6.1 Chronic Myeloid Leukemia
The majority of Gleevec-treated patients experienced adverse reactions at some time. Most reactions were of mild-to-moderate grade, but drug was discontinued for drug-related adverse reactions in 2.4% of newly diagnosed patients, 4% of patients in chronic phase after failure of interferon-alpha therapy, 4% in accelerated phase and 5% in blast crisis.

The most frequently reported drug-related adverse reactions were edema, nausea and vomiting, muscle cramps, musculoskeletal pain, diarrhea and rash (Table 2 for newly diagnosed CML, Table 3 for other CML patients). Edema was most frequently periorbital or in lower limbs and was managed with diuretics, other supportive measures, or by reducing the dose of Gleevec. [see Dosage and Administration (2.10)]. The frequency of severe superficial edema was 1.5%-6%.

A variety of adverse reactions represent local or general fluid retention including pleural effusion, ascites, pulmonary edema and rapid weight gain with or without superficial edema. These reactions appear to be dose related, were more common in the blast crisis and accelerated phase studies (where the dose was 600 mg/day), and are more common in the elderly. These reactions were usually managed by interrupting Gleevec treatment and using diuretics or other appropriate supportive care measures. A few of these reactions may be serious or life threatening, and one patient with blast crisis died with pleural effusion, congestive heart failure, and renal failure.

Adverse reactions, regardless of relationship to study drug, that were reported in at least 10% of the Gleevec treated patients are shown in Tables 2 and 3.

Table 2 Adverse Reactions Reported in Newly Diagnosed CML Clinical Trial (≥10% of Gleevec Treated Patients)(1)  All Grades CTC Grades 3/4
 Gleevec IFN+Ara−C Gleevec IFN+Ara−C
Preferred Term N=551 (%) N=533 (%) N=551 (%) N=533 (%)
Fluid Retention 61.7 11.1 2.5 0.9
− Superficial Edema 59.9 9.6 1.5 0.4
− Other Fluid Retention Reactions2 6.9 1.9 1.3 0.6
Nausea 49.5 61.5 1.3 5.1
Muscle Cramps 49.2 11.8 2.2 0.2
Musculoskeletal Pain 47.0 44.8 5.4 8.6
Diarrhea 45.4 43.3 3.3 3.2
Rash and Related Terms 40.1 26.1 2.9 2.4
Fatigue 38.8 67.0 1.8 25.1
Headache 37.0 43.3 0.5 3.8
Joint Pain 31.4 38.1 2.5 7.7
Abdominal Pain 36.5 25.9 4.2 3.9
Nasopharyngitis 30.5 8.8 0 0.4
Hemorrhage 28.9 21.2 1.8 1.7
- GI Hemorrhage 1.6 1.1 0.5 0.2
- CNS Hemorrhage 0.2 0.4 0 0.4
Myalgia 24.1 38.8 1.5 8.3
Vomiting 22.5 27.8 2.0 3.4
Dyspepsia 18.9 8.3 0 0.8
Cough 20.0 23.1 0.2 0.6
Pharyngolaryngeal Pain 18.1 11.4 0.2 0
Upper Respiratory Tract Infection 21.2 8.4 0.2 0.4
Dizziness 19.4 24.4 0.9 3.8
Pyrexia 17.8 42.6 0.9 3.0
Weight Increased 15.6 2.6 2.0 0.4
Insomnia 14.7 18.6 0 2.3
Depression 14.9 35.8 0.5 13.1
Influenza 13.8 6.2 0.2 0.2
Bone Pain 11.3 15.6 1.6 3.4
Constipation 11.4 14.4 0.7 0.2
Sinusitis 11.4 6.0 0.2 0.2
(1)All adverse reactions occurring in ≥10% of Gleevec treated patients are listed regardless of suspected relationship to treatment.
(2)Other fluid retention reactions include pleural effusion, ascites, pulmonary edema, pericardial effusion, anasarca, edema aggravated, and fluid retention not otherwise s