Dasatinib interactions

Food & lifestyle

• grapefruit juice

  Major

  Metabolism

  Grapefruit and grapefruit juice may significantly increase the plasma concentrations of dasatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

  What to do: Patients treated with dasatinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Some authorities recommend close monitoring for toxicity (e.g., myelosuppression, bleeding complications, fluid retention, bradycardia or other conduction disturbances) and a reduction of dasatinib dosage to a range of 20 to 40 mg daily should be considered if there are no alternatives and concomitant use with a potent CYP450 3A4 inhibitor is necessary.

  3 sources

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. "Product Information. Sprycel (dasatinib)." Bristol-Myers Squibb (2006):
  3. Cerner Multum, Inc. "Australian Product Information." O 0

Conditions

Conditions in which Dasatinib needs care, as documented in this source.

• Bone Marrow Failure Disorders

  Moderate

  Thrombocytopenia, aplastic anemia, agranulocytosis and neutropenia occur with BCR-ABL tyrosine kinase inhibitors. Therapy with these drugs should be administered cautiously in patients with preexisting bone marrow suppression. A complete blood count should be performed every 1-2 weeks for the first month of therapy and then monthly thereafter, or as clinically indicated. To manage myelosuppression, withhold, reduce dose, or discontinue therapy as necessary.

  4 sources

  1. "Product Information. Gleevec (imatinib)." Novartis Pharmaceuticals (2022):
  2. "Product Information. Sprycel (dasatinib)." Bristol-Myers Squibb (2006):
  3. "Product Information. Tasigna (nilotinib)." Novartis Pharmaceuticals (2007):
  4. "Product Information. Bosulif (bosutinib)." Pfizer U.S. Pharmaceuticals Group (2012):

• Cardiovascular Diseases

  Moderate

  Cardiovascular events, including arterial vascular occlusive events, peripheral arterial occlusive events and ischemic cerebrovascular events have been reported in patients receiving tyrosine kinase inhibitors. If acute signs or symptoms of cardiovascular events occur, patients should seek immediate medical attention. The cardiovascular status and risk factors of patients should be evaluated prior to therapy and cardiovascular monitoring and management should take place during treatment.

  3 sources

  1. "Product Information. Gleevec (imatinib)." Novartis Pharmaceuticals (2022):
  2. "Product Information. Sprycel (dasatinib)." Bristol-Myers Squibb (2006):
  3. "Product Information. Tasigna (nilotinib)." Novartis Pharmaceuticals (2007):

• Hepatic Insufficiency

  Moderate

  Caution is advised when administering dasatinib to patients with hepatic impairment. Monitoring is recommended and dose adjustment might be necessary.

  1 source

  1. "Product Information. Sprycel (dasatinib)." Bristol-Myers Squibb (2006):

• Long QT Syndrome

  Moderate

  Dasatinib has shown to prolong QT interval in a concentration-dependent manner. Caution should be exercised specially in patients with congenital long QT syndrome, patients with hypokalemia, hypomagnesemia, or with history of arrhythmias and on antiarrhythmic medication. Hypokalemia or hypomagnesemia should be corrected before starting treatment. Patients at risk should be monitored with an EKG before treatment and periodically as clinically indicated. Dose adjustments might be needed.

  1 source

  1. "Product Information. Tasigna (nilotinib)." Novartis Pharmaceuticals (2007):

• Pulmonary Arterial Hypertension

  Moderate

  Dasatinib can increase the risk of developing pulmonary arterial hypertension (PAH) which may occur any time after treatment initiation, including after more than 1 year of treatment. Manifestations may include dyspnea, fatigue, hypoxia, and fluid retention. PAH may be reversible with treatment discontinuation. Caution should be exercised in patients with underlying cardiopulmonary disease. If PAH develops, treatment should be discontinued.

  1 source

  1. "Product Information. Sprycel (dasatinib)." Bristol-Myers Squibb (2006):

• Water-Electrolyte Imbalance

  Moderate

  Fluid retention occurs with BCR-ABL tyrosine kinase inhibitors therapy and may manifest as pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema. Caution should be taken when using these drugs in patients with preexisting fluid retention or congestive heart failure. Monitor and manage patients using standards of care. Interrupt, reduce dose or discontinue therapy as necessary.

  4 sources

  1. "Product Information. Gleevec (imatinib)." Novartis Pharmaceuticals (2022):
  2. "Product Information. Sprycel (dasatinib)." Bristol-Myers Squibb (2006):
  3. "Product Information. Tasigna (nilotinib)." Novartis Pharmaceuticals (2007):
  4. "Product Information. Bosulif (bosutinib)." Pfizer U.S. Pharmaceuticals Group (2012):