Dasatinib - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS Myelosuppression and Bleeding Events : Severe thrombocytopenia, neutropenia, and anemia may occur.

Use caution if used concomitantly with medications that inhibit platelet function or anticoagulants.

Monitor complete blood counts regularly.

Transfuse and interrupt dasatinib when indicated. ( 2.5 , 5.1 , 5.2 ) Fluid Retention: Fluid retention, sometimes severe, including pleural effusions.

Manage with supportive care measures and/or dose modification. ( 2.5 , 5.3 ) Cardiovascular Toxicity: Monitor patients for signs or symptoms and treat appropriately.

Pulmonary Arterial Hypertension (PAH): Dasatinib may increase the risk of developing PAH which may be reversible on discontinuation.

Consider baseline risk and evaluate patients for signs and symptoms of PAH during treatment.

Stop dasatinib if PAH is confirmed.

QT Prolongation: Use dasatinib with caution in patients who have or may develop prolongation of the QT interval.

Severe Dermatologic Reactions : Individual cases of severe mucocutaneous dermatologic reactions have been reported.

Tumor Lysis Syndrome: Tumor lysis syndrome has been reported.

Maintain adequate hydration and correct uric acid levels prior to initiating therapy with dasatinib.

Embryo-Fetal Toxicity: Can cause fetal harm.

Advise patients of reproductive potential of potential risk to fetus and to use effective contraception. ( 5.9 , 8.1 , 8.3 ) Effects on Growth and Development in Pediatric Patients: epiphyses delayed fusion, osteopenia, growth retardation, and gynecomastia have been reported.

Monitor bone growth and development in pediatric patients.

Hepatotoxicity: 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.

5.1 Myelosuppression Treatment with dasatinib is associated with severe (NCI CTCAE Grade 3 or 4) thrombocytopenia, neutropenia, and anemia, which occur earlier and more frequently in patients with advanced phase CML or Ph+ ALL than in patients with chronic phase CML [see Adverse Reactions ].

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.

In pediatric patients with Ph+ ALL treated with dasatinib tablets in combination with chemotherapy, perform CBCs prior to the start of each block of chemotherapy and as clinically indicated.

During the consolidation blocks of chemotherapy, perform CBCs every 2 days until recovery.

Myelosuppression is generally reversible and usually managed by withholding dasatinib temporarily and/or dose reduction [see Dosage and Administration ] .

5.2 Bleeding-Related Events Dasatinib can cause serious and fatal bleeding.

In all CML or Ph+ ALL clinical studies, Grade ≥3 central nervous system (CNS) hemorrhages, including fatalities, occurred in <1% of patients receiving dasatinib.