• Chronic phase Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) that is either newly diagnosed or resistant/intolerant to prior therapy including imatinib.
• Accelerated, or myeloid or lymphoid blast phase Ph+ CML resistant/intolerant to prior therapy including imatinib.
• Ph+ acute lymphoblastic leukemia (ALL) that is either newly diagnosed (children) or resistant/intolerant to prior therapy (adults).

Contraindicated in:

• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• ↑risk of QTc prolongation including hypokalemia, hypomagnesemia, congenital prolonged QT syndrome, concurrent antiarrhythmic drugs, or other drugs that prolong QT interval, including cumulative high-dose anthracycline therapy (correct electrolyte abnormalities prior to use)
• Concurrent use of anticoagulants or agents that inhibit platelet function
• Women of reproductive potential and men with female partners of reproductive potential.

CV: edema, HF, MI, QTc interval prolongation, hypertension, hypotension, palpitations.

Derm: rash, acne, alopecia, dry skin, ERYTHEMA MULTIFORME, flushing, nail disorder, PALMAR-PLANTAR ERYTHRODYSESTHESIA , photosensitivity, pigment disorder, STEVENS-JOHNSON SYNDROME, sweating, urticaria.

EENT: conjunctivitis, dry eye, tinnitus.

Endo: gynecomastia.

F and E: hypocalcemia.

GI: ↑liver enzymes, diarrhea, nausea, abdominal pain, ascites, dyspepsia, ileus, mucositis, vomiting.

GU: RENAL FAILURE, urinary frequency.

Hemat: anemia, neutropenia, thrombocytopenia, BLEEDING.

Metab: ↓growth (children), altered appetite, hyperuricemia.

MS: musculoskeletal pain, muscle inflammation/weakness.

Neuro: fatigue, headache, altered affect, anxiety, confusion, depression, drowsiness, dysgeusia, insomnia, malaise, SEIZURES, syncope, tremor, vertigo.

Resp: dyspnea, asthma, pleural effusion, pneumonitis, PULMONARY EDEMA, PULMONARY HYPERTENSION.
Misc: fever, (INCLUDING HEPATITIS B VIRUS REACTIVATION)INFECTION, TUMOR LYSIS SYNDROME.

Drug-Drug:

• CYP3A4 inhibitors, including ketoconazole, itraconazole, clarithromycin, ritonavir, atazanavir, nefazodone, nelfinavir, and voriconazole, may ↑ levels and risk of toxicity; concurrent use should be avoided. If concurrent use is required, ↓ dose of dasatinib may be required.
• CYP3A4 inducers, including dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, and phenobarbital, may ↓ levels and effectiveness; concurrent use should be avoided. If concurrent use is required, ↑ dose of dasatinib may be required.
• Antacids may alter absorption; simultaneous use should be avoided (dose 2 hr prior to or 2 hr after dasatinib).
• H₂ antagonists and proton pump inhibitors may also ↓ absorption and should be avoided; consider antacids as an alternative.
• Cyclosporine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, or ergot alkaloids (ergotamine, dihydroergotamine) should be administered with caution because of their narrow therapeutic indices and the unpredictability of enzyme induction/inhibition.

Drug-Natural Products:

• St. John's wort may ↓ levels and effectiveness; avoid concurrent use.

Drug-Food:

• Grapefruit juice may ↑ levels and risk of toxicity; avoid concurrent use.

(Generic available)

• Tablets: 20 mg; 50 mg; 70 mg; 80 mg; 100 mg; 140 mg;

Accelerated, or Myeloid or Lymphoid Blast Phase Ph+ Chronic Myeloid Leukemia

• PO (Adults): 140 mg once daily; may ↑ to 180 mg once daily if hematologic or cytogenetic response is not achieved; continue until disease progression or unacceptable toxicity; Concurrent strong CYP3A4 inhibitor: 40 mg once daily; continue until disease progression or unacceptable toxicity.

Chronic Phase Ph+ Chronic Myeloid Leukemia

• PO (Adults): 100 mg once daily; may ↑ to 140 mg once daily if hematologic or cytogenetic response is not achieved; continue until disease progression or unacceptable toxicity; Concurrent strong CYP3A4 inhibitor: 20 mg once daily; continue until disease progression or unacceptable toxicity.
• PO (Children 45 kg): 100 mg once daily; may ↑ to 120 mg once daily if hematologic or cytogenetic response is not achieved; continue until disease progression or unacceptable toxicity; Concurrent strong CYP3A4 inhibitor: 20 mg once daily; continue until disease progression or unacceptable toxicity.
• PO (Children 30–<45 kg): 70 mg once daily; may ↑ to 90 mg once daily if hematologic or cytogenetic response is not achieved; continue until disease progression or unacceptably toxicity; Concurrent strong CYP3A4 inhibitor: 20 mg once daily; continue until disease progression or unacceptable toxicity.
• PO (Children 20–<30 kg): 60 mg once daily; may ↑ to 70 mg once daily if hematologic or cytogenetic response is not achieved; continue until disease progression or unacceptable toxicity; Concurrent strong CYP3A4 inhibitor: Discontinue dasatinib and then reinitiate 1 wk after discontinuing CYP3A4 inhibitor.
• PO (Children 10–<20 kg): 40 mg once daily; may ↑ to 50 mg once daily if hematologic or cytogenetic response is not achieved; continue until disease progression or unacceptable toxicity; Concurrent strong CYP3A4 inhibitor: Discontinue dasatinib and then reinitiate 1 wk after discontinuing CYP3A4 inhibitor.

Ph+ Acute Lymphoblastic Leukemia

• PO (Adults): 140 mg once daily; may ↑ to 180 mg once daily if hematologic or cytogenetic response is not achieved; continue until disease progression or unacceptable toxicity; Concurrent strong CYP3A4 inhibitor: 40 mg once daily; continue until disease progression or unacceptable toxicity.
• PO (Children 45 kg): 100 mg once daily started on or before Day 15 of induction chemotherapy; continue for 2 yr; Concurrent strong CYP3A4 inhibitor: 20 mg once daily started on or before Day 15 of induction chemotherapy; continue for 2 yr.
• PO (Children 30–<45 kg): 70 mg once daily started on or before Day 15 of induction chemotherapy; continue for 2 yr; Concurrent strong CYP3A4 inhibitor: 20 mg once daily started on or before Day 15 of induction chemotherapy; continue for 2 yr.
• PO (Children 20–<30 kg): 60 mg once daily started on or before Day 15 of induction chemotherapy; continue for 2 yr; Concurrent strong CYP3A4 inhibitor: Discontinue dasatinib and then reinitiate 1 wk after discontinuing CYP3A4 inhibitor.
• PO (Children 10–<20 kg): 40 mg once daily started on or before Day 15 of induction chemotherapy; continue for 2 yr; Concurrent strong CYP3A4 inhibitor: Discontinue dasatinib and then reinitiate 1 wk after discontinuing CYP3A4 inhibitor.

Phyrago, Sprycel

• Inhibits tyrosine kinases resulting in inhibition of leukemic cell lines, including those resistant to imatinib.

• Decreased progression of leukemias.

Therapeutic Classification: antineoplastics

Pharmacologic Classification: enzyme inhibitors

Absorption: Well absorbed following oral administration. Absorption is pH dependent.

Distribution: Extensively distributed into extravascular space.

Protein Binding: 96%.

Metabolism/Excretion: Extensively metabolized, mostly by the CYP3A4 enzyme system. 85% eliminated in feces, mostly as metabolites; 4% eliminated in urine, mostly as metabolites.

Half-life: 3–5 hr.

• Explain purpose of dasatinib. Instruct patient to take dasatinib at the same time each day. Do not stop or change dose without consulting health care professional. If a dose is missed, omit and take next scheduled dose at regular time; do not double doses. Advise patient to read the Patient Information sheet prior to starting therapy and with each Rx refill in case of changes.
• Advise patient to avoid grapefruit and grapefruit juice during therapy; may increase risk of toxicity.
• Advise patient to notify health care professional immediately if signs and symptoms of infection (fever); bleeding (unusual bleeding, easy bruising); fluid retention (swelling, weight gain, dry cough, chest pain on respiration, shortness of breath); pulmonary arterial hypertension (shortness of breath, fatigue, hypoxia, swelling of ankles and legs); tumor lysis syndrome (nausea, vomiting, weakness, edema, shortness of breath, muscle cramps, seizures); rash; or bone growth abnormalities, bone pain, or gynecomastia in pediatric patients occur.
• May cause dizziness. Caution patients to avoid driving or other activities requiring alertness until response to medication is known.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken or if lactose intolerant and consult health care professional before taking any new medications, especially St. John's wort. Advise patients to avoid taking medicines that reduce stomach acid to improve absorption. Medicines that neutralize stomach acid, such as antacids, may be used up to 2 hr before or 2 hr after dasatinib dose.
• Inform patient that headache and musculoskeletal pain may occur; notify health care professional if severe.
• May cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during therapy and for 30 days after final dose and to avoid breastfeeding during and for 2 wk after final dose. Advise patient notify health care professional if pregnancy is planned or suspected. Women who are pregnant or may become pregnant should avoid handling crushed or broken tablets. May cause damage to female and male reproductive tissues causing infertility.

da-SAti-nib