ Ph+ acute lymphoblastic leukemia (ALL) w/ resistance or intolerance to prior therapy.

Chronic phase CML Recommended starting dose: 100 mg once daily, either in the morning or evening. Accelerated phase CML; myeloid or lymphoid blast CML; Ph+ ALL Recommended starting dose: 140 mg once daily, either in the morning or evening.

May be taken with or without food: Swallow whole. Do not crush/cut.

Hypersensitivity. Lactation.

Risk of cardiac adverse reactions; fluid retention; hemorrhage; HBV reactivation; myelosuppression; pulmonary arterial HTN; rhabdomyolysis w/ acute renal failure; severe mucocutaneous dermatologic reactions, including SJS & erythema multiforme. Evaluate patients w/ risk factors or a history of cardiac disease at baseline & monitor carefully for clinical signs or symptoms consistent w/ cardiac dysfunction during routine follow-up. Administer w/ caution in patients who have or may develop QTc prolongation, including patients w/ hypokalemia or hypomagnesemia, patients w/ congenital long QT syndrome, patients taking antiarrhythmics or other medicinal products that lead to QT prolongation, & cumulative high-dose anthracycline therapy. Correct hypokalemia or hypomagnesemia prior to administration of treatment. Test patients for HBV infection before initiating treatment. Closely monitor HBV carriers for signs & symptoms of active HBV infection throughout therapy & for several mth following termination of therapy. Perform CBCs every 2 wk for 12 wk, then every 3 mth thereafter or as clinically indicated in patients w/ chronic phase CML. Perform CBCs wkly for the 1st 2 mth & then mthly thereafter or as clinically indicated in patients w/ advanced phase CML or Ph+ ALL. Perform hepatic function tests (AST, ALT & bilirubin), CK & renal function tests every 2 wk for the 1st 2 mth & then mthly thereafter or as clinically indicated. Evaluate patients for signs & symptoms of underlying cardiopulmonary disease prior to initiation of therapy. Avoid concomitant use w/ strong CYP3A4 inhibitors; potent CYP3A4 inducers; grapefruit or grapefruit juice. Caution when co-administered w/ drugs that potentially alter CYP3A4 activity, QTc prolongers, or CYP3A4 substrates of narrow therapeutic index eg, cyclosporine, macrolides, benzodiazepine, pimozide, or ergot alkaloids (ergotamine, dihydroergotamine); anticoagulants. Consider antacids in place of H2 antagonists or PPIs in patients receiving dasatinib therapy. Al hydroxide/Mg hydroxide products may be administered up to 2 hr prior to, or 2 hr following dasatinib administration. No safety information on concomitant use w/ antiemetics (prochlorperazine, metoclopramide, 5-HT3 inhibitors). Should not be taken by patients w/ rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. Caution in patients w/ moderate to severe hepatic impairment. Can cause fetal harm when administered to pregnant women. Sexually active male patients or women of childbearing potential should use highly effective contraception during treatment. Not recommended in childn <18 yr.

Pyrexia, fatigue, pain, asthenia, chest pain, generalized edema; diarrhea, nausea, abdominal pain, vomiting, dyspepsia, mucosal inflammation (including mucositis/stomatitis), constipation, ascites; URTI/inflammation, infection (including bacterial, viral, fungal, non-specified), enterocolitis infection; musculoskeletal pain, myalgia, arthralgia; rash, pruritus, hyperhidrosis; cough, pleural effusion, dyspnea, pulmonary HTN, pulmonary edema; headache, neuropathy (including peripheral neuropathy), dizziness; hemorrhage (including bleeding), HTN; increased wt; CHF/cardiac dysfunction, pericardial effusion; insomnia, depression; appetite disturbances. Newly diagnosed chronic phase CML: Face edema, peripheral edema; gastritis, abdominal distension; muscle spasms; dermatitis (including eczema), pigmentation disorder, acne; conjunctivitis. Imatinib-intolerant or -resistant chronic phase CML: Superficial edema, chills; abdominal distension; pneumonia (including bacterial, viral, & fungal), herpes virus infection; muscle spasms, arthritis; alopecia, dry skin, acne; flushing; decreased wt; arrhythmia (including tachycardia), palpitations; anxiety; hyperuricemia; visual disorder; urinary frequency; hypersensitivity (including erythema nodosum). Imatinib-intolerant or -resistant advanced phase CML & Ph+ ALL: Superficial edema; pneumonia (including bacterial, viral, & fungal), sepsis (including fatal outcomes); dry skin; lung infiltration; hypotension; decreased wt; arrhythmia (including tachycardia); anxiety; renal failure; febrile neutropenia; contusion.

Decreased metabolism & increased conc w/ CYP3A4 inhibitors (eg, ketoconazole, itraconazole, erythromycin, clarithromycin, grapefruit juice). Reduced exposure w/ CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarb, St. John's wort). Decreased C_max & AUC w/ Al hydroxide/Mg hydroxide; famotidine. Increased C_max & AUC of simvastatin (CYP3A4 substrate). Additive risk of QT prolongation & torsades de pointes w/ medicinal products known to prolong QTc interval or induce torsades de pointes eg, class IA antiarrhythmics (eg, disopyramide, procainamide), class III antiarrhythmics (eg, amiodarone, sotalol, ibutilide), class IC antiarrhythmics (eg, flecainide), antipsychotics (eg, chlorpromazine, haloperidol, pimozide), opioids (eg, methadone), macrolides (eg, erythromycin, clarithromycin), quinolones (eg, moxifloxacin), antimalarials (eg, chloroquine), GI stimulants or others (eg, domperidone).

Targeted Cancer Therapy

L01EA02 - dasatinib ; Belongs to the class of BCR-ABL tyrosine kinase inhibitors. Used in the treatment of cancer.

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