Drug interactions - summary-

+ Dasatinib

Antacids
admin of alumininium hydroxide/magnesium hydroxide 2 hours prior to a single dose increased. Cmax when doses given concomittantly. Give antacids 2 hours before or after disatinib

Azole antifungals eg. ketoconazole/itraconazole -
azole antifungals decrease metabolism and increase concentration of dasatinib.
Should be avoided

CYP3A4 inducers eg. carbamazepine, dexamethasone, phenobarbital, phenytoin-
CYP3A4 may decrease dasatinib plasma concentration

H2 blockers eg famotidine/proton pump inhibitors eg omeprazole
long term suppression of gastric acid secretion likely to dasatinib exposure.
Concomittant use of H2 blockers or proton pump inhibitors not recommended

Macrolides eg clarithromycin, erythromycin -
macrolides decrease metabolism and increase concentration of dasatinib.
Should be avoided

Nefazodone
nefazodone decrease metabolism and increase concentration of dasatinib
Should be avoided

Protease inhibitors eg, arazanavir, indinavir, nelfinavir, ritonavir, saquinavir-
ptrotease inhibitors decrease metabolosm and increase concentration of dasatinib
should be avoided

Rifampin
coadmin of rifampin decreaced  mean Cmax and AUC  of dasatinib

St Johns wart -
coadmin may decrease dastainib plasma concentration. Avoid concurrent use

Telithromycin
Telithromycin may decrease metabolism and increase concentration of dasatinib
Should be avoided

Dasatinib +

CYP3A4 substrates eg. alfentanil, astemizole, cisapride, cyclosporine, ergot alkaloids, fentanyl , pimozide, quinidine, sirolimus, terfenadine
CYP3A4 substrates may have their plasma concentration altered by dasatinib

Simvasatin -
Cmax and AUC  of simavastatin were increased when administered with a single dose
of dasatinib

Acute lymphoblastic leukemia ( ALL )
Chronic myeloid leukemia ( CML )

Most frequently reported adverse reactions-
fluid retension, bleeding reactions,  reactions including abdominal pain, nausea and vomiting

Most frequently reported serious adverse reactions-
anemia, cardiac failure, diarrhea, dyspnea, febrile neutropenia, GI bleeding, pleural effusion,
pneumonia, pyrexia and thrombocytopenia

Cardiovascular -   arrhythmia  10%   chest pain  12%  congestive heart failure 3%
                                pericardial efusion  3%

CNS-                     asthenia   18%  dizziness 12%   fatigue   37%    headache  38%
                              neuropathy  12%

Dermatologic -   pruritus  10%    skin rash  32%

GI                         abdominal distention 10%   abdominal pain  23%  anorexia   18%
                             constipation 12%       diarrhea   46%       GI bleeding  12%
                             mucosal inflammation  15%       nausea  32%     vomiting 20%

Metabolic/nutrional -   fluid retention  48%   generalized edema  4%
                                      other fluid retention  12%   superficial edema  34%

Musculoskeletal -  arthagia  16%   musculoskeletal pain  35%  myalgia  10%

Respiratory -   cough   26%  dyspnea 30%   plural effusion  20%
                         pneumonia   10%    pulmonary edema 3% 
                         upper respiratory tract infection/ inflammation 25%

Miscellaneous -    chills  10%  febrile  neureopenia  7% hemorrhage 38%
                                infections 32%      pain  24%   pyrexia   36%
                                weight decreased 12%   weight increased 9%   

Special Precautions/Warnings-

Hemorrhage - Dasatinib caused platelet dysfunction . Severe CNS hemorrhage
including fatalites reported.
Excercise caution if patients are required to take medications that inhibit platelet function
or anticoagulants

Fluid retention-dasatinib is associated with fluid retention.
evaluate patients who develop symptoms suggestive of pleural effusionsuch as dyspnea
or dry cough by chest x-ray. Severe pleural effusion may require thoracentesis and oxygen
 therapy.

Fluid retention were typically managed by supportive care measures that included diuretics or short course of steroids

QT prolongation- administer dasatinib with caution to patients who have or may develop
prolongation of QTc. These include patients with hypokalemia or hypomagnesemia,
patients with congenital long QT syndrome, patients taking antiarrhthmics medicines or
other medicines that lead to QT prolongation

Pregnancy- dasatinib is not recommended for use in women who are pregnant or
contemplating pregnancy

Lactation- women who are taking dasatinib should not breast feed

Children- safety and efficacy of disatinib in patients younger than 18 years of age have not
been established

Monitoring- perform complete blood cell counts weekly for the first 2 months and then
monthly therafter

Indication-

Acute lymphoblastic leukemia ( ALL )
Chronic myeloid leukemia ( CML )

Dosage-
Tablets should not be crushed or cut. They should be swallowed whole.
May be taken with or without a meal

ALL - 140mg/day administered orally in 2 divided doses ( 70mg twice daily )
1 in the morning and 1 in the evening with or without meal

CML -  accelrated /myeloid/lymphoid blast phase-
140mg/day administered orally in 2 divided doses ( 70mg twice daily )
1 in the morning and 1 in the evening with or without meal

Chronic phase - 100mg administered orally once daily either in the morning or
evening

1. Advice patient not to crush or cut distanib , they should be swallowed whole.

2. Advice patient that  dasatinib contains lactose monohydrate 189mg in 140mg daily dose

May be taken with or without a meal

Pregnancy-
Dasatinib is not recommended for use in women who are pregnant or
contemplating pregnancy

Lactation-                                                                                                                              Women who are taking dasatinib should not breast feed

Children-
Safety and efficacy of dasatinib in patients younger than 18 years of age have not
been established