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).

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.

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.

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.

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

(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.

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

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.

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

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

More resources:

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