Dasatinib

Description

Dasatinib is available in tablet form, with the following specifications:

• 20 mg tablets (NDC 70771-1901-6), supplied in bottles of 60 tablets.

• 50 mg tablets (NDC 70771-1902-6), supplied in bottles of 60 tablets.

• 70 mg tablets (NDC 70771-1903-6), supplied in bottles of 60 tablets.

• 80 mg tablets (NDC 70771-1904-3), supplied in bottles of 30 tablets.

• 100 mg tablets (NDC 70771-1905-3), supplied in bottles of 30 tablets.

• 140 mg tablets (NDC 70771-1906-3), supplied in bottles of 30 tablets.

All formulations are prescription-only and manufactured by Zydus.

Uses and Indications

Dasatinib is indicated for the treatment of patients with chronic myeloid leukemia (CML) in chronic phase, accelerated phase, or blast phase. Additionally, Dasatinib is indicated for the treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).

There are no specific teratogenic or nonteratogenic effects associated with Dasatinib mentioned in the provided data.

Dosage and Administration

Dasatinib is administered orally. The recommended dosages are as follows:

• Dasatinib 20 mg: Administer as prescribed by the healthcare professional.

• Dasatinib 50 mg: Administer as prescribed by the healthcare professional.

• Dasatinib 70 mg: Administer as prescribed by the healthcare professional.

• Dasatinib 80 mg: Administer as prescribed by the healthcare professional.

• Dasatinib 100 mg: Administer as prescribed by the healthcare professional.

• Dasatinib 140 mg: Administer as prescribed by the healthcare professional.

Healthcare professionals should ensure that patients adhere to the prescribed dosage and frequency as determined by their individual treatment plans.

Contraindications

There are no specified contraindications for the use of this product. Healthcare professionals should exercise clinical judgment when considering its use in patients with potential risk factors or underlying conditions.

Warnings and Precautions

There are currently no specific warnings or general precautions provided for the use of this medication. Healthcare professionals are advised to remain vigilant and consider the individual patient's health status and medical history when prescribing this treatment.

In the absence of detailed laboratory tests or monitoring parameters, it is essential for healthcare providers to exercise clinical judgment and conduct appropriate assessments based on the patient's condition. Regular follow-up and evaluation may be necessary to ensure the safe and effective use of the medication.

In case of any adverse reactions or unexpected symptoms, healthcare professionals should instruct patients to seek immediate medical assistance. Additionally, if a patient experiences significant changes in their health status, they should be advised to discontinue use and consult their healthcare provider promptly.

Side Effects

Patients receiving treatment may experience a range of adverse reactions, which can be categorized by seriousness and frequency.

Serious adverse reactions include myelosuppression, which encompasses thrombocytopenia, neutropenia, and anemia. Other serious effects noted are pleural effusion, pulmonary arterial hypertension, and cardiac arrhythmias, including atrial fibrillation and ventricular tachycardia. Hepatotoxicity, characterized by elevated liver enzymes, and severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis have also been reported.

Common adverse reactions observed in clinical trials include diarrhea, nausea, fatigue, headache, rash, vomiting, abdominal pain, anorexia, and fever. These reactions were frequently reported among participants and may require symptomatic management.

Less common adverse reactions include dizziness, insomnia, cough, dyspnea, peripheral edema, and skin discoloration. While these effects are not as prevalent, they may still impact patient comfort and quality of life.

Rare adverse reactions have been documented, including gastrointestinal perforation, hemorrhage, thrombotic events such as deep vein thrombosis and pulmonary embolism, pancreatitis, and renal impairment. These events, although infrequent, necessitate careful monitoring.

Postmarketing experience has revealed additional adverse reactions, including allergic reactions such as anaphylaxis, tumor lysis syndrome, and an increased risk of infections, particularly opportunistic infections.

Healthcare providers should monitor patients for signs of bleeding or infection and advise them to report any new or worsening symptoms promptly. This vigilance is essential to ensure patient safety and effective management of adverse reactions.

Drug Interactions

Dasatinib is subject to significant drug interactions that may alter its pharmacokinetics and pharmacodynamics.

CYP3A4 Inhibitors and Inducers Dasatinib is primarily metabolized by the CYP3A4 enzyme. Co-administration with strong CYP3A4 inhibitors, such as ketoconazole, itraconazole, and ritonavir, may lead to increased plasma concentrations of dasatinib. This elevation in plasma levels could enhance the risk of adverse effects associated with dasatinib. Therefore, it is advisable to monitor patients closely for signs of toxicity and consider dosage adjustments as necessary.

Conversely, strong CYP3A4 inducers, including rifampin, phenytoin, and carbamazepine, may decrease dasatinib plasma concentrations, potentially reducing its therapeutic efficacy. In such cases, careful monitoring of the patient's response to dasatinib is recommended, and dosage adjustments may be required to maintain effective drug levels.

Additionally, other substances that may influence dasatinib metabolism include St. John's Wort and certain anticonvulsants. The impact of these agents on dasatinib should be evaluated, and appropriate monitoring or adjustments should be made.

Laboratory Test Interference Dasatinib has been associated with thrombocytopenia, which may lead to decreased platelet counts in laboratory tests. Clinicians should be aware of this potential effect when interpreting platelet levels in patients receiving dasatinib therapy.

Furthermore, dasatinib may also influence liver function tests, specifically alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Regular monitoring of liver function is recommended to detect any significant changes that may necessitate intervention.

Packaging & NDC

The table below lists all NDC Code configurations of Dasatinib, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Pediatric use of Dasatinib has not been established, and safety and effectiveness in pediatric patients have not been determined. Therefore, Dasatinib is not recommended for use in children.

Geriatric Use

Elderly patients may be treated with Dasatinib; however, there are no specific recommendations or considerations for geriatric use outlined in the prescribing information. Healthcare providers should exercise caution when prescribing this medication to geriatric patients, as individual responses may vary.

It is advisable to monitor elderly patients closely for any potential adverse effects and to consider the overall health status and comorbidities that may influence treatment outcomes. While no dosage adjustments are specified for this population, clinicians should remain vigilant and adjust treatment as necessary based on the patient's clinical response and tolerability.

Pregnancy

Dasatinib is contraindicated in pregnancy due to the potential risk to the fetus associated with its use. Healthcare professionals should advise pregnant patients of the potential dangers and consider alternative treatment options. Women of childbearing potential should be informed of the risks and advised to use effective contraception during treatment with dasatinib to prevent pregnancy.

Lactation

There are no specific warnings or recommendations regarding nursing mothers or lactation mentioned in the provided drug insert for Dasatinib. Therefore, the effects of Dasatinib on breastfed infants and its excretion in human milk remain undetermined. Healthcare professionals should consider the potential risks and benefits when prescribing Dasatinib to lactating mothers.

Renal Impairment

Patients with renal impairment do not require specific dosage adjustments or recommendations as outlined in the prescribing information. Additionally, there are no special monitoring or safety considerations indicated for patients with reduced kidney function.

Hepatic Impairment

Dasatinib is primarily metabolized in the liver; therefore, caution should be exercised when administering this medication to patients with hepatic impairment. In such patients, a reduced dose of dasatinib may be necessary to mitigate the risk of adverse effects associated with compromised liver function.

Regular monitoring of liver function tests is recommended for patients receiving dasatinib, particularly for those with pre-existing liver conditions. It is important to note that the safety and efficacy of dasatinib in patients with severe hepatic impairment have not been established, and thus, careful consideration should be given when treating this population.

Overdosage

In cases of dasatinib overdosage, clinical experience in humans is limited. However, the most frequently observed adverse reactions in patients who have received doses exceeding the recommended levels include thrombocytopenia, neutropenia, and diarrhea.

Monitoring is essential in the event of an overdose, with healthcare professionals advised to observe patients for any signs and symptoms of toxicity. As there is no specific antidote available for dasatinib overdose, management should focus on symptomatic and supportive care to address the adverse effects experienced by the patient.

Nonclinical Toxicology

Animal studies have demonstrated that dasatinib administration during pregnancy is associated with adverse developmental outcomes. However, no teratogenic effects were observed in these studies. The findings suggest that while dasatinib does not induce teratogenicity, it may still lead to other developmental issues in the offspring.

Postmarketing Experience

Postmarketing experience has identified several adverse reactions associated with the use of the product. Reports have included pulmonary arterial hypertension, pleural effusion, and pericardial effusion. Severe skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, have also been documented.

Gastrointestinal bleeding, including instances that were fatal, has been reported. Additionally, cases of hepatotoxicity, characterized by elevated liver enzymes and liver failure, have been observed. Cardiac events, including arrhythmias and heart failure, have been noted in the postmarketing data.

Thrombotic events, such as deep vein thrombosis and pulmonary embolism, have been reported, along with various infections, including opportunistic infections. Furthermore, cases of pancreatitis and hematologic abnormalities, including thrombocytopenia and leukopenia, have been documented.

Patient Counseling

Patients should be advised to take dasatinib exactly as prescribed by their healthcare provider. It is important for patients to understand that dasatinib can cause serious side effects, including low blood cell counts, bleeding problems, and heart problems. They should be instructed to report any signs of infection, unusual bruising or bleeding, or symptoms of heart problems, such as chest pain or shortness of breath, to their healthcare provider immediately.

Patients should also be advised to avoid grapefruit and grapefruit juice during treatment with dasatinib, as these can increase the levels of the medication in the blood. Additionally, patients should be informed that dasatinib may cause fertility issues and should discuss any concerns regarding this with their healthcare provider.

It is essential for patients to inform their healthcare provider of any other medications they are taking, including over-the-counter drugs and supplements, as interactions may occur. Patients should be instructed that dasatinib can be taken with or without food, but they should maintain a consistent routine regarding food intake.

Finally, patients should be advised to keep all scheduled appointments for blood tests and follow-up visits to monitor their response to treatment and any potential side effects.

Storage and Handling

The product is supplied in a container that must be kept tightly closed to maintain integrity. It should be stored at a temperature range of 20°C to 25°C (68°F to 77°F), with permissible excursions between 15°C to 30°C (59°F to 86°F). It is essential to protect the product from light to prevent degradation. Any unused portion should be discarded after the expiration date to ensure safety and efficacy.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Dasatinib as submitted by Zydus Lifesciences Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)