Sprycel

Sprycel - General Information

Sprycel is an oral dual BCR/ABL and Src family tyrosine kinases inhibitor approved for use in patients with chronic myelogenous leukemia (CML). The main targets of Sprycel, are BCRABL, SRC, Ephrins and GFR.

Pharmacology of Sprycel

Sprycel is an oral dual BCR/ABL and Src family tyrosine kinase inhibitor

Sprycel for patients

Sprycel Interactions

Drugs that may increase dasatinib plasma concentrations

CYP3A4 Inhibitors: Dasatinib is a CYP3A4 substrate. Concomitant use of SPRYCEL and drugs that inhibit CYP3A4 (eg, ketoconazole, itraconazole, erythromycin, clarithromycin, ritonavir, atazanavir, indinavir, nefazodone, nelfinavir, saquinavir, telithromycin) may increase exposure to dasatinib and should be avoided. In patients receiving treatment with SPRYCEL, close monitoring for toxicity and a SPRYCEL dose reduction should be considered if systemic administration of a potent CYP3A4 inhibitor cannot be avoided.

CYP3A4 Inducers: Drugs that induce CYP3A4 activity may decrease dasatinib plasma concentrations. In patients in whom CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital) are indicated, alternative agents with less enzyme induction potential should be used. If SPRYCEL must be administered with a CYP3A4 inducer, a dose increase in SPRYCEL should be considered.

St. John's wort (Hypericum perforatum) may decrease SPRYCEL plasma concentrations unpredictably. Patients receiving SPRYCEL should not take St. John's wort.

Antacids: Nonclinical data demonstrate that the solubility of dasatinib is pH dependent. Simultaneous administration of SPRYCEL with antacids should be avoided. If antacid therapy is needed, the antacid dose should be administered at least 2 hours prior to or 2 hours after the dose of SPRYCEL.

H₂ Blockers/Proton Pump Inhibitors: Long-term suppression of gastric acid secretion by H₂ blockers or proton pump inhibitors (eg, famotidine and omeprazole) is likely to reduce dasatinib exposure. The concomitant use of H₂ blockers or proton pump inhibitors with SPRYCEL is not recommended. The use of antacids should be considered in place of H₂ blockers or proton pump inhibitors in patients receiving SPRYCEL therapy.

CYP3A4 Substrates: Dasatinib is a time-dependent inhibitor of CYP3A4. Therefore, CYP3A4 substrates known to have a narrow therapeutic index such as alfentanil, astemizole, terfenadine, cisapride, cyclosporine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, or ergot alkaloids (ergotamine, dihydroergotamine) should be administered with caution in patients receiving SPRYCEL.

There are currently no clinical studies with SPRYCEL in patients with impaired liver function (clinical studies have excluded patients with ALT and/or AST >2.5 times the upper limit of the normal range and/or total bilirubin >2 times the upper limit of the normal range). Metabolism of dasatinib is mainly hepatic. Caution is recommended in patients with hepatic impairment.

There are currently no clinical studies with SPRYCEL in patients with impaired renal function (clinical studies have excluded patients with serum creatinine concentration >1.5 times the upper limit of the normal range). Dasatinib and its metabolites are minimally excreted via the kidney. Since the renal excretion of unchanged dasatinib and its metabolites is <4%, a decrease in total body clearance is not expected in patients with renal insufficiency.

Sprycel Contraindications

No known contraindications.

Additional information about Sprycel

Sprycel Indication: For the treatment of adults with chronic, accelerated, or myeloid or lymphoid blast phase chronic myeloid leukemia with resistance or intolerance to prior therapy. Also indicated for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia with resistance or intolerance to prior therapy.
Mechanism Of Action: Sprycel, at nanomolar concentrations, inhibits the following kinases: BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ. Based on modeling studies, dasatinib is predicted to bind to multiple conformations of the ABL kinase. In vitro, dasatinib was active in leukemic cell lines representing variants of imatinib mesylate sensitive and resistant disease. Sprycel inhibited the growth of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines overexpressing BCR-ABL. Under the conditions of the assays, dasatinib was able to overcome imatinib resistance resulting from BCR-ABL kinase domain mutations, activation of alternate signaling pathways involving the SRC family kinases (LYN, HCK), and multi-drug resistance gene overexpression.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Dasatinib
Synonyms: Not Available
Drug Category: Protein Kinase Inhibitors
Drug Type: Small Molecule; Approved

Other Brand Names containing Dasatinib: Sprycel;
Absorption: Not Available
Toxicity (Overdose): Acute overdose in animals was associated with cardiotoxicity.
Protein Binding: 96%
Biotransformation: Dasatinib is extensively metabolized in humans, primarily by the cytochrome P450 enzyme 3A4
Half Life: The overall mean terminal half-life of dasatinib is 3-5 hours.
Dosage Forms of Sprycel: Tablet Oral
Chemical IUPAC Name: N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide
Chemical Formula: C22H26ClN7O2S
Dasatinib on Wikipedia: https://en.wikipedia.org/wiki/Dasatinib
Organisms Affected: Humans and other mammals