Dasatinib

Dasatinib
Details:
Dasatinib pharmacodynamically inhibits BCR-ABL kinase and SRC kinase activity along with several other selective oncogenic kinases, including c-KIT, ephrin receptor kinase (EPH), and PDGFb receptor . Dasatinib is a potent, sub-monopolar inhibitor of the BCR-ABL kinase with potency at 0.6-0.8 nm, thereby inhibiting the growth of cancer cells.
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Our Company
The company, located in Yanhai Industrial Park-one of the largest pharmaceutical industrial zones in China-covers an area of 35 acres. Through its three product segments-Guaiacol derivatives, Epichlorohydrin derivatives, and Iodine contrast media-Haizhou Pharm offers a portfolio of products and services globally, including Active Pharmaceutical Ingredients (API), intermediates, fine chemicals, and custom manufacturing services.

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With professional contract manufacturing project team and multi-functional workshops, the company is in long-term cooperation with famous global pharmaceutical enterprises, providing contract service under both GMP and none GMP conditions.

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Haizhou Pharm is ISO9001/14001 and OHSAS18001 approved, and ISO/OHSAS management philosophy deeps into whole process of the company.

Professional Contract Solutions
With professional contract manufacturing project team and multi-functional workshops, the company is in long-term cooperation with famous global pharmaceutical enterprises, providing contract service under both GMP and none GMP conditions.

 

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What is Dasatinib?

 

 

Dasatinib pharmacodynamically inhibits BCR-ABL kinase and SRC kinase activity along with several other selective oncogenic kinases, including c-KIT, ephrin receptor kinase (EPH), and PDGFb receptor . Dasatinib is a potent, sub-monopolar inhibitor of the BCR-ABL kinase with potency at 0.6-0.8 nm, thereby inhibiting the growth of cancer cells.

 

What Is Dasatinib Used For?

 

Dasatinib, a potent and versatile medication, has emerged as a significant player in the field of oncology, particularly in the treatment of specific types of leukemia. It was developed by Bristol-Myers Squibb and is primarily targeted at specific proteins involved in the growth of cancer cells. The drug has been approved for use in patients with chronic myeloid leukemia (CML) who are either newly diagnosed or have not responded to other treatments. Additionally, it is used for treating Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Research continues to explore its efficacy in other malignancies and its potential combination with other therapies to enhance treatment outcomes.

Dasatinib belongs to a class of drugs known as tyrosine kinase inhibitors (TKIs). These inhibitors target the BCR-ABL protein, an abnormal enzyme present in most patients with CML and Ph+ ALL. This enzyme results from a genetic abnormality called the Philadelphia chromosome. Normally, enzymes like BCR-ABL play a role in cellular functions such as growth and division. However, in cancer cells, the BCR-ABL enzyme is overactive, leading to uncontrolled cell proliferation.

Dasatinib works by blocking the activity of BCR-ABL and other related tyrosine kinases, thereby inhibiting the growth and proliferation of cancer cells. By targeting these abnormal enzymes, Dasatinib essentially halts the progression of the disease and can lead to the death of cancer cells. This mechanism not only makes Dasatinib effective in treating leukemia but also offers a targeted approach, reducing the impact on normal, healthy cells.

Administering Dasatinib is relatively straightforward, but it requires adherence to specific guidelines to ensure effectiveness and minimize side effects. Dasatinib is available in tablet form and is usually taken once daily, either in the morning or evening. The dosage may vary depending on the stage of the disease, the patient's overall health, and how well they tolerate the medication. It's crucial to follow the prescribed dosage and not to alter or discontinue the medication without consulting a healthcare provider.

Dasatinib tablets should be swallowed whole with water and can be taken with or without food. However, it is essential to avoid grapefruit and grapefruit juice as they can interfere with the absorption of the drug, potentially leading to higher levels in the bloodstream and an increased risk of side effects. The onset of action for Dasatinib can vary. Some patients may start to see improvements within a few weeks, while for others, it may take several months. Regular monitoring through blood tests and clinical assessments is necessary to evaluate the drug's effectiveness and adjust the dosage if needed.

While Dasatinib has proven to be a life-saving drug for many, it is not without its side effects. The severity and frequency of side effects can differ from one individual to another, depending on various factors such as the dosage, the duration of treatment, and the patient's overall health. Common side effects include nausea, diarrhea, headache, fatigue, and muscle pain. More serious side effects can involve low blood cell counts, which can increase the risk of infections, bleeding, and anemia. Some patients may also experience fluid retention, which can manifest as swelling in the hands, feet, or around the eyes, and in severe cases, fluid accumulation around the lungs or heart.

Dasatinib has specific contraindications. It should not be used in patients who are allergic to any of its components. Additionally, it is not recommended for use during pregnancy due to the potential risk of harm to the unborn baby. Women of childbearing age should use effective contraception while taking Dasatinib and for a period after discontinuing the drug. Breastfeeding is also not advised during treatment.

Drug interactions are a critical consideration when prescribing and taking Dasatinib. Certain medications can affect how Dasatinib works or increase the likelihood of side effects. For instance, drugs that influence the enzyme CYP3A4, such as ketoconazole, itraconazole, and ritonavir, can increase the level of Dasatinib in the blood, heightening the risk of adverse effects. Conversely, medications that induce CYP3A4, such as rifampin, phenytoin, and St. John's wort, can decrease Dasatinib levels, potentially reducing its efficacy.

Other medications that can interact with Dasatinib include antacids and H2 blockers like ranitidine and famotidine, which can reduce the absorption of Dasatinib if taken too closely together. It is recommended to take antacids at least two hours before or after Dasatinib. Additionally, drugs that prolong the QT interval, a specific measurement of heart rhythm, should be used with caution as Dasatinib itself can prolong the QT interval, increasing the risk of serious heart-related side effects.

 

Dosage Of The Drug Dasatinib
 

Depending on the treatment goal, Dasatinib will be used in different doses, specifically as follows:

For The Treatment Of Chronic Myeloid Leukemia (CML):

 

Starting dose: 100Mgx 1 time/ If a hematological or cytological response is not achieved, increase the dose to 140 mg once daily. The recommended starting dose for flare-ups, myeloid acceleration or lymphoid CML or Ph+ ALL is 140 mg/day. If hematologic or cytological response is not achieved, the dose may be increased to 180 mg once daily.

Dasatinib
Dasatinib

For the Treatment of Acute Lymphoblastic Leukemia Ph+ (ALL):

 

Initial dose: 140 Mg once daily if hematologic or cytological response is not achieved, the dose may be increased to 180 mg once daily. /day. Dose adjustment when toxicity occurs: if hematologic toxicity occurs, temporarily discontinue dasatinib, reduce dose or discontinue drug.

For Children on Ph+ CML-CP and Ph+ ALL:

 

Dasatinib is given orally once daily as a film-coated tablet. The dose should be recalculated every 3 months based on the change in body weight of the child. Tablets are not recommended for children weighing less than 10kg Powder for oral suspension should be used for this audience Recommended dose for children 10-20kg: 40 mg/day Recommended dose for children 20-30kg: 60 mg/day Recommended dose for children 30-45 kg: 70 mg/day Recommended dose for children at least 45 kg: 100 mg/day

Dasatinib

 

How Should I Take Dasatinib?

Take dasatinib exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

You may take dasatinib with or without food. Take the medicine at the same time each day.

Swallow the tablet whole and do not crush, chew, or break it.

Do not take a tablet that has been accidentally broken. The medicine from a crushed or broken tablet can be dangerous if it gets in your eyes, mouth, or nose, or on your skin. If this occurs, wash your skin with soap and water or rinse your eyes with water. Wear rubber gloves while handling a broken tablet or capsule. Ask your doctor or pharmacist how to safely dispose of the broken pill. A pregnant woman should not handle a broken pill.

Dasatinib can lower blood cells that help your body fight infections and help your blood to clot. Your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests.

 

Proteome Profiling Of Potential Dasatinib Of Affinity-Based
 

Protein kinases (PKs) play an important role in the development and progression of cancer by regulating cell growth, survival, invasion, metastasis, and angiogenesis. Dasatinib (BMS-354825), a dual Src/Abl inhibitor, is a promising therapeutic agent with oral bioavailability. It has been used for the treatment of imatinib-resistant chronic myelogenous leukemia (CML). Most kinase inhibitors, including Dasatinib, inhibit multiple cellular targets and do not possess exquisite cellular specificity.

 

Recent efforts in kinase research thus focus on the development of large-scale, proteome-wide chemical profiling methods capable of rapid identification of potential cellular (on- and off-) targets of kinase inhibitors. Most existing approaches, however, are still problematic and in many cases not compatible with live-cell studies. In this work, we have successfully developed a cell-permeable kinase probe (DA-2) capable of proteome-wide profiling of potential cellular targets of Dasatinib.

 

In this way, highly regulated, compartmentalized kinase–drug interactions were maintained. By comparing results obtained from different proteomic setups (live cells, cell lysates, and immobilized affinity matrix), we found DA-2 was able to identify significantly more putative kinase targets. In addition to Abl and Src family tyrosine kinases, a number of previously unknown Dasatinib targets have been identified, including several serine/threonine kinases (PCTK3, STK25, eIF-2A, PIM-3, PKA C-α, and PKN2).

 

They were further validated by pull-down/immunoblotting experiments as well as kinase inhibition assays. Further studies are needed to better understand the exact relevance of Dasatinib and its pharmacological effects in relation to these newly identified cellular targets. The approach developed herein should be amenable to the study of many of the existing reversible drugs/drug candidates.

 

Treatment For Dasatinib

 

 

Dasatinib is a dual Abl/Src tyrosine kinase inhibitor (TKI) designed as a prototypic short-acting BCR–ABL-targeted TKI that inhibits BCR–ABL with greater potency compared with imatinib, nilotinib, bosutinib, and ponatinib and has been shown to have potential immunomodulatory effects. Dasatinib is approved for the treatment of all phases of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant or intolerant to prior imatinib treatment and first-line treatment for CML in chronic phase.

 

 
Our Factory

 

The company, located in Yanhai Industrial Park, one of the largest pharmaceutical industrial zones in China, covers an area of 35 acres. Through its three product segments - Guaiacol derivatives, Epichlorohydrin derivatives and Iodine contrast media - Haizhou Pharm offers a portfolio of products and services globally, including Active Pharmaceutical Ingredients (API), Intermediates, fine chemicals and Customs manufacturing service.

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FAQ
 

Q: What is dasatinib used for?

A: Dasatinib is used to treat a certain type of chronic myeloid leukemia (CML; a type of cancer of the white blood cells) as a first treatment and in adults who can no longer benefit from other leukemia medications including imatinib (Gleevec) or in those who cannot take these medications because of side effects.

Q: Is dasatinib a blood thinner?

A: Dasatinib can lower blood cells that help your body fight infections and help your blood to clot. You may get an infection or bleed more easily.

Q: How long can you take dasatinib?

A: You take dasatinib for as long as it is working, and the side effects aren't too bad.

Q: What is the life expectancy of someone on dasatinib?

A: The 10-year overall survival, transformation-free survival, event-free survival, and failure-free survival rates were 89%, 95%, 86%, and 65%, respectively. Univariate analysis showed that the achievement of a complete MR was associated with improved overall survival.

Q: What foods should you avoid when taking dasatinib?

A: Dasatinib Food
Do not consume grapefruit or grapefruit juice during treatment with dasatinib.

Q: Can you stop taking dasatinib?

A: 14 Regarding second‐generation TKI, a Japanese prospective study demonstrated that approximately 49% of CML patients who achieved DMR for >1 year during second‐line dasatinib therapy could successfully discontinue treatment for >6 months,15 and attempts to discontinue nilotinib yielded similar observations.

Q: Does dasatinib affect the skin?

A: Anecdotal dermatologic side effects of dasatinib include perifollicular hyperkeratotic eruptions, an acneiform rash, hair depigmentation, vitiligo-like lesions, and panniculitis. A 23.3% incidence of rashes associated with dasatinib has been estimated. Most rashes were graded as mild, only 1.1% being high grade.

Q: What are the benefits of taking dasatinib?

A: DASATINIB contains Dasatinib, which belongs to the class of kinase inhibitors. It works by inhibiting the action of abnormal proteins that cause the multiplication of cancerous cells. This helps stop the abnormal growth of cancer cells and thus reduce the further spread to other parts of the body.

Q: When is the best time to take dasatinib?

A: Dasatinib comes as a tablet to take by mouth. It is usually taken once a day, with or without food. Take dasatinib at around the same time every day.

Q: What is the duration of dasatinib treatment?

A: The median duration of dasatinib for patients with CML-AP was 15 months (QD) or 13 months (BID) at the 5-year cutoff . At 7 years, the average daily dose of dasatinib was similar for patients enrolled based on hematologic criteria, clonal evolution, or prior diagnosis of CML-AP .

Q: Is dasatinib safe?

A: Dasatinib may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can rarely cause serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical attention right away.

Q: Can dasatinib cause high blood pressure?

A: (10/11/2011) FDA is warning the public that the leukemia drug Sprycel (dasatinib) may increase the risk of a rare, but serious condition in which there is abnormally high blood pressure in the arteries of the lungs (pulmonary arterial hypertension [PAH]).

Q: Do you need to take food with dasatinib?

A: Take this medicine by mouth with a glass of water. Follow the directions on the prescription label. You can take it with or without food.

Q: How long do you take dasatinib?

A: How long do you take it for? Sprycel is used as a long term treatment and in clinical trials has been taken for 5 years. You usually keep on taking it as long as: your tests show it is working well.

Q: What are the precautions for dasatinib?

A: SPRYCEL is associated with the following warnings and precautions: myelosuppression, bleeding-related events, fluid retention, cardiovascular toxicity, pulmonary arterial hypertension, QT prolongation, severe dermatologic reactions, tumor lysis syndrome, embryo-fetal toxicity, and hepatotoxicity.

Q: What is the function of dasatinib?

A: Description. Dasatinib is used to treat Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in adults and children. It is also used to treat Ph+ CML and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in adults after other medicines (eg, imatinib) or treatments did not work well.

Q: How long does it take for dasatinib to work?

A: Sprycel begins working shortly after you start taking it. Your body may begin to respond to the drug within 1 to 2 months. Some people who took Sprycel had a complete response (no sign of cancer cells in two bone marrow tests). This result was seen after about 3 months of treatment, in studies.

Q: What is the safety precaution for dasatinib?

A: Handle dasatinib with care. Just like when chemotherapy is given into the vein, this drug can be toxic, and exposure of the drug to others should be limited. Store dasatinib at room temperature (68°F--77°F) in a dry location away from light. Keep dasatinib out of reach of children and pets.

Q: When should I take dasatinib?

A: Dasatinib can be taken with or without a meal and should be taken consistently either in the morning or in the evening. Dasatinib should not be taken with grapefruit or grapefruit juice.

Q: What is the washout period for dasatinib?

A: Allow a washout period of approximately 1 week after the inhibitor is stopped before dasatinib dose is increased. Dosage with Hepatic Impairment: Dasatinib has not been studied in hepatic impairment within the indicated dosing range.

 

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