Drug Detail

Information about Sprycel

Generic Name	Dasatinib
IND	BMS-354825
Brand Name (US)	Sprycel
Manufacturer	Bristol-Myers Squibb
Drug Type	Tyrosine Kinase Inhibitor
Delivery	Oral
Approval Status	Approved for a non-GIST cancer
Indications	Imatinib-resistant CML
Overall Strategy	KIT Protein Based + Oncogenic Signal Path Based
Strategy	Block KIT + Block KIT Signal Path
Drug Category	KIT/PDGFRA inhibitor + SRC inhibitor

Approved for: Treatment of adults with chronic, accelerated, or myeloid or lymphoid blast phase chronic myeloid leukemia (CML) with resistance or intolerance to prior therapy including imatinib. Dastinib is noted in the NCCN guidelines as a therapy with activity in GIST (V2.2012), however, dasatinib is not FDA approved for GIST. A phase I combination trial of dasatinib and ipilimumab for Sarcoma and GIST started in 2012.
Targets: Dasatinib, at nanomolar concentrations, inhibits the following kinases: BCR-ABL, SRC family (SRC, LCK, YES, FYN), KIT, EPHA2, and PDGFRβ. Based on modeling studies, dasatinib is predicted to bind to multiple conformations of the ABL kinase. Dasatinib has been show to inhibit the PDGFRA exon 18 mutation, D842V. This mutation is insensitive to most other kinase inhibitors including imatinib and sunitinib, however, a more specific D842V inhibitor, crenolanib, is now in phase II trials (2011).
Dosage: 100 mg once daily for chronic phase CML or 140mg/day divided into two doses per day (BID) for accelerated phase CML, myeloid or lymphoid blast phase CML, or PH+ ALL.
Side effects: * The most frequently reported adverse reactions (reported in >20% of patients) included fluid retention events (37%), diarrhea (31%), headache (24%), skin rash (22%), nausea (22%), hemorrhage (21%), fatigue (21%), and dyspnea (20%)
* The most frequently reported serious adverse reactions included pleural effusion (9%), febrile neutropenia (4%), gastrointestinal bleeding (4%), pyrexia (3%), pneumonia (3%), dyspnea (3%), infection (2%), diarrhea (2%), congestive heart failure (2%), sepsis (1%), and pericardial effusion (1%)
* Grade 3/4 laboratory abnormalities in clinical studies in chronic phase CML included neutropenia (46%), thrombocytopenia (41%), anemia (18%), hypophosphatemia (10%), and hypocalcemia (2%)
* Grade 3/4 elevations of transaminase or bilirubin and Grade 3/4 hypocalcemia and hypophosphatemia were reported in patients with all phases of CML, but were reported with an increased frequency in patients with myeloid or lymphoid blast phase CML and Ph+ ALL
o Elevations in transaminase or bilirubin were usually managed with dose reduction or interruption
o Patients developing Grade 3/4 hypocalcemia during the course of SPRYCEL therapy often had recovery with oral calcium supplementation
o Proton pump inhibitors (PPI) interfere with the proper absorption of dasatinib, decreasing dasatinib levels by half.
This suggests that if you are taking one of these drugs to reduce stomach acid, it may reduce the amount of dasatinib in your blood by half. This should be a discussion point with your doctor if you are taking both.

See this link in the Links section below (Effect of a proton pump inhibitor . . . )

The following excerpt is from Wikipedia:

Proton pump inhibitors (or "PPI"s) are a group of drugs whose main action is a pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available today.

These drugs are utilized in the treatment of many conditions such as:

* Dyspepsia
* Peptic ulcer disease (PUD)
* Gastroesophageal reflux disease (GORD/GERD)
* Extraesophageal reflux disease
* Barrett's esophagus
* prevention of stress gastritis
* Gastrinomas and other conditions that cause hypersecretion of acid
* Zollinger-Ellison syndrome

Clinically used proton pump inhibitors:

* Omeprazole (brand names: Losec, Prilosec, Zegerid, ocid, Lomac, Omepral, Omez)
* Lansoprazole (brand names: Prevacid, Zoton, Inhibitol, Levant, Lupizole)
* Dexlansoprazole (brand name: Kapidex)
* Esomeprazole (brand names: Nexium, Esotrex)
* Pantoprazole (brand names: Protonix, Somac, Pantoloc, Pantozol, Zurcal, Pan)
* Rabeprazole (brand names: Rabecid, Aciphex, Pariet, Rabeloc. Dorafem: combination with domperidone