Skip to Content

Dasatinib

Class: Antineoplastic Agents
- Kinase Inhibitors
- Receptor Tyrosine Kinase Inhibitors
- Tyrosine Kinase Inhibitors
VA Class: AN900
Chemical Name: N-(2-Chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide, monohydrate
Molecular Formula: C22H26C1N7O2S • H2O
CAS Number: 863127-77-9
Brands: Sprycel

Medically reviewed by Drugs.com on Aug 3, 2020. Written by ASHP.

Introduction

Antineoplastic agent; a kinase inhibitor.

Uses for Dasatinib

Chronic Myelogenous Leukemia (CML)

Treatment of newly diagnosed Philadelphia chromosome-positive (Ph+) CML in adults who are in the chronic phase of the disease.

Treatment of Ph+ CML in adults who are in myeloid or lymphoid blast crisis, in the accelerated phase, or in the chronic phase of the disease, after failure (secondary to resistance or intolerance) of prior therapy including imatinib.

Designated an orphan drug by FDA for use in the treatment of CML.

Acute Lymphocytic (Lymphoblastic) Leukemia (ALL)

Treatment of Philadelphia chromosome-positive (Ph+) ALL in adults following failure (secondary to resistance or intolerance) of prior therapy (designated an orphan drug by FDA for this use).

Dasatinib Dosage and Administration

General

  • Use under supervision of a qualified clinician.

  • Optimal duration of therapy has not been clearly established. Effect of discontinuance of treatment after achievement of a complete cytogenetic response has not been established.

Administration

Oral Administration

Administer orally once daily (morning or evening) without regard to meals.

Administer at the same time each day.

Swallow tablets whole; do not cut, chew, or crush.

Dosage

Adjustments may be necessary when used in conjunction with CYP3A4 inhibitors or inducers. (See Drugs Affecting Hepatic Microsomal Enzymes under Interactions.)

Adults

CML
Chronic Phase
Oral

100 mg once daily. If hematologic or cytogenetic response is not achieved, increase dosage to 140 mg once daily.

Continue treatment until evidence of disease progression or until no longer tolerated by the patient.

Accelerated Phase or Blast Crisis
Oral

140 mg once daily. If hematologic or cytogenetic response is not achieved, increase dosage to 180 mg once daily.

Continue treatment until evidence of disease progression or until no longer tolerated by the patient.

ALL
Oral

140 mg once daily. If hematologic or cytogenetic response is not achieved, increase dosage to 180 mg once daily.

Continue treatment until evidence of disease progression or until no longer tolerated by the patient.

Dosage Modification for Toxicity
Nonhematologic Adverse Effects

If a severe nonhematologic adverse reaction occurs, withhold dasatinib until the event has resolved or improved. Thereafter, resume therapy, as appropriate, at a reduced dosage depending on the initial severity of the event.

Adverse Hematologic Effects

Temporary interruption, dosage reduction, or discontinuance is indicated in patients experiencing severe neutropenia and/or thrombocytopenia. Hematopoietic growth factor has been used in patients with resistant myelosuppression.

Dosage Adjustments for Neutropenia and Thrombocytopenia: Chronic Phase CML

Initial Dosage

Episode of Neutropenia or Thrombocytopenia (Hematologic Measurements)

Dosage Adjustment

100 mg once daily

First episode (ANC <500/mm3 or platelets <50,000/mm3)

Withhold dasatinib; may resume at original dosage (100 mg once daily) if ANC reaches ≥1000/mm3 and platelets reach ≥50,000/mm3 within 7 days

Second episode (ANC <500/mm3 lasting >7 days or platelets <25,000/mm3)

Withhold dasatinib; may resume at reduced dosage of 80 mg once daily when ANC reaches ≥1000/mm3 and platelets reach ≥50,000/mm3

Third episode (ANC <500/mm3 lasting >7 days or platelets <25,000/mm3)

Patients receiving dasatinib for newly diagnosed disease: Withhold dasatinib; may resume at reduced dosage of 50 mg once daily when ANC reaches ≥1000/mm3 and platelets reach ≥50,000/mm3

Patients receiving dasatinib following failure of prior therapy: Discontinue drug

Dosage Adjustments for Neutropenia and Thrombocytopenia: Accelerated Phase or Blast Phase CML and Ph+ ALL

Initial Dosage

Hematologic Measurements

Dosage Adjustment

140 mg once daily

ANC <500/mm3 or platelets <10,000/mm3

1. If cytopenia is unrelated to leukemia (as determined by marrow aspirate or biopsy), discontinue dasatinib until ANC ≥1000/mm3 and platelets ≥20,000/mm3

2. Resume treatment at original dosage (140 mg once daily)

3. If recurrence of ANC <500/mm3 or platelets <10,000/mm3 occurs, repeat step 1 and resume therapy at a reduced dosage of 100 mg once daily (following a second episode) or 80 mg once daily (following a third episode)

4. If cytopenia is related to leukemia (as determined by marrow aspirate or biopsy), consider increasing dosage to 180 mg once daily

Special Populations

Hepatic Impairment

Dosage adjustment not necessary. (See Hepatic Impairment under Cautions.)

Renal Impairment

No special dosage recommendations at this time. (See Renal Impairment under Cautions.)

Geriatric Patients

No special dosage recommendations at this time. (See Geriatric Use under Cautions.)

Cautions for Dasatinib

Contraindications

  • No known contraindications.

Warnings/Precautions

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity and embryolethality demonstrated in animals. Avoid pregnancy during therapy. If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.

Use adequate forms of contraception during therapy.

Women who are pregnant should not handle crushed or broken dasatinib tablets.

Hematologic Effects

Myelosuppression (principally severe neutropenia, anemia, and thrombocytopenia) occurs commonly and is usually reversible; more frequent in patients in the accelerated or blast phase of CML and in those with Ph+ ALL than in patients in the chronic phase of CML.

Temporary suspension of therapy or dosage reduction may be required if hematologic toxicity occurs. (See Dosage Modification for Toxicity under Dosage and Administration.)

Perform CBCs weekly during the first 2 months of therapy and monthly (or as clinically indicated) thereafter.

Hemorrhage

Risk of severe hemorrhage, including potentially fatal CNS or GI hemorrhage; usually associated with severe thrombocytopenia.

Severe GI hemorrhage may require treatment interruption and transfusions.

Use with caution in patients receiving anticoagulants or drugs that inhibit platelet function. (See Specific Drugs under Interactions.)

Fluid Retention

Risk of potentially severe fluid retention (i.e., pleural effusion, pericardial effusion, pulmonary edema, ascites, generalized edema).

Fluid retention generally managed with supportive care (e.g., diuretics, short course of corticosteroids).

Evaluate symptoms suggestive of pleural effusion (e.g., dyspnea, dry cough) by chest radiograph. Severe pleural effusion may require thoracentesis and oxygen therapy.

Hepatic Effects

Grade 3 or 4 elevations of serum bilirubin, AST, and/or ALT reported; more frequent in patients in myeloid or lymphoid blast phase of CML and in those with Ph+ ALL.

Electrolyte Disturbances

Grade 3 or 4 hypophosphatemia and hypocalcemia reported; more frequent in patients in myeloid or lymphoid blast phase of CML and in those with Ph+ ALL.

Hypocalcemia generally managed with oral calcium supplementation.

Prolongation of QT Interval

May cause prolongation of the QT interval. Use with caution in patients who have or may develop prolongation of the QT interval (e.g., hypokalemia, hypomagnesemia, congenital long QT syndrome, use of drugs known to prolong QT interval, cumulative high-dose anthracycline therapy).

Correct hypokalemia or hypomagnesemia prior to administration of dasatinib.

Left Ventricular Dysfunction, CHF, and MI

Cardiomyopathy, CHF, diastolic dysfunction, fatal MI, and left ventricular dysfunction reported; monitor patient for manifestations of cardiac dysfunction and provide appropriate treatment if they occur.

Pulmonary Arterial Hypertension (PAH)

May increase risk for development of PAH. May occur at any time after initiation of therapy (e.g., 8–60 months); reported most often in patients with comorbidities or receiving other drugs concomitantly. May be reversible upon discontinuance of dasatinib.

Evaluate patient for manifestations of cardiopulmonary disease before and during dasatinib therapy. Consider PAH in any patient with dyspnea, fatigue, hypoxia, and fluid retention; however, exclude other etiologies of dyspnea prior to initiating invasive diagnostic procedures for PAH.

Interruption of therapy accompanied by monitoring for improvement may be considered if PAH is suspected. If PAH is confirmed (e.g., by cardiac catheterization), permanently discontinue the drug.

Lactose-intolerant Patients

140-mg daily dosage contains 189 mg of lactose monohydrate; 100-mg daily dosage contains 135 mg of lactose monohydrate.

Specific Populations

Pregnancy

Category D. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether dasatinib is distributed into milk. Discontinue nursing because of potential risk to nursing infants.

Pediatric Use

Safety and efficacy not established in patients <18 years of age.

Geriatric Use

No substantial difference in efficacy relative to younger adults, but patients ≥65 years of age are more likely to experience toxicity.

Hepatic Impairment

Not studied in patients with hepatic impairment (ALT and/or AST >2.5 times ULN and/or total bilirubin >2 times ULN); however the drug is metabolized extensively in the liver. Use with caution.

Renal Impairment

Not studied in patients with renal impairment (Scr >1.5 times ULN); however, renal impairment not expected to decrease dasatinib clearance. (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

Patients receiving dasatinib as first-line therapy: Neutropenia, thrombocytopenia, anemia, fluid retention (e.g., pleural effusion or superficial localized edema), diarrhea, headache, musculoskeletal pain, rash.

Patients receiving dasatinib following failure of prior therapy: Fluid retention (e.g., superficial and/or localized edema, generalized edema, pleural effusion, pericardial effusion, CHF or cardiac dysfunction, pulmonary edema), neutropenia, thrombocytopenia, anemia, hemorrhage (e.g., GI or CNS hemorrhage), diarrhea, vomiting, abdominal pain, nausea, headache, fatigue, pyrexia, musculoskeletal pain, myalgia, arthralgia, rash, dyspnea, hypophosphatemia, hypokalemia, hypocalcemia, febrile neutropenia, infection (e.g., bacterial, viral, fungal).

Interactions for Dasatinib

Metabolized principally by CYP3A4; weak inhibitor of CYP3A4.

Does not inhibit CYP isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, or 2E1; does not induce human CYP isoenzymes.

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: Potential pharmacokinetic interaction (increased plasma dasatinib concentrations). Consider alternative drugs with no or less enzyme inhibition potential. If concomitant use with a potent CYP3A4 inhibitor cannot be avoided, consider reducing dasatinib dosage to 20 mg daily (if current dosage is 100 mg daily) or to 40 mg daily (if current dosage is 140 mg daily) based on pharmacokinetic considerations (no clinical data with these dosage adjustments available). If dasatinib is not tolerated following dosage reduction, discontinue the CYP3A4 inhibitor or interrupt dasatinib therapy until treatment with the CYP3A4 inhibitor is completed. Upon discontinuance of a potent CYP3A4 inhibitor, allow approximately 1 week to elapse before increasing dasatinib dosage.

Inducers of CYP3A4: Potential pharmacokinetic interaction (decreased plasma dasatinib concentrations). Avoid concomitant use of potent CYP3A4 inducers; consider alternative drugs with no or less enzyme induction potential. If concomitant therapy cannot be avoided, consider increase in dasatinib dosage and closely monitor patient for toxicity.

Drugs Affecting Coagulation

Potential for bleeding; use anticoagulants and drugs that inhibit platelet function concomitantly with caution. Initial clinical trials of dasatinib excluded patients receiving such drugs; subsequent trials permitted use of anticoagulants, aspirin, and NSAIAs if patient's platelet count exceeded 50,000–75,000/mm3.

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP3A4: Potential pharmacokinetic interaction (increased plasma substrate concentrations).

Specific Drugs and Foods

Drug or Food

Interaction

Comments

Alfentanil

Possible increased plasma concentrations and AUC of alfentanil

Use concomitantly with caution

Antacids (e.g., calcium carbonate, aluminum and magnesium hydroxides)

Possible decreased plasma dasatinib concentrations, secondary to apparent pH-dependence of dasatinib solubility Dasatinib AUC unchanged when administered 2 hours after antacid (aluminum and magnesium hydroxides) but decreased 55% when administered concomitantly with antacid

Administer antacids ≥2 hours before or ≥2 hours after a dose of dasatinib

Anticoagulants (e.g., warfarin)

Possible increased risk of hemorrhage

Use concomitantly with caution

Anticonvulsants (carbamazepine, phenobarbital, phenytoin)

Possible decreased plasma dasatinib concentrations

Avoid concomitant use if possible; if concomitant therapy necessary, consider increasing dasatinib dosage and closely monitor for toxicity

Antifungals, azoles (i.e., itraconazole, ketoconazole, voriconazole)

Possible increased plasma dasatinib concentrations and increased exposure to dasatinib Ketoconazole: Increased dasatinib AUC by fivefold and peak concentration by fourfold

Avoid concomitant use if possible; if concomitant therapy necessary, closely monitor for toxicity and consider reducing dasatinib dosage to 20 mg daily (if current dosage is 100 mg daily) or 40 mg daily (if current dosage is 140 mg daily) (see Drugs Affecting Hepatic Microsomal Enzymes under Interactions)

Antihistamines (terfenadine and astemizole [no longer commercially available])

Possible increased plasma concentrations of terfenadine and astemizole

Cisapride

Possible increased plasma concentrations of cisapride

Use concomitantly with caution

Dexamethasone

Possible decreased plasma dasatinib concentrations

Avoid concomitant use if possible; if concomitant therapy necessary, consider increasing dasatinib dosage and closely monitor for toxicity

Ergot alkaloids (dihydroergotamine, ergotamine)

Possible increased plasma concentrations of ergot alkaloids

Use concomitantly with caution

Fentanyl

Possible increased plasma concentrations of fentanyl

Use concomitantly with caution

Grapefruit juice

Possible increased plasma dasatinib concentrations

Avoid concomitant use

Histamine H2-receptor antagonists (e.g., cimetidine, famotidine, ranitidine)

Possible decreased plasma dasatinib concentrations, secondary to apparent pH-dependence of dasatinib solubility Famotidine: Decreased dasatinib AUC and peak concentration by 61–63% when given 10 hours before dasatinib

Concomitant use not recommended

HIV protease inhibitors (e.g., atazanavir, indinavir, nelfinavir, ritonavir, saquinavir)

Possible increased plasma dasatinib concentrations and increased exposure to dasatinib

Avoid concomitant use if possible; if concomitant therapy necessary, closely monitor for toxicity and consider reducing dasatinib dosage to 20 mg daily (if current dosage is 100 mg daily) or 40 mg daily (if current dosage is 140 mg daily) (see Drugs Affecting Hepatic Microsomal Enzymes under Interactions)

Immunosuppressive agents (cyclosporine, sirolimus, tacrolimus)

Possible increased plasma concentrations of immunosuppressive agents

Use concomitantly with caution

Macrolide antibiotics (i.e., clarithromycin, erythromycin, telithromycin)

Possible increased plasma dasatinib concentrations and increased exposure to dasatinib

Avoid concomitant use if possible; if concomitant therapy necessary, closely monitor for toxicity and consider reducing dasatinib dosage to 20 mg daily (if current dosage is 100 mg daily) or 40 mg daily (if current dosage is 140 mg daily) (see Drugs Affecting Hepatic Microsomal Enzymes under Interactions)

Nefazodone

Possible increased plasma dasatinib concentrations and increased exposure to dasatinib

Avoid concomitant use if possible; if concomitant therapy necessary, closely monitor for toxicity and consider reducing dasatinib dosage to 20 mg daily (if current dosage is 100 mg daily) or 40 mg daily (if current dosage is 140 mg daily) (see Drugs Affecting Hepatic Microsomal Enzymes under Interactions)

NSAIAs (e.g., aspirin)

Possible increased risk of hemorrhage

Use concomitantly with caution

Pimozide

Possible increased plasma concentrations of pimozide

Use concomitantly with caution

Proton-pump inhibitors (e.g., esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole)

Possible decreased plasma dasatinib concentrations, secondary to apparent pH-dependence of dasatinib solubility Omeprazole: Decreased dasatinib AUC and peak concentration by 42–43% when given 22 hours before dasatinib

Concomitant use not recommended

Quinidine

Possible increased plasma concentrations of quinidine

Use concomitantly with caution

Rifamycins (rifabutin, rifampin)

Possible decreased plasma dasatinib concentrations and AUC of dasatinib Rifampin: Decreased dasatinib AUC and peak concentration by 81–82%

Avoid concomitant use if possible; if concomitant therapy necessary, consider increasing dasatinib dosage and closely monitor for toxicity

St. John’s wort (Hypericum perforatum)

Potential for unpredictable decreases in plasma dasatinib concentrations

Concomitant use not recommended

Simvastatin

Possible increased plasma concentrations and AUC of simvastatin

Use concomitantly with caution

Dasatinib Pharmacokinetics

Absorption

Onset

Following oral administration, peak plasma concentrations are attained within 0.5–6 hours.

Special Populations

In patients with moderate or severe hepatic impairment (Child-Pugh class B or C), peak plasma concentrations and AUC (normalized for differences in administered doses) are lower than in healthy individuals; differences not considered clinically important.

Distribution

Extent

Extensively distributed into the extravascular space.

Plasma Protein Binding

Approximately 96 and 93% for dasatinib and active metabolite, respectively.

Elimination

Metabolism

Metabolized in the liver, principally by CYP3A4, to an active metabolite and several inactive metabolites.

Elimination Route

Eliminated principally in feces (85%) mainly as metabolites and to a lesser extent in urine (4%).

Half-life

3–5 hours.

Special Populations

No clinically relevant effects of age and gender on pharmacokinetics.

Stability

Storage

Oral

Tablets

20–25°C (may be exposed to 15–30°C).

Actions

  • Inhibits multiple tyrosine kinases including Bcr-Abl, the Src family (Src, Lck, Yes, Fyn), c-Kit, EphA-2, and platelet-derived growth factor (PDGFR)-β; predicted to bind to multiple conformations of the Abl kinase.

  • Inhibits Bcr-Abl tyrosine kinase, an abnormal protein created by the Philadelphia chromosome abnormality in CML and Ph+ ALL that exhibits enhanced tyrosine kinase activity (i.e., increased phosphorylation of tyrosine residues).

  • Overcomes imatinib resistance resulting from Bcr-Abl kinase domain mutations, activation of alternate signaling pathways involving the Src family kinases (Lyn, Hck), and multidrug-resistance gene overexpression.

Advice to Patients

  • Importance of taking only as prescribed. Take at about the same time each day; do not discontinue therapy without first consulting clinician.

  • Importance of advising patients to swallow dasatinib tablets whole with water and not to break, chew, cut, or crush the tablets. Importance of not drinking grapefruit juice while taking the drug.

  • Risk of severe fluid retention, bleeding, and cytopenia. Importance of immediately informing clinician if fever, any bleeding or bruising, swelling, weight gain, or increasing shortness of breath occurs.

  • Importance of close medical supervision in patients receiving dasatinib.

  • Importance of informing clinicians if patient is lactose intolerant.

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid pregnancy during therapy, advise pregnant women of risk to the fetus, and advise women to utilize effective contraception during therapy. Importance of advising patients that pregnant women should not handle crushed or broken dasatinib tablets.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Dasatinib

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

20 mg

Sprycel

Bristol Myers-Squibb

50 mg

Sprycel

Bristol Myers-Squibb

70 mg

Sprycel

Bristol Myers-Squibb

80 mg

Sprycel

Bristol Myers-Squibb

100 mg

Sprycel

Bristol Myers-Squibb

140 mg

Sprycel

Bristol Myers Squibb

AHFS DI Essentials™. © Copyright 2021, Selected Revisions August 13, 2014. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

Show article references

Frequently asked questions