Dasatinib


Dasatinib, sold under the brand name Sprycel among others, is a targeted therapy used to treat certain cases of chronic myelogenous leukemia and acute lymphoblastic leukemia. Specifically it is used to treat cases that are Philadelphia chromosome-positive. It is taken by mouth.
Common side effects include low white blood cells, low blood platelets, anemia, swelling, rash, and diarrhea. Severe side effects may include bleeding, pulmonary edema, heart failure, and prolonged QT syndrome. Use during pregnancy may result in harm to the baby. It is a tyrosine-kinase inhibitor and works by blocking a number of tyrosine kinases such as Bcr-Abl and the Src kinase family.
Dasatinib was approved for medical use in the United States and in the European Union in 2006. It is on the World Health Organization's List of Essential Medicines.

Medical uses

Dasatinib is used to treat people with chronic myeloid leukemia and people with acute lymphoblastic leukemia who are positive for the Philadelphia chromosome.
In the EU dasatinib is indicated for children with
and adults with
The most common side effects are infection, suppression of the bone marrow, headache, hemorrhage, pleural effusion, dyspnea, diarrhea, vomiting, nausea, abdominal pain, skin rash, musculoskeletal pain, tiredness, swelling in the legs and arms and in the face, fever.
Neutropenia and myelosuppression were common toxic effects. Fifteen people in the above-mentioned study developed pleural effusions, which was a suspected side effect of dasatinib. Some of these people required thoracentesis or pleurodesis to treat the effusions. Other adverse events included mild to moderate diarrhea, peripheral edema, and headache. A small number of people developed abnormal liver function tests which returned to normal without dose adjustments. Mild hypocalcemia was also noted, but did not appear to cause any significant problems. Several cases of pulmonary arterial hypertension were found in people treated with dasatinib.
On October 11, 2011, the U.S. Food and Drug Administration announced that 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. Symptoms of PAH may include shortness of breath, fatigue, and swelling of the body. In reported cases, people developed PAH after starting dasatinib, including after more than one year of treatment. Information about the risk was added to the Warnings and Precautions section of the Sprycel drug label.

Pharmacology

Dasatinib is an ATP-competitive protein tyrosine kinase inhibitor. The main targets of dasatinib are BCR/Abl, Src, c-Kit, ephrin receptors, and several other tyrosine kinases.

History

Dasatinib was developed by collaboration of Bristol-Myers Squibb and Otsuka Pharmaceutical Co., Ltd, and named for Bristol-Myers Squibb research fellow Jagabandhu Das, whose program leader says that the drug would not have come into existence had he not challenged some of the medicinal chemists' underlying assumptions at a time when progress in the development of the molecule had stalled.
Dasatinib was approved for used in the United States in June 2006 and in the European Union in November 2006
In October 2010, dasatinib was approved in the United States for the treatment of newly diagnosed adults with Philadelphia chromosome positive chronic myeloid leukemia in chronic phase.
In November 2017, dasatinib was approved in the United States for the treatment of children with Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase.
Approval was based on data from 97 pediatric participants with chronic phase CML evaluated in two trials—a Phase I, open-label, non-randomized, dose-ranging trial and a Phase II, open-label, non-randomized trial. Fifty-one participants exclusively from the Phase II trial were newly diagnosed with chronic phase CML and 46 participants were resistant or intolerant to previous treatment with imatinib. The majority of participants were treated with dasatinib tablets 60 mg/m2 body surface area once daily. Participants were treated until disease progression or unacceptable toxicity.

Cost

The Union for Affordable Cancer Treatment objected to the price of dasatinib, in a letter to the U.S. trade representative. The average wholesale price in the U.S. is $367 per day, twice the price in other high income countries. The price in India, where the average annual per capita income is $1,570, and where most people pay out of pocket, is Rs6627 a day. Indian manufacturers offered to supply generic versions for $4 a day, but, under pressure from the U.S., the Indian Department of Industrial Policy and Promotion refused to issue a compulsory license.
Bristol-Myers Squibb justified the high prices of cancer drugs with the high R&D costs, but the Union of Affordable Cancer Treatment said that most of the R&D costs came from the U.S. government, including National Institutes of Health funded research and clinical trials, and a 50% tax credit. In England and Wales, the National Institute for Health and Care Excellence recommended against dasatinib because of the high cost-benefit ratio.
The Union for Affordable Cancer Treatment said that "the dasatinib dispute illustrates the shortcomings of US trade policy and its impact on cancer patients"

Usual dosage

The usual dosage for chronic myelogenous leukemia is 100 mg orally once a day. A daily dose of 100 mg is also used for Philadelphia chromosome-positive acute lymphoblastic leukaemia. Oral absorption is not affected by food, and only 20% of unaltered dasatinib is found unaltered in faeces.

Brand names

In Bangladesh dasatinib is available under the trade name Dasanix by Beacon Pharmaceuticals.In India, It is marketed by brand name NEXTKI by EMCURE PHARMACEUTICALS