Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
WARNINGS AND PRECAUTIONS
- …In patients with chronic phase CML, perform complete blood counts (CBCs) every 2 weeks for 12 weeks, then every 3 months thereafter, or as clinically indicated. In patients with advanced phase CML or Ph+ ALL, perform CBCs weekly for the first 2 months and then monthly thereafter, or as clinically indicated
- SPRYCEL may cause fluid retention. After 5 years of follow-up in the randomized newly diagnosed chronic phase CML study (n=258), grade 3 or 4 fluid retention was reported in 5% of patients, including 3% of patients with grade 3 or 4 pleural effusion. In patients with newly diagnosed or imatinib resistant or intolerant chronic phase CML, grade 3 or 4 fluid retention occurred in 6% of patients treated with SPRYCEL at the recommended dose (n=548). In patients with advanced phase CML or Ph+ ALL treated with SPRYCEL at the recommended dose (n=304), grade 3 or 4 fluid retention was reported in 8% of patients, including grade 3 or 4 pleural effusion reported in 7% of patients. Evaluate patients who develop symptoms of pleural effusion or other fluid retention, such as new or worsened dyspnea on exertion or at rest, pleuritic chest pain, or dry cough promptly with a chest x-ray or additional diagnostic imaging as appropriate. Fluid retention events were typically managed by supportive care measures that may include diuretics or short courses of steroids. Severe pleural effusion may require thoracentesis and oxygen therapy. Consider dose reduction or treatment interruption
Severe Dermatologic Reactions
- Cases of severe mucocutaneous dermatologic reactions, including Stevens-Johnson syndrome and erythema multiforme, have been reported in patients treated with SPRYCEL. Discontinue permanently in patients who experience a severe mucocutaneous reaction during treatment if no other etiology can be identified.
- Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome
5 WARNINGS AND PRECAUTIONS
5.7 Embryofetal toxicity
- Advise females of reproductive potential to avoid pregnancy, which may include the use of contraception, during treatment with SPRYCEL, [see Use in Specific Populations (8.8)]
8 USE IN SPECIFIC POPULATIONS
8.8 Females of Reproductive Potential
- SPRYCEL can cause fetal harm when ....
17 PATIENT COUNSELING INFORMATION
17.4 Embryo-Fetal Toxicity
- Patients should be informed that SPRYCEL can cause fetal harm when administered to a pregnant woman. Women should be advised of the potential hazard to the fetus and to avoid becoming pregnant. If SPRYCEL is used during pregnancy, or if the patient becomes pregnant while taking SPRYCEL, the patient should be apprised of the potential hazard to the fetus [see Warnings and Precautions (5.7) and Use in Specific Populations (8.1, 8.8).]
- In the newly diagnosed chronic phase CML trial with a minimum of 36 months follow up and median duration of therapy of 37 months, the median average daily dose was 99 mg.
- In the imatinib resistant or intolerant CML or Ph+ ALL clinical trials, 1520 patients had a minimum of 2 years follow up and 662 patients with chronic phase CML had a minimum of 60 months follow up (starting dosage 100 mg once daily, 140 mg once daily, 50 mg twice daily, or 70 mg twice daily). Among patients with chronic phase CML and resistance or intolerance to prior imatinib therapy, the median duration of treatment with Sprycel 100 mg once daily was 37 months (range 1–65 months). The median duration of treatment with...
- pulmonary arterial hypertension
WARNINGS and PRECAUTIONS
Congestive Heart Failure, Left Ventricular Dysfunction, and Myocardial Infarction
- Cardiac adverse reactions were reported in 5.8% of 258 patients taking Sprycel, including 1.6% of patients with cardiomyopathy, heart failure congestive, diastolic dysfunction, fatal myocardial infarction, and left ventricular dysfunction. Monitor patients for signs or symptoms consistent with cardiac dysfunction and treat appropriately.
Dose Adjustment for Adverse Reactions
- In clinical studies, myelosuppression was managed by dose interruption, dose reduction, or discontinuation of study therapy. Hematopoietic growth factor has been used in patients with resistant myelosuppression. Guidelines for dose modifications are summarized in Table 1.
(revision of the Adverse Reactions section of the package insert to include discontinuation rate due to myelosuppression to 5%)