Dasatinib
FDA Drug Information • Also known as: Dasatinib, Phyrago, Sprycel
- Brand Names
- Dasatinib, Phyrago, Sprycel
- Dosage Form
- POWDER
- Product Type
- BULK INGREDIENT
Description
11 DESCRIPTION Dasatinib is a kinase inhibitor. The chemical name for dasatinib is N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide, monohydrate. The molecular formula is C 22 H 26 ClN 7 O 2 S
What Is Dasatinib Used For?
1 INDICATIONS AND USAGE Dasatinib tablets are indicated for the treatment of adult patients with Newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase. Chronic, accelerated or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib. Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy. Pediatric use information is approved for Bristol-Myers Squibb Company's Sprycel (dasatinib) tablets. However, due to Bristol-Myers Squibb Company's marketing exclusivity rights, this drug product is not labeled with that pediatric information. Dasatinib tablet is a kinase inhibitor indicated for the treatment of newly diagnosed adults with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase. ( 1 , 14 ) adults with chronic, accelerated or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib. ( 1 , 14 ) adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy. ( 1 , 14 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Chronic phase CML in adults: 100 mg once daily. ( 2 ) Accelerated phase CML, myeloid or lymphoid blast phase CML or Ph+ ALL in adults: 140 mg once daily. ( 2 ) Administer orally, with or without a meal. Do not crush, cut or chew tablets. ( 2 ) 2.1 Dosage of Dasatinib in Adult Patients The recommended starting dosage of dasatinib for chronic phase CML in adults is 100 mg administered orally once daily. The recommended starting dosage of dasatinib for accelerated phase CML, myeloid or lymphoid blast phase CML or Ph+ ALL in adults is 140 mg administered orally once daily. Tablets should not be crushed, cut or chewed; they should be swallowed whole. Dasatinib can be taken with or without a meal, either in the morning or in the evening. Pediatric use information is approved for Bristol-Myers Squibb Company's Sprycel (dasatinib) tablets. However, due to Bristol-Myers Squibb Company's marketing exclusivity rights, this drug product is not labeled with that pediatric information. 2.3 Dose Modification Strong CYP3A4 Inducers Avoid the use of concomitant strong CYP3A4 inducers and St. John's wort. If patients must be coadministered a strong CYP3A4 inducer, consider a dasatinib dose increase. If the dose of dasatinib is increased, monitor the patient carefully for toxicity [see Drug Interactions ( 7.1 )] . Strong CYP3A4 Inhibitors Avoid the use of concomitant strong CYP3A4 inhibitors and grapefruit juice. Recommend selecting an alternate concomitant medication with no or minimal enzyme inhibition potential, if possible. If dasatinib must be administered with a strong CYP3A4 inhibitor, consider a dose decrease to: 40 mg daily for patients taking dasatinib 140 mg daily. 20 mg daily for patients taking dasatinib 100 mg daily. 20 mg daily for patients taking dasatinib 70 mg daily. For patients taking dasatinib 60 mg or 40 mg daily, consider interrupting dasatinib until the inhibitor is discontinued. Allow a washout period of approximately 1 week after the inhibitor is stopped before reinitiating dasatinib. These reduced doses of dasatinib are predicted to adjust the area under the curve (AUC) to the range observed without CYP3A4 inhibitors; however, clinical data are not available with these dose adjustments in patients receiving strong CYP3A4 inhibitors. If dasatinib is not tolerated after dose reduction, either discontinue the strong CYP3A4 inhibitor or interrupt dasatinib until the inhibitor is discontinued. Allow a washout period of approximately 1 week after the inhibitor is stopped before the dasatinib dose is increased [see Drug Interactions ( 7.1 )] . Pediatric use information is approved for Bristol-Myers Squibb Company's Sprycel (dasatinib) tablets. However, due to Bristol-Myers Squibb Company's marketing exclusivity rights, this drug product is not labeled with that pediatric information. 2.4 Dose Escalation in Adults with CML and Ph+ ALL For adult patients with CML and Ph+ ALL, consider dose escalation to 140 mg once...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Myelosuppression [see Dosage and Administration ( 2.5 ) and Warnings and Precautions ( 5.1 )] . Bleeding-related events [see Warnings and Precautions ( 5.2 )] . Fluid retention [see Warnings and Precautions ( 5.3 )] . Cardiovascular toxicity [see Warnings and Precautions ( 5.4 )] . Pulmonary arterial hypertension [see Warnings and Precautions ( 5.5 )] . QT prolongation [see Warnings and Precautions ( 5.6 )] . Severe dermatologic reactions [see Warnings and Precautions ( 5.7 )] . Tumor lysis syndrome [see Warnings and Precautions ( 5.8 )] . Effects on growth and development in pediatric patients [see Warnings and Precautions ( 5.10 )]. Hepatotoxicity [see Warnings and Precautions ( 5.11 )] . Most common adverse reactions (≥ 15%) in patients receiving dasatinib as single-agent therapy included myelosuppression, fluid retention events, diarrhea, headache, skin rash, hemorrhage, dyspnea, fatigue, nausea and musculoskeletal pain. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to dasatinib administered as single-agent therapy at all doses tested in clinical studies (n=2,809), including 324 adult patients with newly diagnosed chronic phase CML, 2,388 adult patients with imatinib-resistant or -intolerant chronic or advanced phase CML or Ph+ ALL. The median duration of therapy in a total of 2,712 adult patients was 19.2 months (range 0 to 93.2 months). In a randomized trial in patients with newly diagnosed chronic phase CML, the median duration of therapy was approximately 60 months. The median duration of therapy in 1,618 adult patients with chronic phase CML was 29 months (range 0 to 92.9 months). The median duration of therapy in 1,094 adult patients with advanced phase CML or Ph+ ALL was 6.2 months (range 0 to 93.2 months). In the overall population of 2,712 adult patients, 88% of patients experienced adverse reactions at some time and 19% experienced adverse reactions leading to treatment discontinuation. In the randomized trial in adult patients with newly diagnosed chronic phase CML, drug was discontinued for adverse reactions in 16% of patients with a minimum of 60 months of follow-up. After a minimum of 60 months of follow-up, the cumulative discontinuation rate was 39%. Among the 1,618 patients with chronic phase CML, drug-related adverse reactions leading to discontinuation were reported in 329 (20.3%) patients; among the 1,094 patients with advanced phase CML or Ph+ ALL, drug-related adverse reactions leading to discontinuation were reported in 191 (17.5%) patients. Adverse reactions reported in ≥ 10% of adult patients and other adverse reactions of interest, in a randomized trial in patients with newly diagnosed chronic phase CML at a median follow-up of approximately 60 months are presented in Table 6. Adverse reactions reported in ≥ 10% of adult patients treated at the recommended dose of 100 mg once daily (n=165) and other adverse reactions of interest, in a randomized dose-optimization trial of patients with chronic phase CML resistant or intolerant to prior imatinib therapy at a median follow-up of approximately 84 months are presented in Table 8. Drug-related serious adverse reactions (SARs) were reported for 16.7% of adult patients in the randomized trial of patients with newly diagnosed chronic phase CML. Serious adverse reactions reported in ≥ 5% of patients included pleural effusion (5%). Drug-related SARs were reported for 26.1% of...
Drug Interactions
7 DRUG INTERACTIONS Strong CYP3A4 Inhibitors: Dose reduction may be necessary. ( 2.3 , 7.1 ) Strong CYP3A4 Inducers: Dose increase may be necessary. ( 2.3 , 7.1 ) Antacids: Avoid simultaneous administration. ( 7.1 ) H 2 Antagonists and Proton Pump Inhibitors: Avoid coadministration. ( 7.1 ) 7.1 Effect of Other Drugs on Dasatinib Strong CYP3A4 Inhibitors The coadministration with strong CYP3A inhibitors may increase dasatinib concentrations [see Clinical Pharmacology ( 12.3 )] . Increased dasatinib concentrations may increase the risk of toxicity. Avoid concomitant use of strong CYP3A4 inhibitors. If concomitant administration of a strong CYP3A4 inhibitor cannot be avoided, consider a dasatinib dose reduction [see Dosage and Administration ( 2.5 )] . Strong CYP3A4 Inducers The coadministration of dasatinib with strong CYP3A inducers may decrease dasatinib concentrations [see Clinical Pharmacology ( 12.3 )] . Decreased dasatinib concentrations may reduce efficacy. Consider alternative drugs with less enzyme induction potential. If concomitant administration of a strong CYP3A4 inducer cannot be avoided, consider a dasatinib dose increase. Gastric Acid Reducing Agents The coadministration of dasatinib with a gastric acid reducing agent may decrease the concentrations of dasatinib. Decreased dasatinib concentrations may reduce efficacy. Do not administer H 2 antagonists or proton pump inhibitors with dasatinib. Consider the use of antacids in place of H 2 antagonists or proton pump inhibitors. Administer the antacid at least 2 hours prior to or 2 hours after the dose of dasatinib. Avoid simultaneous administration of dasatinib with antacids.
Contraindications
4 CONTRAINDICATIONS None. None. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Based on limited human data, dasatinib can cause fetal harm when administered to a pregnant woman. Adverse pharmacologic effects including hydrops fetalis, fetal leukopenia and fetal thrombocytopenia have been reported with maternal exposure to dasatinib. Animal reproduction studies in rats have demonstrated extensive mortality during organogenesis, the fetal period and in neonates. Skeletal malformations were observed in a limited number of surviving rat and rabbit conceptuses. These findings occurred at dasatinib plasma concentrations below those in humans receiving therapeutic doses of dasatinib [see Data] . Advise a pregnant woman of the potential risk to a fetus. The estimated background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Clinical Considerations Fetal/Neonatal Adverse Reactions Transplacental transfer of dasatinib has been reported. Dasatinib has been measured in fetal plasma and amniotic fluid at concentrations comparable to those in maternal plasma. Hydrops fetalis, fetal leukopenia and fetal thrombocytopenia have been reported with maternal exposure to dasatinib. These adverse pharmacologic effects on the fetus are similar to adverse reactions observed in adult patients and may result in fetal harm or neonatal death [see Warnings and Precautions ( 5.1 , 5.3 )] . Data Human Data Based on human experience, dasatinib is suspected to cause congenital malformations, including neural tube defects and harmful pharmacological effects on the fetus when administered during pregnancy. Animal Data In nonclinical studies at plasma concentrations below those observed in humans receiving therapeutic doses of dasatinib, embryo-fetal toxicities were observed in rats and rabbits. Fetal death was observed in rats. In both rats and rabbits, the lowest doses of dasatinib tested (rat: 2.5 mg/kg/day [15 mg/m 2 /day] and rabbit: 0.5 mg/kg/day [6...
Overdosage
10 OVERDOSAGE Experience with overdose of dasatinib in clinical studies is limited to isolated cases. The highest overdosage of 280 mg per day for 1 week was reported in two patients and both developed severe myelosuppression and bleeding. Since dasatinib is associated with severe myelosuppression [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.1 )] , monitor patients who ingest more than the recommended dosage closely for myelosuppression and give appropriate supportive treatment. Acute overdose in animals was associated with cardiotoxicity. Evidence of cardiotoxicity included ventricular necrosis and valvular/ventricular/atrial hemorrhage at single doses ≥ 100 mg/kg (600 mg/m 2 ) in rodents. There was a tendency for increased systolic and diastolic blood pressure in monkeys at single doses ≥ 10 mg/kg (120 mg/m 2 ).
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Dasatinib Tablets, 20 mg are white to off-white, round, film-coated tablets, debossed with '1741' on one side and plain on the other side and are supplied as follows: NDC 70710-1741-6 in bottle of 60 tablets with child-resistant closure Dasatinib Tablets, 50 mg are white to off-white, oval, film-coated tablets, debossed with '1742' on one side and plain on the other side and are supplied as follows: NDC 70710-1742-6 in bottle of 60 tablets with child-resistant closure Dasatinib Tablets, 70 mg are white to off-white, round, film-coated tablets, debossed with '1743' on one side and plain on the other side and are supplied as follows: NDC 70710-1743-6 in bottle of 60 tablets with child-resistant closure Dasatinib Tablets, 80 mg are white to off-white, oblong, film-coated tablets, debossed with '1744' on one side and plain on the other side and are supplied as follows: NDC 70710-1744-3 in bottle of 30 tablets with child-resistant closure Dasatinib Tablets, 100 mg are white to off-white, oval, film-coated tablets, debossed with '1745' on one side and plain on the other side and are supplied as follows: NDC 70710-1745-3 in bottle of 30 tablets with child-resistant closure Dasatinib Tablets, 140 mg are white to off-white, round, film-coated tablets, debossed with '1746' on one side and plain on the other side and are supplied as follows: NDC 70710-1746-3 in bottle of 30 tablets with child-resistant closure Storage Dasatinib tablets should be stored at 20°C to 25°C (68ºF to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Handling and Disposal Dasatinib is an antineoplastic product. Follow special handling and disposal procedures. 1 Personnel who are pregnant should avoid exposure to crushed or broken tablets. Dasatinib tablets consist of a core tablet, surrounded by a film coating to prevent exposure of healthcare professionals to the active substance. The use of latex...
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.