Imatinib - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS • Edema and severe fluid retention have occurred.

Weigh patients regularly and manage unexpected rapid weight gain by drug interruption and diuretics. ( 5.1 , 6.1 ) • Cytopenias, particularly anemia, neutropenia, and thrombocytopenia, have occurred.

Manage with dose reduction, dose interruption, or discontinuation of treatment.

Perform complete blood counts weekly for the first month, biweekly for the second month, and periodically thereafter. • Severe congestive heart failure and left ventricular dysfunction have been reported, particularly in patients with comorbidities and risk factors.

Monitor and treat patients with cardiac disease or risk factors for cardiac failure. • Severe hepatotoxicity, including fatalities may occur.

Assess liver function before initiation of treatment and monthly thereafter or as clinically indicated.

Monitor liver function when combined with chemotherapy known to be associated with liver dysfunction. • Grade 3/4 hemorrhage has been reported in clinical studies in patients with newly diagnosed CML and with GIST.

GI tumor sites may be the source of GI bleeds in GIST. • Gastrointestinal (GI) perforations, some fatal, have been reported. • Cardiogenic shock/left ventricular dysfunction has been associated with the initiation of imatinib mesylate in patients with conditions associated with high eosinophil levels (e.g., HES, MDS/MPD, and ASM). • Bullous dermatologic reactions (e.g., erythema multiforme and Stevens-Johnson syndrome) have been reported with the use of imatinib mesylate. • Hypothyroidism has been reported in thyroidectomy patients undergoing levothyroxine replacement.

Closely monitor TSH levels in such patients. • Fetal harm can occur when administered to a pregnant woman.

Apprise women of the potential harm to the fetus, and to use effective contraception. ( 5.10 , 8.1 ) • Growth retardation occurring in children and pre-adolescents receiving imatinib mesylate has been reported.

Close monitoring of growth in children under imatinib mesylate treatment is recommended. ( 5.11 , 6.2 ) • Tumor Lysis Syndrome.

Close monitoring is recommended. • Reports of motor vehicle accidents have been received in patients receiving imatinib mesylate.

Caution patients about driving a car or operating machinery. • Renal Toxicity.

A decline in renal function may occur in patients receiving imatinib mesylate tablets.

Evaluate renal function at baseline and during therapy, with attention to risk factors for renal dysfunction.

5.1 Fluid Retention and Edema Imatinib mesylate is often associated with edema and occasionally serious fluid retention [ see Adverse Reactions ].

Weigh and monitor patients regularly for signs and symptoms of fluid retention.

Investigate unexpected rapid weight gain carefully and provide appropriate treatment.

The probability of edema was increased with higher imatinib mesylate dose and age greater than 65 years in the CML studies.

Severe superficial edema was reported in 1.5% of newly diagnosed CML patients taking imatinib mesylate, and in 2% to 6% of other adult CML patients taking imatinib mesylate.

In addition, other severe fluid retention (e.g., pleural effusion, pericardial effusion, pulmonary edema, and ascites) reactions were reported in 1.3% of newly diagnosed CML patients taking imatinib mesylate, and in 2% to 6% of other adult CML patients taking imatinib mesylate.

Severe fluid retention was reported in 9% to 13.1% of patients taking imatinib mesylate for GIST [see Adverse Reactions ].

In a randomized trial in patients with newly diagnosed Ph+CML in chronic phase comparing imatinib mesylate and nilotinib, severe (Grade 3 or 4) fluid retention occurred in 2.5% of patients receiving imatinib mesylate and in 3.9% of patients receiving nilotinib 300 mg twice daily.

Effusions (including pleural effusion, pericardial effusion, ascites) or pulmonary edema were observed in 2.1% (none were Grade 3 or 4) of patients in the imatinib mesylate arm and 2.2% (0.7% Grade 3 or 4) of patients in the nilotinib 300 mg twice daily arm.

5.2 Hematologic Toxicity Treatment with imatinib mesylate tablets is associated with anemia, neutropenia, and thrombocytopenia.