Dasatinib

Dasatinib is a Prescription medicine used to treat the symptoms of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). 

• Dasatinib is available under the following different brand names: Sprycel

Adult and pediatric dosage

Tablet

• 20mg
• 50mg
• 70mg
• 80mg
• 100mg
• 140mg

Chronic Myeloid Leukemia

Adult dosage

• Newly diagnosed
  • Start 100 mg orally once daily (morning or evening)
  • May increase to 140 mg once daily if inadequate response
• Advanced CML
  • Start 140 mg orally once daily
  • May increase to 180 mg once daily if inadequate response

Pediatric dosage

• Indicated for children above 1 year
• Recommended initial dosage based on body weight
• Children less than 10 kg: Not recommended
• Children between 10 to less than 20 kg: 40 mg orally once daily
• Children between 20 to less than 30 kg: 60 mg orally once daily
• Children between 30 to less than 45 kg: 70 mg orally once daily
• Children more than or equal to 45 kg: 100 mg orally once daily
• Recommended dose escalation if a hematological or cytogenetic response is not achieved
• Starting dose 40 mg orally once daily: May increase 50 mg orally once daily
• Starting dose 60 mg orally once daily: May increase 70 mg orally once daily
• Starting dose 70 mg orally once daily: May increase 90 mg orally once daily
• Starting dose 100 mg orally once daily: May increase 120 mg orally once daily

Acute Lymphoblastic Leukemia

Adult dosage

• Start 140 mg orally once daily
• May increase to 180 mg orally once daily if inadequate response

Pediatric dosage

• Indicated for children above 1 year
• Begin therapy on or before day 15 of induction chemotherapy, when the diagnosis is confirmed, and continue for 2 years
• Recommended initial dosage based on body weight
• Children less than 10 kg: Not recommended
• Children between 10 to less than 20 kg: 40 mg orally once daily
• Children between 20 to less than 30 kg: 60 mg orally once daily
• Children between 30 to less than 45 kg: 70 mg orally once daily
• Children more than or equal to 45 kg: 100 mg orally once daily

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Dasatinib include:

• nausea,
• diarrhea,
• stomach pain,
• headache,
• muscle pain,
• pain in hands or feet,
• breathing problems,
• skin rash, and
• tiredness.

Serious side effects of Dasatinib include:

• chest pain,
• tiredness,
• swelling in the feet, lower legs, or midsection,
• blue-colored lips and skin,
• severe ongoing nausea,
• diarrhea,
• severe headaches,
• extreme tiredness,
• muscle or joint pain,
• pain when breathing,
• swelling,
• rapid weight gain,
• pounding heartbeats,
• fluttering in the chest,
• easy bruising,
• unusual bleeding (nose, mouth, vagina, or rectum),
• purple or red pinpoint spots under the skin,
• signs of an allergic reaction: hives, difficult breathing, swelling in the face or throat,
• severe skin reaction: fever, sore throat, burning in the eyes, skin pain, red or purple skin rash that spreads and causes blistering and peeling,
• signs of bleeding: blood in urine, bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds, confusion, headache, problems with speech,
• low blood cell counts fever, chills, tiredness, flu-like symptoms, mouth sores, skin sores, pale skin, cold hands, and feet, feeling light-headed, and
• signs of tumor cell breakdown--muscle cramps, nausea, vomiting, weakness, swelling, feeling short of breath, or seizure.

Rare side effects of Dasatinib include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Dasatinib has severe interactions with the following drugs:
  • lefamulin
  • pimozide
  • saquinavir
• Dasatinib has serious interactions with at least 109 other drugs.
• Dasatinib has moderate interactions with at least 256 other drugs.
• Dasatinib has minor interactions with at least 52 other drugs. 

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Dasatinib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Dasatinib?”

Cautions

• Use caution in hepatic impairment
• Use with caution in patients who have or may develop prolongation of QT interval; may increase risk of prolongation of QTc in patients including those with hypokalemia or hypomagnesemia, patients with congenital long QT syndrome, patients taking antiarrhythmic medicines or other medicinal products that lead to QT prolongation, and cumulative high-dose anthracycline therapy; correct hypokalemia or hypomagnesemia before and during therapy
• Cardiac adverse reactions were reported in 5.8% of 258 patients including cardiomyopathy (1.6%), congestive heart failure, diastolic dysfunction, fatal myocardial infarction, and left ventricular dysfunction; monitor patients for signs or symptoms and treat appropriately
• Tumor lysis syndrome reported; maintain adequate hydration and correct uric acid levels before initiating therapy; monitor electrolyte levels; patients with advanced-stage disease and/or high tumor burden may be at increased risk and should be monitored more frequently
• Risk of fluid retention and pleural/pericardial effusion; manage with supportive care measures and/or dose modification; 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
• Embryofetal toxicity was reported (see Pregnancy)
• In pediatric trials of dasatinib in chronic phase CML after at least 2 years of treatment, adverse reactions associated with bone growth and development were reported, including epiphyses delayed fusion, osteopenia, growth retardation, and gynecomastia; monitor bone growth and development in pediatric patients
• Myelosuppression includes severe thrombocytopenia, neutropenia, and anemia
  • May managed by dose interruption, dose reduction, or discontinuation of therapy
  • Hematopoietic growth factor has been used with resistant myelosuppression
• Patients with chronic phase CML and pediatric Ph+ ALL
  • Perform complete blood cell counts (CBCs) every 2 weeks for 12 weeks, then every 3Months thereafter, or as clinically indicated
  • Perform CBCs weekly for the first 2 months and then monthly thereafter, or as clinically indicated in patients with advanced phase CML or Ph+ ALL
• Pediatric patients with Ph+ ALL treated in combination with chemotherapy
  • Perform CBCs before the start of each block of chemotherapy and as clinically indicated
  • During consolidation blocks of chemotherapy, perform CBCs every 2 days until recovery
• Bleeding
  • Can cause serious and fatal bleeding; incidence of Grade 3/4 hemorrhage, most commonly gastrointestinal, reported, requiring treatment interruptions and transfusions
  • Most bleeding events associated with severe thrombocytopenia; also shown to cause platelet dysfunction in vitro
  • Concomitant medications that inhibit platelet function or anticoagulants may increase the risk of hemorrhage
  • Severe hemorrhage may require treatment interruption and transfusion
• Pulmonary arterial hypertension
  • Increased risk of developing pulmonary arterial hypertension (PAH)
  • It may be reversible upon discontinuation of therapy
  • Evaluate patients for signs and symptoms of underlying cardiopulmonary disease before initiation and during treatment
  • If PAH confirmed permanently discontinue therapy
• Severe mucocutaneous dermatologic reactions
  • Cases of severe mucocutaneous dermatologic reactions, including Stevens-Johnson syndrome and erythema multiforme, reported
  • Discontinue permanently in patients who experience a severe mucocutaneous reaction during treatment if no other etiology can be identified
• Drug interactions overview
  • Avoid concomitant CYP3A4 inducers/inhibitors
  • If unavoidable, consider dose modification as appropriate (see Dosage Modifications)
  • Coadministration of dasatinib with a gastric acid reducing agent may decrease the concentrations of dasatinib and reduce efficacy (see Dosage Modifications)

Pregnancy and Lactation

• Based on limited human data, dasatinib can cause fetal harm when administered to a pregnant woman; adverse pharmacologic effects (e.g., hydrops fetalis, fetal leukopenia, and fetal thrombocytopenia) have been reported with maternal exposure to Dasatinib
• Advise a pregnant woman of the potential risk to a fetus
• Transplacental transfer of dasatinib has been reported
• Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for 30 days after the last dose
• Based on animal data, dasatinib may result in damage to female and male reproductive tissues
• Lactation
  • No data are available regarding the presence of dasatinib in human milk, the effects of the drug on the breastfed child, or the effects of the drug on milk production
  • However, dasatinib is present in the milk of lactating rats