Dasanix is a kinase inhibitor indicated for the treatment of
Newly diagnosed adults with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase.
Adults with chronic, accelerated or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including Imatinib.
Adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy
Dasanix 50 Tablet: Each film coated tablet contains Dasatinib Monohydrate INN 51.845 mg equivalent to Dasatinib 50 mg.
Side Effects
- Bloody or black tarry stools
- Body aches or pain
- Burning, tingling, numbness, or pain in the hands, arms, feet, or legs
- Chest pain
- Constipation
- Cough or hoarseness
- Difficulty with breathing
- Dizziness
- Ear congestion
- Fainting
- Fast, slow, or irregular heartbeat
- Fever or chills
- Full or bloated feeling
- Headache
- Loss of voice
- Lower back or side pain
- Painful or difficult urination
Please note that this is a general description, and specific medications may have unique side effects. Always consult with a healthcare professional for personalized information and guidance.
Mechanism of Action
Dasatinib drug, operating at nano molar concentrations, effectively inhibits various kinases, including:
- BCR-ABL
- SRC family (SRC, LCK, YES, FYN)
- c-KIT
- EPHA2
- PDGFRb
Modeling studies indicate Dasatinib’s versatile binding to multiple ABL kinase conformations. In vitro studies have demonstrated its efficacy in leukemic cell lines, addressing both Imatinib Mesylate-sensitive and -resistant variants. Notably, Dasatinib has proven effective against chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines with BCR-ABL overexpression.
Key findings include
Overcoming Imatinib Resistance: Dasatinib demonstrates the ability to overcome Imatinib resistance caused by BCR-ABL kinase domain mutations.
Alternate Signaling Pathways: Effective inhibition of alternate signaling pathways involving SRC family kinases (LYN, HCK) contributes to Dasatinib’s comprehensive action.
Multi-Drug Resistance: Dasatinib has shown promising results in overcoming multi-drug resistance gene overexpression.
Pharmacokinetics
Absorption
Dasatinib drug achieves peak plasma concentrations (Cmax) between 0.5 and 6 hours after oral administration. Its pharmacokinetics demonstrate dose-proportional increases in AUC and linear elimination characteristics within the dosage range of 15 mg to 240 mg/day. The overall mean terminal half-life of Dasatinib is 3 to 5 hours.
Distribution
Dasatinib is widely distributed in the body (apparent volume of distribution: 2505L). In human plasma, it binds strongly to proteins—about 96% for Dasatinib and 93% for its active metabolite. Notably, this binding remains consistent across concentrations ranging from 100 to 500 ng/mL.
Metabolism
Dasatinib drug undergoes extensive metabolism in humans, mainly through the cytochrome P450 enzyme 3A4. This enzyme, particularly CYP3A4, plays a key role in forming the active metabolite. Additionally, other enzymes such as flavin-containing monooxygenase 3 (FMO-3) and uridine diphosphate-glucuronosyltransferase (UGT) contribute to the formation of Dasatinib metabolites.
Elimination
After taking Dasatinib orally, most of it (85%) is eliminated through feces, while 4% is found in urine within 10 days. In urine, only 0.1% is unchanged Dasatinib, and in feces, it’s 19%. The remaining portion is in the form of metabolites.
Dosage and Administration
For chronic phase CML, start with 100 mg of Dasatinib once daily, taken by mouth. For accelerated phase CML, myeloid or lymphoid blast phase CML, or Ph+ ALL, the recommended starting dose is 140 mg once daily.
Take Dasatinib tablets whole; do not crush or cut them. You can take them with or without food, in the morning or evening.
Use in specific population
For nursing mothers, it’s advised to stop taking the drug. However, this decision should be made considering the importance of the drug for the mother.
For individuals with hepatic impairment, use Dasanix cautiously.
Warning and Precaution
Myelosuppression
- Dasanix treatment linked to severe (NCI CTC Grade 3 or 4) thrombocytopenia, neutropenia, and anemia.
- More common in advanced phase CML or Ph+ ALL compared to chronic phase CML.
Bleeding Related Events
- Dasatinib causes platelet dysfunction in vitro, leading to bleeding-related events.
Fluid Retention
- Dasatinib associated with fluid retention.
- Severe cases reported in up to 10% of patients in clinical trials.
QT Prolongation
- Use Dasanix drug cautiously in patients with or at risk of QT interval prolongation.
Pulmonary Arterial Hypertension (PAH)
- Dasanix may increase the risk of developing PAH.
- Risk persists after initiation, even beyond one year of treatment.
Embryo-fetal Toxicity
- Dasanix can cause fetal harm in pregnant women.
- Adverse outcomes reported in infants from mothers taking Dasatinib.
Drug Interaction
When coadministered with CYP3A4 inhibitors, caution is advised due to potential increased Dasatinib levels. If unavoidable, close monitoring is recommended, and a reduction in Dasatinib dose should be considered.
Conversely, with CYP3A4 inducers, there is a risk of decreased Dasatinib levels. In such cases, if coadministration cannot be avoided, adjusting the Dasatinib dose may be necessary.
The use of antacids concurrently with Dasatinib drug should be approached with care, as it may lead to reduced Dasatinib levels. To mitigate this, antacids should be administered at least 2 hours before or after Dasatinib, avoiding simultaneous intake.
Similarly, caution is advised when considering H2 antagonists/proton pump inhibitors alongside Dasatinib, as they may also decrease Dasatinib levels. In these situations, choosing antacids over H2 antagonists or proton pump inhibitors may be a preferable option.