SPRYCEL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SPRYCEL (SPRYCEL).
Dasatinib is a dual tyrosine kinase inhibitor targeting BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ. It binds to the ATP-binding site of BCR-ABL and inhibits proliferation and induces apoptosis in Philadelphia chromosome-positive (Ph+) leukemic cells.
| Metabolism | Dasatinib is extensively metabolized in the liver, primarily by CYP3A4, with minor contributions from flavin-containing monooxygenase 3 (FMO3) and UGT1A9. The major active metabolite is equipotent to the parent drug but constitutes approximately 5% of the circulating dose. |
| Excretion | Primarily fecal (85%) as unchanged drug and metabolites; renal excretion accounts for <10% of the dose. |
| Half-life | Terminal elimination half-life is approximately 3–4 hours for dasatinib, with a longer half-life of 8–10 hours for its active metabolite; clinical context: supports twice-daily dosing. |
| Protein binding | Approximately 96% bound to plasma proteins, predominantly albumin and alpha-1 acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 2600 L (about 37 L/kg for a 70 kg individual), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 14–34% due to extensive first-pass metabolism; increases 2-fold with a high-fat meal, so take on an empty stomach. |
| Onset of Action | Oral: peak plasma concentrations occur within 0.5–6 hours; pharmacodynamic effects (e.g., BCR-ABL inhibition) are observed within 24 hours of first dose. |
| Duration of Action | Duration of BCR-ABL inhibition persists for at least 24 hours after a single dose; clinical response requires continuous daily dosing. |
| Action Class | Tyrosine kinase inhibitors |
| Brand Substitutes | Dasamyl 50mg Tablet, Nextki 50mg Tablet, Daslemia 50mg Tablet, Dasatrue 50mg Tablet, Dasamed 50mg Tablet, Dasamyl 70mg Tablet, Daslemia 70 Tablet, Nextki 70mg Tablet, Dasamed 70mg Tablet, Dasatrue 70mg Tablet, Spnib 20mg Tablet, Dasamed 20mg Tablet, Dasafav 20 Tablet, Dasashil 20mg Tablet, Alsatinib 20mg Tablet |
100 mg orally once daily, with or without food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment recommended for mild to moderate renal impairment. For severe renal impairment (CrCl <30 mL/min), use with caution and monitor closely due to limited data; no specific dose adjustment established. |
| Liver impairment | Child-Pugh A: 100 mg once daily. Child-Pugh B: reduce starting dose to 70 mg once daily. Child-Pugh C: reduce starting dose to 50 mg once daily. |
| Pediatric use | For Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: weight-based dosing: <20 kg: 50 mg once daily; 20 to <45 kg: 70 mg once daily; ≥45 kg: 100 mg once daily. For Philadelphia chromosome-positive acute lymphoblastic leukemia: dosing as per CML chronic phase. |
| Geriatric use | No specific dose adjustment is required for elderly patients. Clinical trials included patients 65 years and older, and no dose adjustments were recommended. Monitor renal function and concomitant medications due to potential for increased toxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SPRYCEL (SPRYCEL).
| Breastfeeding | It is not known whether dasatinib is excreted in human milk. However, dasatinib is excreted in the milk of lactating rats at concentrations approximately 3- to 5-fold higher than those in maternal plasma. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from dasatinib, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. No M/P ratio is available in humans. |
| Teratogenic Risk | Pregnancy Category D. Based on its mechanism of action (BCR-ABL tyrosine kinase inhibitor) and animal studies, SPRYCEL (dasatinib) is expected to cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies in pregnant women. Dasatinib was embryotoxic and fetotoxic in rats and rabbits at doses below the human therapeutic dose. Use in pregnancy should be avoided unless the potential benefit justifies the potential risk to the fetus. If the patient becomes pregnant while taking dasatinib, she should be apprised of the potential hazard to the fetus. Fetal risks include skeletal abnormalities, reduced fetal weight, and increased rates of resorption, particularly in the first trimester. |
■ FDA Black Box Warning
Pulmonary arterial hypertension (PAH) may occur in patients receiving dasatinib, including cases of severe, life-threatening, or fatal PAH. Evaluate for signs and symptoms of cardiopulmonary disease prior to initiating therapy and during treatment. If PAH is confirmed, permanently discontinue dasatinib.
| Serious Effects |
["Hypersensitivity to dasatinib or any component of the formulation"]
| Precautions | ["Myelosuppression: Severe thrombocytopenia, neutropenia, and anemia may occur, particularly in advanced-phase CML or Ph+ ALL. Monitor complete blood counts regularly.","Hemorrhage: Severe central nervous system (CNS) and gastrointestinal hemorrhages, including fatalities, have occurred. Caution in patients requiring anticoagulation.","Fluid retention: Severe pleural effusions, pericardial effusions, and ascites may occur. Manage with diuretics or dose interruption/reduction.","QT prolongation: Dasatinib may prolong the QT interval. Monitor ECG and electrolytes in patients at risk.","Congestive heart failure and left ventricular dysfunction: Monitor for signs of cardiac dysfunction.","Pulmonary arterial hypertension (PAH): See black box warning. Discontinue if confirmed.","Hepatotoxicity: Elevations of transaminases and bilirubin may occur. Monitor hepatic function.","Tumor lysis syndrome: Ensure adequate hydration and correct uric acid levels prior to therapy."] |
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| Fetal Monitoring | Monitor complete blood counts (CBC) weekly for the first 2 months, then monthly, or as indicated. Monitor hepatic function (ALT, AST, bilirubin) and renal function (serum creatinine) periodically. Monitor for fluid retention (pleural effusion, pericardial effusion, pulmonary edema), pulmonary arterial hypertension, and QT interval prolongation. In pregnancy, monitor fetal growth and development with serial ultrasound examinations to detect anomalies if exposure occurs. Assess for signs of fetal distress or growth restriction. |
| Fertility Effects | Dasatinib may impair fertility in humans based on animal studies. In female rats, dasatinib caused ovarian atrophy and decreased fertility. In male rats, dasatinib caused testicular atrophy and decreased sperm count. The long-term effects on human fertility are unknown. Women of reproductive potential should use effective contraception during treatment and for at least 30 days after the last dose. |