Medicine > All about Dasacine (Dasatinib) tablet

All about Dasacine (Dasatinib) tablet

Name of Medicine:- Dasacine

Product Ingredients:- Dasatinib

Chemical Formula:- C22H26ClN7O2S

Description:- Dasacine is an anti-cancer medicine marketed by Arechar Healthcare. It comprises Dasatinib and is used as a targeted therapy for the treatment of certain types of Blood Cancer

What is Dasacine?

Dasacine is an FDA-Approved anti-cancer drug. Its salt composition is Dasatinib 50mg. This medication is formulated as tablets (50mg/tablet) and is indicated for oral use only. It is a targeted therapy drug for certain types of cancers. Being a prescription medicine, it is used to treat Chronic Myelogenous Leukemia (CML) and Acute Lymphoblastic Leukemia (ALL). 

Clinical Relevance

Before using the medicine, make sure to read its indications carefully. Indications of medicine give a brief about its administration in different cases and its usages. Dasacine (Dasatinib) tablets are indicated for use in patients who are suffering from any of the following types of Blood Cancers. 

  • Chronic Myelogenous Leukemia (CML):- It is a very slow-progressing cancer in the Bone Marrow that causes an increase in the number of white blood cells.  

  • Acute Lymphoblastic Leukemia (ALL):- It is a type of Blood Cancer that develops when a Bone Marrow cell creates errors in its DNA. 

Specification

Dasacine is an anticancer formulation specifically for the treatment of patients who have Philadelphia chromosome-positive Blood Cancer. Philadelphia chromosome (abbreviated as the Ph chromosome) is an abnormality in chromosome 22 that is involved with chromosome 9 for an exchange of materials in a single cell of Bone Marrow. Such an abnormality gives rise to Leukemia. 

Clinical Pharmacology

Dasatinib is an oral multi-targeted kinase inhibitor. It belongs to the family of drugs known as Kinase Inhibitors. It is an inhibitor of breakpoint cluster region-abelson (BCR-ABL) and Src family kinases. Some of the aspects of the pharmacology of Dasatinib such as pharmacodynamics, results, metabolism, and mechanism of action are discussed below.

Pharmacokinetics

The evaluation of the pharmacokinetics of Dasatinib (Dasacine) has been done in 229 healthy subjects and 137 patients suffering from leukemia.

Absorption 

Dasatinib’s maximum plasma concentrations (Cmax) are noted between 0.5 and 6 hours (Tmax) followed by its oral administration. The overall mean terminal half-life of this compound is 3–5 hours. A study’s data of 54 healthy individuals given a single dose of Dasatinib of strength 100-mg, 30 minutes followed by consuming a high-fat meal resulted in a 14% increase in the mean AUC of Dasatinib. The observed food effects were not clinically relevant.

Distribution

In individuals, the apparent volume of distribution of Dasatinib was 2505 L, which makes it clear that the drug is extensively distributed in the extravascular space. Dasatinib binding in vitro was about 96% and its active metabolite to human plasma proteins in vitro was about 93%, with no notable concentration dependence over the range of 100–500 ng/mL.

Mechanism of action

Dasacine, comprising Dasatinib, works to inhibit a number of kinases such as BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ. On the basis of its modeling studies, Dasatinib is expected to bind to multiple conformations of the ABL kinase. In laboratory processes or Vitro, Dasatinib was active in leukemic cell lines and represented variants of imatinib mesylate sensitive and resistant disease. Dasatinib also inhibited the growth of leukemia cell lines including chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines overexpressing BCR-ABL. Dasatinib was also able to overcome the resistance by imatinib resulting from BCR-ABL kinase domain mutations, activation of alternate signaling pathways involving the SRC family kinases including LYN and HCK, and multi-drug resistance gene overexpression under the conditions of the assays.

Special Populations

The analyses of Pharmacokinetics of demographic data showed that there aren’t any clinically appropriate effects of age and gender on Dasacine’s pharmacokinetics. The pharmacokinetics of Dasatinib has not been evaluated in children. 

Clinical Trials

The introduction of tyrosine kinase inhibitors resulted in a notable change in the treatment of Chronic Myelogenous Leukemia (CML) because they tend to be superior to other treatments or therapies. The constant increase of effective therapeutic choices demonstrates a need for proper monitoring to decide the most-effective second-line treatment and the introduction of such therapy at the right moment.

The efficacy of dasatinib in the treatment of patients with CML or Ph+ALL who are resistant or intolerant to imatinib is evidently appropriate. The tolerability in the case of Dasatinib is satisfactory and most side effects that occurred due to Dasatinib were either mild or moderate and mostly reversible or treatable by monitoring, supportive care, or dose adjustments (increase or decrease).

The rates of Dasatinib discontinuation due to toxic adversities are low. There is no proper evidence of cross intolerance of Dasatinib with Imatinib. Therefore, Dasatinib is proved to be an effective and well-tolerated treatment option for second-line therapy to treat CML.

Drug Interactions

Drugs that may increase Dasatinib Plasma concentration 

CYP3A4 Inhibitors:- Dasacine (Dasatinib) is a CYP3A4 substrate. In a study, when patients having solid tumors were administered Dasatinib with Ketoconazole, it was observed that there was a notable increase in Dasatinib Cmax and AUC. Therefore, close monitoring is necessary for patients to avoid toxicity. If CYP3A4 Inhibitors can not be avoided, dose adjustments (reduction) shall be considered. 

Drugs that may decrease Dasatinib Plasma concentration

CYP3A4 Inducers:- When Dasacine was administered with a single evening dose of Rifampin 600mg, a decrease of about 81% and 82% in Dasatinib’s Cmax and AUC respectively was observed. If CYP3A4 Inducers can not be avoided with Dasatinib, dose adjustments (increase) shall be considered. 

Antacids:- In a study, when 24 healthy subjects were administered 30 mL of antacid (aluminum hydroxide/magnesium hydroxide) with a single dose of Dasatinib, a decrease of about 58% and 55% in Dasatinib’s Cmax and AUC respectively was observed. If antacid therapy can not be postponed or stopped during the treatment with Dasacine, dose adjustments (increase) shall be considered or the antacid should be administered at least 2 hours prior/later to the administration of Dasacine.

H2 Antagonists/Proton Pump Inhibitors:- In a study, when 24 healthy subjects were given Dasatinib 10 hours after the administration of Famotidine, a decrease of about 63% and 61% in Dasatinib’s Cmax and AUC respectively was observed. In a study, when 14 healthy subjects were given Dasatinib 22 hours after the administration of Omeprazole, a decrease of about 42% and 43% in Dasatinib’s Cmax and AUC respectively was observed. This is why the use of H2 Antagonists/Proton Pump Inhibitors with Dasacine is not recommended. 

Drug Category

Antineoplastic Agents:- Dasacine belongs to a class of drugs known as Antineoplastic Agents. Such agents are also referred to as chemotherapy, chemo, or cytotoxic drugs. These are used in the treatment of cancer.

Tyrosine Kinase Inhibitors:- These are the pharmaceutical drugs that inhibit tyrosine kinases. Such medication is also known as tyrphostin. Tyrosine Kinase Inhibitors activate many proteins by signal transduction cascades and are used to treat certain types of cancers. 

Immunosuppressive Agents:- Such medications are also known as immunosuppressants. These drugs are responsible for the inhibition or prevention of the immune system’s activity. Mostly, it is administered to patients undergoing organ transplants. 

Packaging and Storage

Dasacine (Dasatinib) is available in the form of tablets for oral use. Each bottle contains 60 tablets. Dasacine tablets should be stored at 68°F to 77°F (20°C to 25°C). Such medicines should be kept away from the reach of children and pets. Protect Dasacine tablets from direct light, heat, and moisture. Ask your doctor or pharmacist about the ways to dispose of unused or expired medicines. 

Dosage and Administration 

The initial recommended dose of Dasacine for chronic phase CML is 100mg. However, for patients of accelerated phase CML, Ph+ ALL, or myeloid or lymphoid blast phase CML, the recommended starting dose is 140mg. In both cases, Dasacine should be administered orally once a day, either in the morning or evening. It can be taken with or without food. The tablet should not be crushed, chewed, cut, or broken in any case. It should be swallowed with water. In clinical trials, Dasacine was administered to the patients until the two cases happened: disease progression and intolerance by the patient. Sometimes, dose adjustments (increase or decrease) may be needed as per the effects of medicine on the body, individual safety, and tolerance. 

Overdose 

Dasacine is highly associated with severe myelosuppression. People who administered more than the recommended dosage showed the symptoms of myelosuppression. Therefore, the patients of overdosage should be closely monitored for myelosuppression and should be given proper treatment accordingly. Regular monitoring of blood counts should be done. 

Adverse Reactions

Dasacine (Dasatinib) may cause some adverse reactions including Bleeding Related Events such as severe CNS hemorrhage, gastrointestinal hemorrhage, thrombocytopenia including fatalities. People who take medicines that work to inhibit platelet function or anticoagulants should administer Dasacine cautiously. 

This medication is associated with retention of fluid, severe ascites, and edema. Other adverse effects include dyspnea and dry cough. Such symptoms should be evaluated by chest X-ray. The cases of fluid retention can, however, be easily treated by short courses of steroids. 

Dasacine tablets may lead to Gastrointestinal Disorders such as frequent dyspepsia (discomfort or pain in the upper abdomen), anal fissure, ileus, pancreatitis, dysphagia (difficulty in swallowing), gastritis, and colitis. Other general disorders like malaise and temperature intolerance may occur. 

Skin and Subcutaneous Tissue Disorders may occur in some patients including photosensitivity reaction, nail disorder, urticaria, dermatitis, pigmentation disorder, dry skin, acne, and hyperhidrosis. Consult your physician straight away for immediate medical attention. 

Respiratory, Thoracic, and Mediastinal Disorders are also common in some patients administering Dasatinib. Such reactions include lung infiltration, pneumonitis, bronchospasm, asthma, and acute respiratory distress syndrome. 

Nervous System Disorders such as dysgeusia, syncope, convulsion, amnesia, transient ischemic attack, and tremor. Know more about such reactions on your nervous system from a pharmacist before the administration of this medication. 

In some patients, Hepatobiliary Disorders may occur and last long. Some of the frequent disorders are urinary frequency, renal failure, and tumor lysis syndrome. The infrequent reactions are proteinuria and hypersensitivity. 

Other common disorders that may occur after the administration of Dasacine are tinnitus and vertigo (Ear and Labyrinth Disorders);  insomnia, depression, anxiety, confusional state, and affect lability (Psychiatric Disorders); palpitations, angina pectoris, cardiomegaly, and myocardial infarction (Cardiac Disorders).

Warnings and Precautions

Pediatrics

The safety and efficacy of Dasacine in individuals<18 years of age have not been established. Therefore, it is not recommended for use in children. 

Geriatrics

Of the 511 patients in clinical studies of Dasatinib (dasatinib), 119 (23%) were over 65 years of age, while 13 (3%) were over 75 years of age. No overall differences in safety or efficacy were observed between these patients and younger patients. However, the greater sensitivity of some older individuals cannot be ruled out.

Pregnant Women

Dasacine tablets can cause fatal effects if administered to a pregnant female. It is not recommended for use during pregnancy. In non-clinical research, fetal toxicity was seen in rats and rabbits at plasma concentrations below those observed in humans receiving therapeutic doses of Dasatinib. Fetal death was observed in rats. In both rats and rabbits, the lowest doses of dasatinib tested (rat: 2.5 mg/kg/day and rabbit: 0.5 mg/kg/day) resulted in embryo-fetal toxicities. Such doses produced maternal AUCs of 44 ng•hr/mL and 105 ng•hr/mL in rabbits and rats, respectively. Embryo-fetal toxicities included a reduction in ossification (sternum; thoracic, lumbar, and sacral vertebrae; forepaw phalanges; pelvis; skeletal malformations at a number of sites (scapula, humerus, femur, radius, ribs, clavicle); and hyoid body), edema, and microhepatia.

Nursing Mothers

It is not known whether Dasacine is excreted in human milk. Women who are administering Dasatinib should not breast-feed.

Myelosuppression 

A few patients who are treated with Dasacine (Dasatinib) undergo reactions such as anemia, thrombocytopenia, and neutropenia. Therefore, regular monitoring of blood counts should be done. Several dose adjustments may also be needed in such patients. 

Bleeding-Related Events

In the patients of CML or Ph+ ALL, the most frequent site of bleeding was gastrointestinal. Some of the bleeding-related events were also associated with severe thrombocytopenia. In some patients, platelet dysfunction may occur with hemorrhage