a) During clinical trials, 16 of 2440 patients (less than 1%) treated with dasatinib reported QTc prolongation, and 22 patients (1%) developed a QTcF greater than 500 msec. During 5 phase 2 single-arm studies, involving 865 patients with leukemia who were treated with dasatinib, the maximum mean changes in the QTcF from baseline ranged from 7 to 13.4 msec (Prod Info SPRYCEL(R) oral tablets, 2015).

a) During clinical trials, fluid retention (all grades) and grade 3 or 4 fluid retention were reported in 38% and 5%, respectively, of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).
b) In clinical trials of chronic myeloid leukemia (CML) patients with prior imatinib resistance or intolerance, fluid retention (all grades) and grade 3 or 4 fluid retention occurred in 48% and 7% of chronic phase CML patients (n=165) treated with dasatinib 100 mg once daily, respectively. Among patients with advanced phase CML treated with dasatinib 140 mg once daily, fluid retention (all grades) occurred in 35%, 34%, and 21% of those in the accelerated phase (n=157), myeloid blast phase (n=74), or lymphoid blast phase (n=33), respectively. Grade 3 or 4 fluid retention occurred in 8%, 7%, and 6% of these patients respectively (Prod Info SPRYCEL(R) oral tablets, 2015).

a) During clinical trials, pericardial effusion (all grades) and grade 3 or 4 pericardial effusion were reported in 4% and 1%, respectively, of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).
b) In clinical trials of chronic myeloid leukemia (CML) patients with prior imatinib resistance or intolerance, pericardial effusion (all grades) and grade 3 or 4 pericardial effusion occurred in 3% and 1% of chronic phase CML patients (n=165) treated with dasatinib 100 mg once daily, respectively. Among patients with advanced phase CML treated with dasatinib 140 mg once daily, pericardial effusion (all grades) and grade 3 or 4 pericardial effusion occurred in 3% and 1%, respectively, of patients in the accelerated phase (n=157), (Prod Info SPRYCEL(R) oral tablets, 2015).

a) During clinical trials, congestive heart failure or cardiac dysfunction, including cardiomyopathy, diastolic dysfunction, decreased ejection fraction, and left ventricular dysfunction (all grades), and grade 3 or 4 congestive heart failure or cardiac dysfunction were reported in 2% and less than 1%, respectively, of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).

a) In clinical trials of chronic myeloid leukemia (CML) patients with prior imatinib resistance or intolerance, dyspnea (all grades) and grade 3 or 4 dyspnea occurred in 24% and 2% of chronic phase CML patients (n=165) treated with dasatinib 100 mg once daily, respectively. Among patients with advanced phase CML treated with dasatinib 140 mg once daily, dyspnea (all grades) occurred in 20%, 15%, and 3% of those in the accelerated phase (n=157), myeloid blast phase (n=74), or lymphoid blast phase (n=33), respectively. Grade 3 or 4 dyspnea occurred in 3% of patients in all of the groups (Prod Info SPRYCEL(R) oral tablets, 2015).

a) During clinical trials, pulmonary hypertension (all grades) and grade 3 or 4 pulmonary hypertension were reported in 5% and 1%, respectively, of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).
b) In clinical trials of chronic myeloid leukemia (CML) patients with prior imatinib resistance or intolerance, pulmonary hypertension (all grades) and grade 3 or 4 pulmonary hypertension occurred in 2% and 1% of chronic phase CML patients (n=165) treated with dasatinib 100 mg once daily, respectively (Prod Info SPRYCEL(R) oral tablets, 2015).
c) CASE REPORT: A 46-year-old woman with chronic myelogenous leukemia developed exertional dyspnea with chest pain and peripheral edema 3 months after beginning dasatinib therapy. A chest x-ray revealed prominent pulmonary arteries, suggesting pulmonary hypertension, and an ECG showed right axis deviation with T-wave inversion. A transthoracic echocardiogram demonstrated right chamber enlargement with elevated right ventricle systolic pressure, and a chest CT revealed pulmonary artery enlargement without evidence of pulmonary embolism. Following discontinuation of dasatinib, the patient's symptoms gradually improved over the next 6 months (Yun et al, 2014).
d) CASE REPORT: A 50-year-old man, who received dasatinib therapy in combination with other chemotherapeutic agents (ie, 6-mercaptopurine, vincristine, methotrexate, and prednisone) over a 2-year-period for treatment of acute lymphoblastic leukemia, developed exertional dyspnea and fatigue. Despite a medication switch to nilotinib and administration of furosemide and prednisolone for 3 weeks, the patient's symptoms increased resulting in hospitalization 1 month later. A chest x-ray demonstrated cardiomegaly with bilateral pleural effusion, an ECG revealed a right bundle branch block. A transthoracic echocardiogram revealed an enlarged right heart chambers with a systolic pulmonary artery pressure of 70 mmHg, and right heart catheterization indicated severe precapillary pulmonary arterial hypertension. Following an increase in the dose of furosemide and initiating treatment with bosentan, at a dose of 2 62.5-mg tablets daily and increasing to 2 125-mg tablets daily, the patient gradually recovered. A repeat echocardiogram indicated normal systolic pulmonary artery pressure and normal right ventricular function and dimension. Two months after discontinuation of dasatinib therapy, the patient was asymptomatic with NYHA class I functional capacity (Tacoy et al, 2015).

a) During clinical trials, pleural effusion (all grades) and grade 3 or 4 pleural effusion were reported in 28% and 3%, respectively, of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).
b) In clinical trials of chronic myeloid leukemia (CML) patients with prior imatinib resistance or intolerance, pleural effusion (all grades) and grade 3 or 4 pleural effusion occurred in 28% and 5% of chronic phase CML patients (n=165) treated with dasatinib 100 mg once daily, respectively. Among patients with advanced phase CML treated with dasatinib 140 mg once daily, pleural effusion (all grades) occurred in 21%, 20%, and 21% of those in the accelerated phase (n=157), myeloid blast phase (n=74), or lymphoid blast phase (n=33), respectively. Grade 3 or 4 pleural effusion occurred in 7%, 7%, and 6% of these patients, respectively (Prod Info SPRYCEL(R) oral tablets, 2015).

a) During clinical trials, pulmonary edema (all grades) was reported in 1% of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).
b) In clinical trials of patients with advanced phase chronic myeloid leukemia (CML), with prior imatinib resistance or intolerance, treated with dasatinib 140 mg once daily, pulmonary edema (all grades) occurred in 1%, and 4% of those in the accelerated phase (n=157) or myeloid blast phase (n=74), respectively (Prod Info SPRYCEL(R) oral tablets, 2015).

a) During clinical trials, headache (all grades) was reported in 14% of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).
b) In clinical trials of chronic myeloid leukemia (CML) patients with prior imatinib resistance or intolerance, headache (all grades) and grade 3 or 4 headache occurred in 33% and 1% of chronic phase CML patients (n=165) treated with dasatinib 100 mg once daily, respectively. Among patients with advanced phase CML treated with dasatinib 140 mg once daily, headache (all grades) occurred in 27%, 18%, and 15% of those in the accelerated phase (n=157), myeloid blast phase (n=74), or lymphoid blast phase (n=33), respectively. Grade 3 or 4 headache occurred in 1%, 1%, and 3% of these patients, respectively (Prod Info SPRYCEL(R) oral tablets, 2015).

a) During clinical trials, CNS bleeding (all grades) was reported in less than 1% of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).
b) In clinical trials of patients with advanced phase chronic myeloid leukemia (CML), with prior imatinib resistance or intolerance, treated with dasatinib 140 mg once daily, CNS bleeding (all grades) occurred in 1% and 3% of those in the accelerated phase (n=157) or lymphoid blast phase (n=33), respectively (Prod Info SPRYCEL(R) oral tablets, 2015).

a) Neuropathy, including peripheral neuropathy, was reported in 1% to less than 10% of patients treated with dasatinib therapy across all clinical studies (Prod Info SPRYCEL(R) oral tablets, 2015).

a) During clinical trials, nausea and vomiting (all grades) were reported in 10% and 5%, respectively, of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).
b) In clinical trials of chronic myeloid leukemia (CML) patients with prior imatinib-resistance or -intolerance, nausea (all grades) was reported in 18% of chronic phase CML patients receiving dasatinib 100 mg once daily (n=165). Grade 3 or 4 nausea was reported in 1% of patients (Prod Info SPRYCEL(R) oral tablets, 2015).
c) Among patients with advanced phase CML treated with dasatinib 140 mg daily, nausea and vomiting (all grades) occurred in 19% and 11% of patients in the accelerated phase (n=157), respectively, 23% and 12% of patients in the myeloid blast phase (n=74), respectively, and 21% and 15% of patients in the lymphoid blast phase (n=33). respectively (Prod Info SPRYCEL(R) oral tablets, 2015).

a) During clinical trials, diarrhea (all grades) was reported in 22% of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).
b) In clinical trials of chronic myeloid leukemia (CML) patients with prior imatinib resistance or intolerance, diarrhea (all grades) and grade 3 or 4 diarrhea occurred in 28% and 2% of chronic phase CML patients (n=165) treated with dasatinib 100 mg once daily, respectively. Among patients with advanced phase CML treated with dasatinib 140 mg once daily, diarrhea (all grades) occurred in 31%, 20%, and 18% of those in the accelerated phase (n=157), myeloid blast phase (n=74), or lymphoid blast phase (n=33), respectively. Grade 3 or 4 diarrhea occurred in 3%, 5%, and 0% of these patients respectively (Prod Info SPRYCEL(R) oral tablets, 2015).

a) During clinical trials, abdominal pain (all grades) was reported in 11% of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).
b) In clinical trials of chronic myeloid leukemia (CML) patients with prior imatinib resistance or intolerance, abdominal pain (all grades) occurred in 12% of chronic phase CML patients (n=165) treated with dasatinib 100 mg once daily (Prod Info SPRYCEL(R) oral tablets, 2015).

a) During clinical trials, gastrointestinal bleeding (all grades) was reported in 2% of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).
b) In clinical trials of chronic myeloid leukemia (CML) patients with prior imatinib resistance or intolerance, gastrointestinal bleeding (all grades) occurred in 2% of chronic phase CML patients (n=165) treated with dasatinib 100 mg once daily. Among patients with advanced phase CML treated with dasatinib 140 mg once daily, gastrointestinal bleeding (all grades) occurred in 8%, 9%, and 9% of those in the accelerated phase (n=157), myeloid blast phase (n=74), or lymphoid blast phase (n=33), respectively. Grade 3 or 4 gastrointestinal bleeding occurred in 6%, 7%, and 3% of these patients, respectively (Prod Info SPRYCEL(R) oral tablets, 2015).
c) Gastrointestinal bleeding was reported as serious in 7% of Philadelphia chromosome-positive acute lymphoblastic leukemia patients treated with dasatinib (n=135) during clinical trials (Prod Info SPRYCEL(R) oral tablets, 2015).

a) In clinical trials of chronic myeloid leukemia (CML) patients with prior imatinib resistance or intolerance, constipation (all grades) occurred in 10% of chronic phase CML patients (n=165) treated with dasatinib 100 mg once daily (Prod Info SPRYCEL(R) oral tablets, 2015).

a) Mucosal inflammation, including mucositis/stomatitis, was reported in 1% to less than 10% of patients treated with dasatinib therapy across all clinical studies (Prod Info SPRYCEL(R) oral tablets, 2015).

a) CASE REPORT: An 8-year-old girl with Philadelphia chromosome-positive (Ph+) acute lymphoid leukemia (ALL) developed hemorrhagic colitis during treatment with dasatinib. The patient's medical history included diagnosis at the age of 3 years and 8 months, induction and reinduction with conventional chemotherapeutic courses with concomitant imatinib therapy, 2 bone marrow transplant (BMT) relapses, and imatinib resistance after the second BMT at the age of 8 years and 3 months with molecular relapse. At the age of 8 years and 6 months the patient started dasatinib 30 mg (40 mg/m(2)) orally twice daily and the patient achieved molecular remission. After 3 weeks of dasatinib therapy, the patient developed nausea, vomiting, fresh bloody diarrhea, and anemia without thrombocytopenia, coagulation abnormalities or other bleeding symptoms. Repeated stool analyses were negative for parasitic worm eggs, amoeba, Clostridium difficile, and pathogenic bacteria. Ganciclovir therapy induced cytomegalovirus antigen negativity; however, the hemorrhagic diarrhea did not resolve. Colonoscopy showed blood exuding through normal-appearing mucosa with preserved vascular markings and ulceration absent. Mucosal biopsy showed nonspecific colitis. The addition of oral prednisolone 30 mg/day (2 mg/kg) improved the bloody diarrhea in a few days, and the dose was gradually decreased to 4 mg/day. After the confirmation of cytogenetic and molecular remission 8 months later, dasatinib and prednisolone were withdrawn due to pericardial effusion. One month later, the patient experienced an isolated CNS relapse. Soon after dasatinib was reintroduced, the severe hemorrhagic diarrhea recurred. Dasatinib was discontinued and the administration of prednisolone 30 mg/day resolved the symptoms. Dasatinib-related hemorrhagic colitis was suspected due to recurrence upon dasatinib rechallenge (Shimokaze et al, 2009).
b) CASE REPORT: A 47-year-old woman, with Philadelphia chromosome positive chronic myeloid leukemia blast crisis with acute lymphoblastic leukemia, developed episodic diarrhea with hematochezia 1 month after beginning dasatinib therapy at a dose of 70 mg/day. Infectious colitis was suspected due to the development of tender abdomen, tachycardia, and mild fever; however, abdominal CT scan was normal and tests for enteric pathogenic organisms were negative. Laboratory data reported a hemoglobin level of 11.2 g/d and a platelet count of 157,000/mcL. Prothrombin time, INR, and activated partial thromboplastin time were normal. Four months later, she presented with bloody diarrhea. A colonoscopy revealed congested, erythematous, and granular mucosa from the rectum to the colon, although a biopsy indicated no active colitis. Dasatinib was continued, however, her diarrhea progressively worsened, and she developed abdominal cramps, dehydration, and anemia. Laboratory data revealed a hemoglobin level of 6.5 g/dL and a platelet count of 90,000 mc/L. A repeat colonoscopy revealed mild congestion with decreased mucosa that was erythematous and granular and histopathology demonstrated colonic mucosa with increased inflammation of the lamina propria and areas of intraepithelial lymphocytes, leading to a diagnosis of hemorrhagic colitis secondary to dasatinib therapy. The diarrhea resolved following discontinuation of the dasatinib for 2 weeks, but recurred when dasatinib was restarted at a lower dose (50 mg/day). Cessation of the dasatinib and administration of steroids resulted in resolution of symptoms. Restarting dasatinib at a dose of 20 mg/day was well-tolerated with no evidence of gastrointestinal or systemic effects (Chisti et al, 2013).

a) During clinical trials, grade 3 or 4 elevated ALT or AST concentrations were reported in less than 1% of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).
b) In clinical trials of patients with advanced phase chronic myeloid leukemia (CML), with prior imatinib resistance or intolerance, treated with dasatinib 140 mg once daily, grade 3 or 4 elevated ALT concentrations occurred in 2%, 5%, and 3% of those in the accelerated phase (n=157), myeloid blast phase (n=74), or lymphoid blast phase (n=33), respectively (Prod Info SPRYCEL(R) oral tablets, 2015).
c) In clinical trials of chronic myeloid leukemia (CML) patients with prior imatinib-resistance or -intolerance, grade 3 or 4 elevated AST concentrations were reported in less than 1% of chronic phase CML patients receiving dasatinib 100 mg once daily (n=165). In patients with advanced phase CML treated with dasatinib 140 mg daily, 4% and 3% of patients in the myeloid blast phase (n=74) or lymphoid blast phase (n=33). respectively, reported grade 3 or 4 elevated AST concentrations (Prod Info SPRYCEL(R) oral tablets, 2015).

a) During clinical trials, grade 3 or 4 elevated bilirubin concentrations were reported in 1% of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).
b) In clinical trials of chronic myeloid leukemia (CML) patients with prior imatinib-resistance or -intolerance, grade 3 or 4 elevated bilirubin concentrations were reported in less than 1% of chronic phase CML patients receiving dasatinib 100 mg once daily (n=165). In patients with advanced phase CML treated with dasatinib 140 mg daily, 1%, 3%, and 6% of patients in the accelerated phase (n=157), myeloid blast phase (n=74), or lymphoid blast phase (n=33). respectively, reported grade 3 or 4 elevated bilirubin concentrations (Prod Info SPRYCEL(R) oral tablets, 2015).

a) CASE REPORT: A 43-year-old man with Philadelphia chromosome-positive, chronic myeloid leukemia (CML) experienced an episode of hepatitis following treatment with dasatinib. The patient had received an autologous peripheral blood stem-cell transplant for CML due to interferon therapy failure and had a history of alcohol-induced hepatitis while on interferon therapy. He received dasatinib 100 mg/day after developing persistent lower limb cramps, chronic diarrhea, and moderate fluid retention with imatinib therapy. When dasatinib was started, the patient had an alcohol consumption of 40 g/week and had been taking zopiclone for 2 years. Initially the patient had severe diarrhea with abdominal pain, weight loss, and anorexia; however, dasatinib was continued and these symptoms resolved within 1 month. The patient was noted to have a transient cutaneous rash 4 months after starting dasatinib; also at this time, he had normal liver function tests and was in a complete cytogenic remission. The patient complained of asthenia, anorexia, and daily diarrhea about 5 months after starting dasatinib, and he was diagnosed with moderate mixed acute hepatitis (with transaminase levels 10 times the upper limit of normal). He was admitted to the hospital approximately 2 months later. On admission, laboratory tests showed elevated liver function tests (ALT, 758 international units/L; AST, 761 international units/L; alkaline phosphatase, 1432 international units/L, total bilirubin, 25 mcmol/L) but the patient showed no overt signs of liver failure. No liver biopsy was performed. Dasatinib was discontinued and liver function tests returned to within the normal range in 3 weeks. Five months after dasatinib was discontinued, the patient remained asymptomatic with normal liver function tests (Bonvin et al, 2008).

a) During clinical trials, grade 3 or 4 elevated creatinine concentrations were reported in 1% of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).
b) In clinical trials of patients with advanced phase chronic myeloid leukemia (CML), with prior imatinib resistance or intolerance, treated with dasatinib 140 mg once daily, grade 3 or 4 elevated creatinine concentrations occurred in 2% and 8% of those in the accelerated phase (n=157), or myeloid blast phase (n=74), respectively (Prod Info SPRYCEL(R) oral tablets, 2015).

a) CASE REPORT: A 67-year-old woman developed acute renal failure following treatment with dasatinib for chronic myeloid leukemia. The patient had been treated with dasatinib 50 mg/day for one month when she presented to the hospital with diarrhea, nausea, and vomiting. On physical examination, the patient had normal oral mucosa and skin turgor and tonus; additionally, her urine output was 1200 cubic centimeters/day. Laboratory values at presentation included a hemoglobin level of 8.8 g/dL, a sodium level of 134 mEq/L, a potassium level of 5.2 mEq/L, a BUN level of 77 mg/dL, a serum creatinine level of 4.9 mg/dL, a blood pH of 7.19, and a bicarbonate (HCO3) level of 8.7 mmol/L. A renal biopsy revealed microscopic findings consistent with acute tubular necrosis. Ten days after dasatinib was discontinued and conservative treatment was initiated, the patient’s gastroenteritis symptoms resolved and her laboratory values were as follows: BUN level of 26 mg/dL, serum creatinine level of 1.6 mg/dL, blood pH of 7.49, and a HCO3 level of 26.1 mmol/L. Nilotinib 400 mg twice daily was initiated, and no side effects or pathological clinical findings were observed after 3 months of follow-up (Ozkurt et al, 2010).

a) In one study of 84 patients, myelosuppression required interruption of treatment in about 60% of patients, but usually resolved within 3 months (Talpaz et al, 2006).

a) Severe myelosuppression and bleeding were reported in 2 patients who ingested dasatinib 280 mg/day for 1 week (Prod Info SPRYCEL(R) oral tablets, 2015).

a) During clinical trials, grade 3 or 4 neutropenia was reported in 29% of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).
b) In clinical trials of chronic myeloid leukemia (CML) patients with prior imatinib-resistance or -intolerance, grade 3 or 4 neutropenia was reported in 36% of chronic phase CML patients receiving dasatinib 100 mg once daily (n=165). In patients with advanced phase CML treated with dasatinib 140 mg daily, 58%, 77%, and 79% of patients in the accelerated phase (n=157), myeloid blast phase (n=74), or lymphoid blast phase (n=33). respectively, reported grade 3 or 4 neutropenia (Prod Info SPRYCEL(R) oral tablets, 2015).

a) During clinical trials, grade 3 or 4 thrombocytopenia was reported in 22% of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).
b) In clinical trials of chronic myeloid leukemia (CML) patients with prior imatinib-resistance or -intolerance, grade 3 or 4 thrombocytopenia was reported in 24% of chronic phase CML patients receiving dasatinib 100 mg once daily (n=165). In patients with advanced phase CML treated with dasatinib 140 mg daily, 63%, 78%, and 85% of patients in the accelerated phase (n=157), myeloid blast phase (n=74), or lymphoid blast phase (n=33). respectively, reported grade 3 or 4 thrombocytopenia (Prod Info SPRYCEL(R) oral tablets, 2015).

a) During clinical trials, grade 3 or 4 anemia was reported in 13% of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).
b) In clinical trials of chronic myeloid leukemia (CML) patients with prior imatinib-resistance or -intolerance, grade 3 or 4 anemia was reported in 13% of chronic phase CML patients receiving dasatinib 100 mg once daily (n=165). In patients with advanced phase CML treated with dasatinib 140 mg daily, 47%, 74%, and 52% of patients in the accelerated phase (n=157), myeloid blast phase (n=74), or lymphoid blast phase (n=33). respectively, reported grade 3 or 4 anemia (Prod Info SPRYCEL(R) oral tablets, 2015).

a) In clinical trials of patients with advanced phase chronic myeloid leukemia (CML), with prior imatinib resistance or intolerance, treated with dasatinib 140 mg once daily, febrile neutropenia (all grades) occurred in 4%, 12%, and 12% of those in the accelerated phase (n=157), myeloid blast phase (n=74), or lymphoid blast phase (n=33), respectively. Grade 3 or 4 febrile neutropenia occurred in 4%, 12%, and 12%, of these patients, respectively (Prod Info SPRYCEL(R) oral tablets, 2015).
b) Febrile neutropenia was reported as serious adverse event in 6% of Philadelphia chromosome-positive acute lymphoblastic leukemia patients treated with dasatinib (n=135) during clinical trials. Median duration of treatment was 3 months (range 0.03 to 31 months)(Prod Info SPRYCEL(R) oral tablets, 2015).

a) Severe hemorrhages, including fatalities, occurred in patients treated with dasatinib during clinical studies. Less than 1% of patients in all clinical studies, experienced a severe CNS hemorrhage, 4% experienced a severe gastrointestinal hemorrhage, and 2% of patients experienced an unspecified severe hemorrhage. Most bleeding events were associated with severe thrombocytopenia (Prod Info SPRYCEL(R) oral tablets, 2015).
b) During clinical trials, bleeding (all grades), including conjunctival hemorrhage, ear hemorrhage, ecchymosis, epistaxis, eye hemorrhage, gingival bleeding, hematoma, hematuria, hemoptysis, intra-abdominal hematoma, petechiae, scleral hemorrhage, uterine hemorrhage, and vaginal hemorrhage, was reported in 6% of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).
c) In clinical trials of chronic myeloid leukemia (CML) patients with prior imatinib resistance or intolerance, hemorrhage (all grades) and grade 3 or 4 hemorrhage occurred in 12% and 1% of chronic phase CML patients (n=165) treated with dasatinib 100 mg once daily, respectively. Among patients with advanced phase CML treated with dasatinib 140 mg once daily, hemorrhage (all grades) occurred in 26%, 19%, and 24% of those in the accelerated phase (n=157), myeloid blast phase (n=74), or lymphoid blast phase (n=33), respectively. Grade 3 or 4 hemorrhage occurred in 8%, 9%, and 9%, of these patients respectively (Prod Info SPRYCEL(R) oral tablets, 2015).

a) Severe myelosuppression and bleeding were reported in 2 patients who ingested dasatinib 280 mg/day for 1 week (Prod Info SPRYCEL(R) oral tablets, 2015).

a) During clinical trials, rash (all grades), including erythema, erythema multiforme, generalized rash, macular rash, papular rash, pustular rash, skin exfoliation, and vesicular rash, was reported in 14% of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).
b) In clinical trials of chronic myeloid leukemia (CML) patients with prior imatinib resistance or intolerance, skin rash (all grades) and grade 3 or 4 skin rash occurred in 18% and 2% of chronic phase CML patients (n=165) treated with dasatinib 100 mg once daily, respectively. Among patients with advanced phase CML treated with dasatinib 140 mg daily, skin rash (all grades) occurred in 15%, 16%, and 21% of patients in the accelerated phase (n=157), myeloid blast phase (n=74), or lymphoid blast phase (n=33). respectively (Prod Info SPRYCEL(R) oral tablets, 2015).

a) In clinical trials of chronic myeloid leukemia (CML) patients with prior imatinib resistance or intolerance, pruritus (all grades) occurred in 12% of chronic phase CML patients (n=165) treated with dasatinib 100 mg once daily (Prod Info SPRYCEL(R) oral tablets, 2015).

a) CASE REPORT: Two patients with CML treated with dasatinib developed fever and a rash, consisting of painful subcutaneous nodules with overlying erythema, confirmed as lobular panniculitis on skin biopsy . In both patients the rash resolved when dasatinib was withdrawn and returned on rechallenge. In one patient, the rash could be suppressed with prednisone, in the other it could not (Assouline et al, 2006).

a) CASE REPORT: Bilateral depigmentation of the eyebrows, eyelashes, and temporal scalp hair was reported in a 29-year-old woman 6 to 8 weeks after initiation of dasatinib 70 mg/day orally for recurrent chronic myeloid leukemia (CML). The patient denied any changes in hair texture, and physical examination showed no skin dyspigmentation or changes in the nails or mucous membranes. Hair depigmentation is thought to be reversible upon drug discontinuation (Sun et al, 2009).

a) Alopecia was reported in 1% to less than 10% of patients treated with dasatinib therapy across all clinical studies (Prod Info SPRYCEL(R) oral tablets, 2015).

a) During clinical trials, musculoskeletal pain (all grades) was reported in 14% of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).
b) In clinical trials of chronic myeloid leukemia (CML) patients with prior imatinib resistance or intolerance, musculoskeletal pain (all grades) and grade 3 or 4 musculoskeletal pain occurred in 22% and 2% of chronic phase CML patients (n=165) treated with dasatinib 100 mg once daily, respectively. Among patients with advanced phase CML treated with dasatinib 140 mg once daily, musculoskeletal pain (all grades) occurred in 11% and 8% of those in the accelerated phase (n=157) or myeloid blast phase (n=74), respectively (Prod Info SPRYCEL(R) oral tablets, 2015).

a) During clinical trials, myalgia (all grades) was reported in 7% of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).
b) In clinical trials of chronic myeloid leukemia (CML) patients with prior imatinib resistance or intolerance, myalgia (all grades) occurred in 13% of chronic phase CML patients (n=165) treated with dasatinib 100 mg once daily (Prod Info SPRYCEL(R) oral tablets, 2015).

a) During clinical trials, arthralgia (all grades) was reported in 7% of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).
b) In clinical trials of chronic myeloid leukemia (CML) patients with prior imatinib resistance or intolerance, arthralgia (all grades) occurred in 13% of chronic phase CML patients (n=165) treated with dasatinib 100 mg once daily. Among patients with advanced phase CML treated with dasatinib 140 mg once daily, arthralgia (all grades) occurred in 10% and 5% of those in the accelerated phase (n=157) or myeloid blast phase (n=74), respectively (Prod Info SPRYCEL(R) oral tablets, 2015).

a) During clinical trials, muscle spasms (all grades) were reported in 5% of 258 patients with newly diagnosed chronic phase chronic myeloid leukemia who were treated with dasatinib (Prod Info SPRYCEL(R) oral tablets, 2015).

a) In clinical trials of chronic myeloid leukemia (CML) patients with prior imatinib resistance or intolerance, infections (all grades), including bacterial, viral, fungal, and non-specified, and grade 3 or 4 infections occurred in 13% and 1% of chronic phase CML patients (n=165) treated with dasatinib 100 mg once daily, respectively. Among patients with advanced phase CML treated with dasatinib 140 mg once daily, infections (all grades) occurred in 10%, 14%, and 9% of those in the accelerated phase (n=157), myeloid blast phase (n=74), or lymphoid blast phase (n=33), respectively. Grade 3 or 4 infections occurred in 6%, 7%, and 0% of these patients, respectively (Prod Info SPRYCEL(R) oral tablets, 2015).

a) CASE REPORT: A 74-year-old woman developed systemic lupus erythematosus after receiving dasatinib for the treatment of chronic phase chronic myelogenous leukemia (CML). The patient received dasatinib 50 mg orally twice daily after failing to achieve a cytogenetic response with imatinib 800 mg/day. Although the patient achieved a complete hematologic response with dasatinib, she developed fatigue and arthralgia after 3 months of therapy and fever, weight loss, dry cough, and shortness of breath after 6 months of therapy. On physical exam, the patient had mild hepatosplenomegaly; additionally, she had bilateral pleural effusions (confirmed by CT scan), a pericardial effusion (on cardiac ultrasonography), and an elevated C-reactive protein concentration (62 mg/L). Immunological tests revealed the presence of antinuclear (ANA) and anti-DNA antibodies. Antihistone antibodies, as well as other autoantibodies (rheumatoid factor, anticardiolipin, and antibodies to soluble nuclear antigens), were not present. The patient discontinued dasatinib after 9 months of therapy and her symptoms fully resolved within 1 month. After dasatinib was discontinued, DNA antibodies disappeared within 2 months and ANA were undetectable after 8 months. The patient experienced a hematologic CML relapse and was subsequently treated with hydroxyurea followed by nilotinib therapy (Rea et al, 2008).

a) It is unknown whether dasatinib is excreted in human breast milk. Due to the potential risk for adverse effects in the nursing infant, do not breastfeed during treatment and for at least 2 weeks after discontinuation (Prod Info SPRYCEL(R) oral tablets, 2015a).

a) Monitor ECG for evidence of QT prolongation.

a) Monitor vital signs.
b) Monitor for clinical evidence of infection, with particular attention to: odontogenic infection, oropharynx, esophagus, soft tissues particularly in the perirectal region, exit and tunnel sites of central venous access devices, upper and lower respiratory tracts, and urinary tract.
c) Evaluate patients for signs and symptoms of mucositis.

a) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
b) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).

a) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

a) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
b) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

a) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

a) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
b) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

a) Treatment is symptomatic and supportive. Treat persistent nausea and vomiting with several antiemetics of different classes. Administer colony stimulating factors (filgrastim or sargramostim) as these patients are at risk for severe neutropenia.

a) Treatment is symptomatic and supportive. Administer colony stimulating factors (filgrastim or sargramostim) as these patients are at risk for severe neutropenia. Transfusion of platelets and/or packed red cells may be needed in patients with severe thrombocytopenia, anemia, or hemorrhage. Severe nausea and vomiting may respond to a combination of agents from different drug classes. Monitor for fluid retention following a significant exposure; monitor fluid and electrolyte balance frequently. Evaluate and monitor airway patency and adequacy of respiration and oxygenation. Treatment may consist of diuretic therapy to manage fluid retention and an increase in plasma volume. If symptoms are severe, endotracheal intubation and assisted ventilation may be indicated. Therapeutic doses of dasatinib may cause prolongation of the QT interval. In patients with QT prolongation, monitor serum electrolytes including potassium, calcium and magnesium in patients with significant overdose; correct any abnormalities. At the time of this review, torsades de pointes has not been reported with therapy.

a) DOSING

a) Higher doses of filgrastim, such as those used for bone marrow transplant, may be indicated after overdose.
b) FILGRASTIM: In patients receiving bone marrow transplant (BMT), the recommended dose of filgrastim is 10 mcg/kg/day given as an IV infusion no longer than 24 hours. The daily dose of filgrastim should be titrated based on neutrophil response (ie, absolute neutrophil count (ANC)) as follows (Prod Info NEUPOGEN(R) subcutaneous injection, intravenous injection, 2015):
c) In BMT studies, patients received up to 138 mcg/kg/day without toxic effects. However, a flattening of the dose response curve occurred at daily doses of greater than 10 mcg/kg/day (Prod Info NEUPOGEN(R) subcutaneous injection, intravenous injection, 2015).
d) SARGRAMOSTIM: This agent has been indicated for the acceleration of myeloid recovery in patients after autologous or allogenic BMT. Usual dosing is 250 mcg/m(2)/day as a 2-hour IV infusion over a 2-hour period. Duration is based on neutrophil recovery (Prod Info LEUKINE(R) subcutaneous injection liquid, intravenous injection liquid, subcutaneous injection lyophilized powder for solution, intravenous injection lyophilized powder for solution, 2013).

a) In pediatric patients, the use of colony stimulating factors (CSFs) can reduce the risk of febrile neutropenia. However, this therapy should be limited to patients at high risk due to the potential of developing a secondary myeloid leukemia or myelodysplastic syndrome associated with the use of CSFs. Careful consideration is suggested in using CSFs in children with acute lymphocytic leukemia (ALL) (Smith et al, 2006).

a) Treat high risk patients with fluoroquinolone prophylaxis, if the patient is expected to have prolonged (more than 7 days), profound neutropenia (ANC 100 cells/mm(3) or less). This has been shown to decrease the relative risk of all cause mortality by 48% and or infection-related mortality by 62% in these patients (most patients in these studies had hematologic malignancies or received hematopoietic stem cell transplant). Low risk patients usually do not routinely require antibacterial prophylaxis (Freifeld et al, 2011).

a) Due to the risk of potentially severe neutropenia following overdose with dasatinib, all patients should be monitored for the development of febrile neutropenia.

a) SUMMARY: The following are guidelines presented by the Infectious Disease Society of America (IDSA) to manage patients with cancer that may develop chemotherapy-induced fever and neutropenia (Freifeld et al, 2011).
b) DEFINITION: Patients who present with fever and neutropenia should be treated immediately with empiric antibiotic therapy; antibiotic therapy should broadly treat both gram-positive and gram-negative pathogens (Freifeld et al, 2011).
c) CRITERIA: Fever (greater than or equal to 38.3 degrees C) AND neutropenia (an absolute neutrophil count (ANC) of less than or equal to 500 cells/mm(3)). Profound neutropenia has been described as an ANC of less than or equal to 100 cells/mm(3) (Freifeld et al, 2011).
d) ASSESSMENT: HIGH RISK PATIENT: Anticipated neutropenia of greater than 7 days, clinically unstable and significant comorbidities (ie, new onset of hypotension, pneumonia, abdominal pain, neurologic changes). LOW RISK PATIENT: Neutropenia anticipated to last less than 7 days, clinically stable with no comorbidities (Freifeld et al, 2011).
e) LABORATORY ANALYSIS: CBC with differential leukocyte count and platelet count, hepatic and renal function, electrolytes, 2 sets of blood cultures with a least a set from a central and/or peripheral indwelling catheter site, if present. Urinalysis and urine culture (if urinalysis positive, urinary symptoms or indwelling urinary catheter). Chest x-ray, if patient has respiratory symptoms (Freifeld et al, 2011).
f) EMPIRIC ANTIBIOTIC THERAPY: HIGH RISK patients should be admitted to the hospital for IV therapy. Any of the following can be used for empiric antibiotic monotherapy: piperacillin-tazobactam; a carbapenem (meropenem or imipenem-cilastatin); an antipseudomonal beta-lactam agent (eg, ceftazidime or cefepime). LOW RISK patients should be placed on an oral empiric antibiotic therapy (ie, ciprofloxacin plus amoxicillin-clavulanate), if able to tolerate oral therapy and observed for 4 to 24 hours. IV therapy may be indicated, if patient poorly tolerating an oral regimen (Freifeld et al, 2011).
g) COMMON PATHOGENS frequently observed in neutropenic patients (Freifeld et al, 2011):
h) HEMATOPOIETIC GROWTH FACTORS (G-CSF or GM-CSF): Prophylactic use of these agents should be considered in patients with an anticipated risk of fever and neutropenia of 20% or greater. In general, colony stimulating factors are not recommended for the treatment of established fever and neutropenia (Freifeld et al, 2011).

a) Treat patients with high-dose dopamine (D2) receptor antagonists (eg, metoclopramide), phenothiazines (eg, prochlorperazine, promethazine), 5-HT3 serotonin antagonists (eg, dolasetron, granisetron, ondansetron), benzodiazepines (eg, lorazepam), corticosteroids (eg, dexamethasone), and antipsychotics (eg, haloperidol, olanzapine); diphenhydramine may be required to prevent dystonic reactions from dopamine antagonists, phenothiazines, and antipsychotics. It may be necessary to treat with multiple concomitant agents, from different drug classes, using alternating schedules or alternating routes. In general, rectal medications should be avoided in patients with neutropenia.
b) DOPAMINE RECEPTOR ANTAGONISTS: Metoclopramide: Adult: 10 to 40 mg orally or IV and then every 4 or 6 hours, as needed. Dose of 2 mg/kg IV every 2 to 4 hours for 2 to 5 doses may also be given. Monitor for dystonic reactions; add diphenhydramine 25 to 50 mg orally or IV every 4 to 6 hours as needed for dystonic reactions (None Listed, 1999). Children: 0.1 to 0.2 mg/kg IV every 6 hours; MAX 10 mg/dose (Dupuis & Nathan, 2003).
c) PHENOTHIAZINES: Prochlorperazine: Adult: 25 mg suppository as needed every 12 hours or 10 mg orally every 4 or 6 hours as needed. IV dose: 2.5 to 10 mg by slow IV injection or infusion not to exceed 5 mg per minute (MAX 40 mg/day); Children (2 yrs or older): 20 to 29 pounds: 2.5 mg orally 1 to 2 times daily (MAX 7.5 mg/day); 30 to 39 pounds: 2.5 mg orally 2 to 3 times daily (MAX 10 mg/day); 40 to 85 pounds: 2.5 mg orally 3 times daily or 5 mg orally twice daily (MAX 15 mg/day) OR 2 yrs or older and greater than 20 pounds: 0.06 mg/pound IM as a single dose (Prod Info COMPAZINE(R) oral tablets, 2013; Prod Info prochlorperazine edisylate intramuscular intravenous injection, 2011; Prod Info COMPAZINE(R) rectal suppositories, 2013). Promethazine: Adult: 12.5 to 25 mg orally or IV every 4 to 6 hours; Children (2 yr and older) 12.5 to 25 mg OR 0.5 mg/pound orally every 4 to 6 hours as needed. Monitor children closely for respiratory depression or apnea (Prod Info promethazine HCl oral tablets, 2013). Chlorpromazine: Children: Greater than 6 months of age, 0.55 mg/kg orally every 4 to 6 hours, or IV every 6 to 8 hours; max of 40 mg per dose if age is less than 5 years or weight is less than 22 kg (None Listed, 1999).
d) SEROTONIN 5-HT3 ANTAGONISTS: The following antiemetic dosing is based on high emetic risk. Dolasetron: Adult: 100 mg orally ONLY. Granisetron: Adult: 2 mg orally daily or 1 mg or 0.01 mg/kg (maximum 1 mg) IV. Ondansetron: Adult: 8 mg orally twice daily; 8 mg or 0.15 mg/kg IV. Palonosetron: Adult: 0.5 mg oral; 0.25 mg IV. Tropisetron: Adult: 5 mg oral; 5 mg IV. Ramosetron: 0.3 mg IV (Basch et al, 2011); Ondansetron: Children (older than 3 years of age): 0.15 mg/kg IV 4 and 8 hours after chemotherapy (None Listed, 1999).
e) BENZODIAZEPINES: Lorazepam: Adult: 1 to 2 mg orally or IM/IV every 6 hours; Children: 0.05 mg/kg, up to a maximum of 3 mg, orally or IV every 8 to 12 hours as needed (None Listed, 1999).
f) STEROIDS: Dexamethasone: Adult: 10 to 20 mg orally or IV every 4 to 6 hours; Children: 5 to 10 mg/m(2) orally or IV every 12 hours as needed; methylprednisolone: children: 0.5 to 1 mg/kg orally or IV every 12 hours as needed (None Listed, 1999).
g) ANTIPSYCHOTICS: Haloperidol: Adult: 1 to 4 mg orally or IM/IV every 6 hours as needed (None Listed, 1999).

a) Withdraw the causative agent. Hemodynamically unstable patients with Torsades de pointes (TdP) require electrical cardioversion. Emergent treatment with magnesium (first-line agent) or atrial overdrive pacing is indicated. Detect and correct underlying electrolyte abnormalities (ie, hypomagnesemia, hypokalemia, hypocalcemia). Correct hypoxia, if present (Drew et al, 2010; Neumar et al, 2010; Keren et al, 1981; Smith & Gallagher, 1980).
b) Polymorphic VT associated with acquired long QT syndrome may be treated with IV magnesium. Overdrive pacing or isoproterenol may be successful in terminating TdP, particularly when accompanied by bradycardia or if TdP appears to be precipitated by pauses in rhythm (Neumar et al, 2010). In patients with polymorphic VT with a normal QT interval, magnesium is unlikely to be effective (Link et al, 2015).

a) Magnesium is recommended (first-line agent) for the prevention and treatment of drug-induced torsades de pointes (TdP) even if the serum magnesium concentration is normal. QTc intervals greater than 500 milliseconds after a potential drug overdose may correlate with the development of TdP (Charlton et al, 2010; Drew et al, 2010). ADULT DOSE: No clearly established guidelines exist; an optimal dosing regimen has not been established. Administer 1 to 2 grams diluted in 10 milliliters D5W IV/IO over 15 minutes (Neumar et al, 2010). Followed if needed by a second 2 gram bolus and an infusion of 0.5 to 1 gram (4 to 8 mEq) per hour in patients not responding to the initial bolus or with recurrence of dysrhythmias (American Heart Association, 2005; Perticone et al, 1997). Rate of infusion may be increased if dysrhythmias recur. For persistent refractory dysrhythmias, a continuous infusion of up to 3 to 10 milligrams/minute in adults may be given (Charlton et al, 2010).
b) PEDIATRIC DOSE: 25 to 50 milligrams/kilogram diluted to 10 milligrams/milliliter for intravenous infusion over 5 to 15 minutes up to 2 g (Charlton et al, 2010).
c) PRECAUTIONS: Use with caution in patients with renal insufficiency.
d) MAJOR ADVERSE EFFECTS: High doses may cause hypotension, respiratory depression, and CNS toxicity (Neumar et al, 2010). Toxicity may be observed at magnesium levels of 3.5 to 4.0 mEq/L or greater (Charlton et al, 2010).
e) MONITORING PARAMETERS: Monitor heart rate and rhythm, blood pressure, respiratory rate, motor strength, deep tendon reflexes, serum magnesium, phosphorus, and calcium concentrations (Prod Info magnesium sulfate heptahydrate IV, IM injection, solution, 2009).

a) Institute electrical overdrive pacing at a rate of 130 to 150 beats per minute, and decrease as tolerated. Rates of 100 to 120 beats per minute may terminate torsades (American Heart Association, 2005). Pacing can be used to suppress self-limited runs of TdP that may progress to unstable or refractory TdP, or for override refractory, persistent TdP before the potential development of ventricular fibrillation (Charlton et al, 2010). In a case series overdrive pacing was successful in terminating TdP associated with bradycardia and drug-induced QT prolongation (Neumar et al, 2010).

a) Potassium supplementation, even if serum potassium is normal, has been recommended by many experts (Charlton et al, 2010; American Heart Association, 2005). Supplementation to supratherapeutic potassium concentrations of 4.5 to 5 mmol/L has been suggested, although there is little evidence to determine the optimal range in dysrhythmia (Drew et al, 2010; Charlton et al, 2010).

a) Isoproterenol has been successful in aborting torsades de pointes that was resistant to magnesium therapy in a patient in whom transvenous overdrive pacing was not an option (Charlton et al, 2010) and has been successfully used to treat torsades de pointes associated with bradycardia and drug induced QT prolongation (Keren et al, 1981; Neumar et al, 2010). Isoproterenol may have a limited role in pharmacologic overdrive pacing in select patients with drug-induced torsades de pointes and acquired long QT syndrome (Charlton et al, 2010; Neumar et al, 2010). Isoproterenol should be avoided in patients with polymorphic VT associated with familial long QT syndrome (Neumar et al, 2010).
b) DOSE: ADULT: 2 to 10 micrograms/minute via a continuous monitored intravenous infusion; titrate to heart rate and rhythm response (Neumar et al, 2010).
c) PRECAUTIONS: Correct hypovolemia before using; contraindicated in patients with acute cardiac ischemia (Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).
d) MAJOR ADVERSE EFFECTS: Tachycardia, cardiac dysrhythmias, palpitations, hypotension or hypertension, nervousness, headache, dizziness, and dyspnea (Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).
e) MONITORING PARAMETERS: Monitor heart rate and rhythm, blood pressure, respirations and central venous pressure to guide volume replacement (Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).

a) Mexiletine, verapamil, propranolol, and labetalol have also been used to treat TdP, but results have been inconsistent (Khan & Gowda, 2004).

a) Avoid class Ia antidysrhythmics (eg, quinidine, disopyramide, procainamide, aprindine), class Ic (eg, flecainide, encainide, propafenone) and most class III antidysrhythmics (eg, N-acetylprocainamide, sotalol) since they may further prolong the QT interval and have been associated with TdP.

a) Recommended dose is 100 mg orally once daily (Prod Info SPRYCEL(R) oral tablets, 2014).

a) Recommended dose is 140 mg orally once daily (Prod Info SPRYCEL(R) oral tablets, 2014).