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Side Effects > Gleevec

Gleevec Side Effects

Generic Name: Imatinib

Please note - some side effects for Gleevec may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).


For the consumer

For the professional

Side Effects of Gleevec - for the consumer


Gleevec

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Gleevec:

Anxiety; constipation; cough; diarrhea; dizziness; gas; headache; increased tear production; loss of appetite; muscle cramps; nausea; night sweats; nose and throat irritation; stomach pain or upset; taste changes; tiredness; trouble sleeping; vomiting; weakness.

Seek medical attention right away if any of these SEVERE side effects occur when using Gleevec:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); black or bloody stools; blistered, peeling, reddened, scaling, or swollen skin; bone pain; change in the amount of urine produced; chest pain; chills, fever, or sore throat; confusion; dark urine; depression; fast or irregular heartbeat; joint or muscle pain; severe or persistent headache; severe stomach pain; severe tiredness or weakness; shortness of breath; slurred speech; sudden unusual weight gain; swelling of the hands, feet, ankles, or around the eyes; unusual bruising or bleeding; vision problems; vomit that looks like coffee grounds; yellowing of the eyes or skin.

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For the professional


Gleevec

Chronic Myeloid Leukemia

The majority of Gleevec-treated patients experienced adverse events at some time. Most events were of mild-to-moderate grade, but drug was discontinued for drug-related adverse events in 3.1% 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 events were edema, nausea and vomiting, muscle cramps, musculoskeletal pain, diarrhea and rash (Table 5 for newly diagnosed CML, Table 6 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® (imatinib mesylate). The frequency of severe superficial edema was 1.1%-6%.

      A variety of adverse events represent local or general fluid retention including pleural effusion, ascites, pulmonary edema and rapid weight gain with or without superficial edema. These events 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 events were usually managed by interrupting Gleevec treatment and with diuretics or other appropriate supportive care measures. However, a few of these events may be serious or life threatening, and one patient with blast crisis died with pleural effusion, congestive heart failure, and renal failure.

      Adverse events, regardless of relationship to study drug, that were reported in at least 10% of the patients treated in the Gleevec studies are shown in Tables 5 and 6.

Table 5      Adverse Experiences Reported in Newly Diagnosed CML Clinical Trial (≥10% of all 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 59.2 10.7 1.8 0.9
     − Superficial Edema 57.5 9.2 1.1 0.4
     − Other Fluid
      Retention Events 6.9 1.9 0.7 0.6
Nausea 47 61.5 0.9 5.1
Muscle Cramps 43.2 11.4 1.6 0.2
Musculoskeletal Pain 39.2 44.1 3.4 8.1
Diarrhea 38.5 42 2.0 3.2
Rash and Related Terms 37.2 25.7 2.4 2.4
Fatigue 37.0 66.8 1.6 25.0
Headache 33.6 43.3 0.5 3.6
Joint Pain 30.3 39.4 2.5 7.3
Abdominal Pain 29.9 25.0 2.5 3.9
Nasopharyngitis 26.9 8.4 0 0.2
Hemorrhage 24.1 20.8 1.1 1.5
      - GI Hemorrhage 1.3 1.1 0.5 0.2
      - CNS Hemorrhage 0.2 0.2 0 0.2
Myalgia 22.5 38.8 1.5 8.1
Vomiting 20.5 27.4 1.5 3.4
Dyspepsia 17.8 9.2 0 0.8
Cough 17.4 23.1 0.2 0.6
Pharyngolaryngeal Pain 16.9 11.3 0.2 0
Upper Repiratory Tract Infection 16.5 8.4 0.2 0.4
Dizziness 15.8 24.2 0.9 3.6
Pyrexia 15.4 42.4 0.9 3.0
Weight Increased 15.2 2.1 1.6 0.4
Insomnia 13.2 18.8 0 2.3
Depression 12.7 35.8 0.5 13.1
Influenza 11.1 6.0 0.2 0.2

(1)      All adverse events occurring in ≥10% of patients are listed regardless of suspected relationship to treatment.

Table 6      Adverse Experiences Reported in Other CML Clinical Trials (≥10% of all patients in any trial)(1)
Myeloid Blast Accelerated Chronic Phase,
Crisis Phase IFN Failure
(n= 260) (n=235) (n=532)
% % %
All Grade All Grade All Grade
Preferred Term Grades 3/4 Grades 3/4 Grades 3/4
Fluid Retention 72 11 76 6 69 4
      - Superficial Edema 66 6 74 3 67 2
      - Other Fluid Retention Events(2) 22 6 15 4 7 2
Nausea 71 5 73 5 63 3
Muscle Cramps 28 1 47 0.4 62 2
Vomiting 54 4 58 3 36 2
Diarrhea 43 4 57 5 48 3
Hemorrhage 53 19 49 11 30 2
      - CNS Hemorrhage 9 7 3 3 2 1
      - GI Hemorrhage 8 4 6 5 2 0.4
Musculoskeletal Pain 42 9 49 9 38 2
Fatigue 30 4 46 4 48 1
Skin Rash 36 5 47 5 47 3
Pyrexia 41 7 41 8 21 2
Arthralgia 25 5 34 6 40 1
Headache 27 5 32 2 36 0.6
Abdominal Pain 30 6 33 4 32 1
Weight Increased 5 1 17 5 32 7
Cough 14 0.8 27 0.9 20 0
Dyspepsia 12 0 22 0 27 0
Myalgia 9 0 24 2 27 0.2
Nasopharyngitis 10 0 17 0 22 0.2
Asthenia 18 5 21 5 15 0.2
Dyspnea 15 4 21 7 12 0.9
Upper Respiratory Tract Infection 3 0 12 0.4 19 0
Anorexia 14 2 17 2 7 0
Night Sweats 13 0.8 17 1 14 0.2
Constipation 16 2 16 0.9 9 0.4
Dizziness 12 0.4 13 0 16 0.2
Pharyngitis 10 0 12 0 15 0
Insomnia 10 0 14 0 14 0.2
Pruritus 8 1 14 0.9 14 0.8
Hypokalemia 13 4 9 2 6 0.8
Pneumonia 13 7 10 7 4 1
Anxiety 8 0.8 12 0 8 0.4
Liver Toxicity 10 5 12 6 6 3
Rigors 10 0 12 0.4 10 0
Chest Pain 7 2 10 0.4 11 0.8
Influenza 0.8 0.4 6 0 11 0.2
Sinusitis 4 0.4 11 0.4 9 0.4

(1)      All adverse events occurring in ≥10% of patients are listed regardless of suspected relationship to treatment.

(2)      Other fluid retention events include pleural effusion, ascites, pulmonary edema, pericardial effusion, anasarca, edema aggravated, and fluid retention not otherwise specified.


Hematologic Toxicity

Cytopenias, and particularly neutropenia and thrombocytopenia, were a consistent finding in all studies, with a higher frequency at doses ≥750 mg (Phase 1 study). However, the occurrence of cytopenias in CML patients was also dependent on the stage of the disease.

      In patients with newly diagnosed CML, cytopenias were less frequent than in the other CML patients. The frequency of grade 3 or 4 neutropenia and thrombocytopenia was between 2- and 3-fold higher in blast crisis and accelerated phase compared to chronic phase. The median duration of the neutropenic and thrombocytopenic episodes varied from 2 to 3 weeks, and from 2 to 4 weeks, respectively.

      These events can usually be managed with either a reduction of the dose or an interruption of treatment with Gleevec, but in rare cases require permanent discontinuation of treatment.

Hepatotoxicity

Severe elevation of transaminases or bilirubin occurred in 3%-6% and were usually managed with dose reduction or interruption (the median duration of these episodes was approximately 1 week). Treatment was discontinued permanently because of liver laboratory abnormalities in less than 0.5% of CML patients. However, one patient, who was taking acetaminophen regularly for fever, died of acute liver failure. In the GIST trial, grade 3 or 4 SGPT (ALT) elevations were observed in 6.8% of patients and grade 3 or 4 SGOT (AST) elevations were observed in 4.8% of patients. Bilirubin elevation was observed in 2.7% of patients.

Adverse Reactions in Pediatric Population

The overall safety profile of pediatric patients treated with Gleevec in 39 children studied was similar to that found in studies with adult patients, except that musculoskeletal pain was less frequent (20.5%) and peripheral edema was not reported.

Adverse Effects in Other Subpopulations

In older patients (≥65 years old), with the exception of edema, where it was more frequent, there was no evidence of an increase in the incidence or severity of adverse events. In women there was an increase in the frequency of neutropenia, as well as Grade 1/2 superficial edema, headache, nausea, rigors, vomiting, rash, and fatigue. No differences were seen related to race but the subsets were too small for proper evaluation.

Table 7      Lab Abnormalities in Newly Diagnosed CML Trial
Gleevec® IFN+Ara−C
N=551 N=533
% %
CTC Grades Grade 3 Grade 4 Grade 3 Grade 4
Hematology Parameters
     − Neutropenia* 12.3 3.1 20.8 4.3
     − Thrombocytopenia* 8.3 0.2 15.9 0.6
     − Anemia 3.1 0.9 4.1 0.2
Biochemistry Parameters
     − Elevated Creatinine 0 0 0.4 0
     − Elevated Bilirubin 0.7 0.2 0.2 0
     − Elevated Alkaline
      Phosphatase
0.2 0 0.8 0
     − Elevated SGOT (AST) 2.9 0.2 3.8 0.4
     − Elevated SGPT (ALT) 3.1 0.4 5.6 0

*p<0.001 (difference in Grade 3 plus 4 abnormalities between the two treatment groups)

Table 8      Lab Abnormalities in Other CML Clinical Trials
Myeloid Blast Accelerated Chronic Phase,
Crisis Phase IFN Failure
(n=260) (n=235) (n=532)
600 mg n=223 600 mg n=158
400 mg n=37 400 mg n=77 400 mg
% % %
Grade Grade Grade Grade Grade Grade
CTC Grades 3 4 3 4 3 4
Hematology Parameters
     − Neutropenia 16 48 23 36 27 9
     − Thrombocytopenia 30 33 31 13 21 <1
     − Anemia 42 11 34 7 6 1
Biochemistry Parameters
     − Elevated Creatinine 1.5 0 1.3 0 0.2 0
     − Elevated Bilirubin 3.8 0 2.1 0 0.6 0
     − Elevated Alkaline
      Phosphatase
4.6 0 5.5 0.4 0.2 0
     − Elevated SGOT (AST) 1.9 0 3.0 0 2.3 0
     − Elevated SGPT (ALT) 2.3 0.4 4.3 0 2.1 0

CTC Grades: neutropenia (Grade 3 ≥0.5-1.0 x 109/L, Grade 4 <0.5 x 109/L), thrombocytopenia (Grade 3 ≥10-50 x 109/L, Grade 4 <10 x 109/L), anemia (hemoglobin ≥65-80 g/L, Grade 4 <65 g/L), elevated creatinine (Grade 3 >3-6 x upper limit normal range [ULN], Grade 4 >6 x ULN), elevated bilirubin (Grade 3 >3-10 x ULN, Grade 4 >10 x ULN), elevated alkaline phosphatase (Grade 3 >5-20 x ULN, Grade 4 >20 x ULN), elevated SGOT or SGPT (Grade 3 >5-20 x ULN, Grade 4 >20 x ULN)

     

Gastrointestinal Stromal Tumors

The majority of Gleevec-treated patients experienced adverse events at some time. The most frequently reported adverse events were edema, nausea, diarrhea, abdominal pain, muscle cramps, fatigue, and rash. Most events were of mild-to-moderate severity. Drug was discontinued for adverse events in 7 patients (5%) in both dose levels studied. Superficial edema, most frequently periorbital or lower extremity edema, was managed with diuretics, other supportive measures, or by reducing the dose of Gleevec® (imatinib mesylate). Severe (CTC Grade 3/4) superficial edema was observed in 3 patients (2%), including face edema in one patient. Grade 3/4 pleural effusion or ascites was observed in 3 patients (2%).

      Adverse events, regardless of relationship to study drug, that were reported in at least 10% of the patients treated with Gleevec are shown in Table 9. No major differences were seen in the severity of adverse events between the 400-mg or 600-mg treatment groups, although overall incidence of diarrhea, muscle cramps, headache, dermatitis, and edema was somewhat higher in the 600-mg treatment group.

     

Table 9      Adverse Experiences Reported in GIST Trial (≥10% of all patients at either dose)(1)
All CTC Grades
Initial dose (mg/day)
CTC Grade 3/4
Initial dose (mg/day)
400 mg
(n=73)
600 mg
(n=74)
400 mg
(n=73)
600 mg
(n=74)
Preferred Term % % % %
Fluid Retention 81 80 7 12
- Superficial Edema 81 77 6 5
- Pleural Effusion or Ascites 15 12 3 8
Diarrhea 59 70 3 7
Nausea 63 74 6 4
Fatigue 48 53 1 1
Muscle Cramps 47 58 0 0
Abdominal Pain 40 37 11 4
Rash and Related Terms 38 53 4 3
Vomiting 38 35 3 5
Musculoskeletal Pain 37 30 6 1
Headache 33 39 0 0
Flatulence 30 34 0 0
Any Hemorrhage 26 34 6 11
- Tumor Hemorrhage 1 4 1 4
- Cerebral Hemorrhage 1 0 1 0
- GI Tract Hemorrhage 4 4 4 3
- Other Hemorrhage(2) 22 27 0 5
Pyrexia 25 16 3 0
Back Pain 23 26 6 0
Nasopharyngitis 21 27 0 0
Insomnia 19 18 1 0
Lacrimation Increased 16 18 0 0
Dyspepsia 15 15 0 0
Upper Respiratory Tract Infection 14 18 0 0
Liver Toxicity 12 12 6 8
Dizziness 12 11 0 0
Loose Stools 12 10 0 0
Operation 12 8 6 4
Pharyngolaryngeal Pain 12 7 0 0
Joint Pain 11 15 1 0
Constipation 11 10 0 1
Anxiety 11 7 0 0
Taste Disturbance 3 15 0 0
  1. All adverse events occurring in ≥10% of patients are listed regardless of suspected relationship to treatment.
  2. This category includes conjunctival hemorrhage, blood in stool, epistaxis, hematuria, post-procedural hemorrhage, bruising, and contusion.

      Clinically relevant or severe abnormalities of routine hematologic or biochemistry laboratory values are presented in Table 10.

Table 10      Laboratory Abnormalities in GIST Trial
400 mg 600 mg
(n=73) (n=74)
% %
CTC Grades Grade 3 Grade 4 Grade 3 Grade 4
Hematology Parameters
     − Anemia 3 0 8 1
     − Thrombocytopenia 0 0 1 0
     − Neutropenia 7 3 8 3
Biochemistry Parameters
     − Elevated Creatinine 0 0 3 0
     − Reduced Albumin 3 0 4 0
     − Elevated Bilirubin 1 0 1 3
     − Elevated Alkaline Phosphatase 0 0 3 0
     − Elevated SGOT (AST) 4 0 3 3
     − Elevated SGPT (ALT) 6 0 7 1

CTC Grades: neutropenia (Grade 3 ≥0.5-1.0 x 109/L, Grade 4 <0.5 x 109/L), thrombocytopenia (Grade 3 ≥10 - 50 x 109/L, Grade 4 <10 x 109/L), anemia (Grade 3 ≥65-80 g/L, grade 4 <65 g/L), elevated creatinine (Grade 3 >3-6 x upper limit normal range [ULN], Grade 4 >6 x ULN), elevated bilirubin (Grade 3 >3-10 x ULN, Grade 4 >10 x ULN), elevated alkaline phosphatase, SGOT or SGPT (Grade 3 >5-20 x ULN, Grade 4 >20 x ULN), albumin (Grade 3 <20 g/L)

Additional Data From Multiple Clinical Trials

The following less common (estimated 1%-10%), infrequent (estimated 0.1%-1%), and rare (estimated less than 0.1%) adverse events have been reported during clinical trials of Gleevec. These events are included based on clinical relevance.

Cardiovascular: Infrequent: cardiac failure, tachycardia, hypertension, hypotension, flushing, peripheral coldness

Rare: pericarditis

Clinical Laboratory Tests: Infrequent: blood CPK increased, blood LDH increased

Dermatologic: Less common: dry skin, alopecia

Infrequent: exfoliative dermatitis, bullous eruption, nail disorder, skin pigmentation changes, photosensitivity reaction, purpura, psoriasis

Rare: vesicular rash, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, acute febrile neutrophilic dermatosis (Sweet’s syndrome)

Digestive: Less common: abdominal distention, gastroesophageal reflux, mouth ulceration Infrequent: gastric ulcer, gastroenteritis, gastritis

Rare: colitis, ileus/intestinal obstruction, pancreatitis, diverticulitis, tumor hemorrhage/tumor necrosis, gastrointestinal perforation

General Disorders and Administration Site Conditions: Rare: tumor necrosis

Hematologic: Infrequent: pancytopenia

Rare: aplastic anemia 

Hepatobiliary: Uncommon: hepatitis

rare: hepatic failure

Hypersensitivity: Rare: angioedema

Infections: Infrequent: sepsis, herpes simplex, herpes zoster

Metabolic and Nutritional: Infrequent: hypophosphatemia, dehydration, gout, appetite disturbances, weight decreased

Rare: hyperkalemia, hyponatremia

Musculoskeletal: Less common: joint swelling

Infrequent: sciatica, joint and muscle stiffness 

Rare: avascular necrosis/hip osteonecrosis

Nervous System/Psychiatric: Less common: paresthesia

Infrequent: depression, anxiety, syncope, peripheral neuropathy, somnolence, migraine, memory impairment

Rare: increased intracranial pressure, cerebral edema (including fatalities), confusion, convulsions

Renal: Infrequent: renal failure, urinary frequency, hematuria

Reproductive: Infrequent: breast enlargement, menorrhagia, sexual dysfunction

Respiratory: Rare: interstitial pneumonitis, pulmonary fibrosis

Special Senses: Less common: conjunctivitis, vision blurred  

Infrequent: conjunctival hemorrhage, dry eye, vertigo, tinnitus 

Rare: macular edema, papilledema, retinal hemorrhage, glaucoma, vitreous hemorrhage

Vascular Disorders: Rare: thrombosis/embolism

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More resources:

Drugs.com Gleevec

MedFacts Gleevec

Micromedex Gleevec - Includes detailed dosage instructions.

FDA Gleevec

Facts & Comparisons Imatinib

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