FDA Approvals: Sprycel and Microcyn

The US Food and Drug Administration (FDA) has granted full approval to dasatinib tablets for the treatment of chronic myeloid leukemia in patients with resistance or intolerance to previous therapy including imatinib mesylate; and a hydrogel wound care dressing for moistening absorbent wound dressings and cleaning traumatic wounds, cuts, abrasions, and minor burns.

Dasatinib (Sprycel) Granted Full Approval for Chronic Myeloid Leukemia

On May 21, the FDA granted full approval for dasatinib tablets (Sprycel; Bristol-Myers Squibb Co) for the treatment of adults in all phases of chronic myeloid leukemia (CML; chronic, accelerated, or myeloid) with resistance or intolerance to previous therapy including imatinib mesylate (Gleevec; Novartis Pharmaceuticals Corp).

The product was initially granted initial approval for the treatment of CML under regulations governing new drugs for serious or life-threatening illnesses, based on hematologic and cytogenetic response rates in CML.

Full approval was based primarily on data from a phase 3 randomized, open-label, dose-optimization study, showing that use of dasatinib 100 mg/day (n = 167) yielded an estimated 80% progression-free survival rate (95% confidence interval [CI], 73% - 87%) and 91% overall survival rate (95% CI, 86% - 96%) according to Kaplan-Meier estimates at 2 years in patients with chronic-phase CML resistant or intolerant to imatinib therapy.

Results also showed that 63% of patients achieved major cytogenetic response (95% CI, 56% - 71%) during a median 22-month duration of treatment. Median time to major cytogenetic response was 2.9 months (95% CI, 2.8 months - 3.0 months), and 93% of patients maintained that response for 18 months (95% CI, 88% - 98%), based on Kaplan-Meier estimates.

"Sprycel helps to fulfill a need for second-line treatments for CML patients with resistance or intolerance to Gleevec. The two-year follow-up data further support the use of Sprycel as an important treatment option for this patient population," said Hagop Kantarjian, MD, chairman and professor of the Leukemia Department at MD Anderson Cancer Center in Houston, Texas, in a company news release.

The most commonly reported serious dasatinib-related adverse events in clinical trials encompassing more than 2100 patients included pleural effusion (11%), gastrointestinal tract bleeding (4%), febrile neutropenia (4%), dyspnea (3%), pneumonia (3%), pyrexia (3%), diarrhea (3%), infection (2%), congestive heart failure/cardiac dysfunction (2%), pericardial effusion (1%), and hemorrhage involving the central nervous system (1%). The most frequently reported adverse reactions (incidence, ≥ 20%) included myelosuppression, fluid retention events, diarrhea, headache, dyspnea, skin rash, fatigue, nausea, and hemorrhage.

The FDA warns that dasatinib is linked to a risk for myelosuppression potentially requiring dose interruption or reduction; complete blood counts should be performed weekly for the first 2 months and then monthly thereafter, or as clinically indicated.

Dasatinib is also associated with fluid retention that can be severe. Patients in whom symptoms suggestive of pleural effusion such as dyspnea or dry cough develop should be evaluated by chest radiographs; severe pleural effusion may require thoracentesis and oxygen therapy. Fluid retention is typically managed by supportive care measures that include diuretics or a short course of steroids. The FDA notes that patients 65 years and older are more likely to experience fluid retention events and dyspnea.

Because of the potential for QT interval prolongation, dasatinib should be used with caution in patients with hypokalemia, hypomagnesemia, congenital long QT syndrome, and in those taking anti-arrhythmic drugs, other medicinal products that lead to QT prolongation, and cumulative high-dose anthracycline therapy.

Dasatinib is metabolized hepatically by the cytochrome P 450 isoenzyme 3A4 (CYP 3A4), and concomitant use of strong enzyme inhibitors (eg, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) can increase the risk for toxicity. Coadministration of strong inducers (dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital) may necessitate dasatinib dose increases.

Because dasatinib is also a time-dependent inhibitor of the enzyme, caution is advised with concomitant use of CYP 3A4 substrates having a narrow therapeutic index (eg, alfentanil, astemizole, terfenadine, cisapride, cyclosporine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, or ergot alkaloids [ergotamine, dihydroergotamine]).

Long-term suppression of gastric acid secretion by use of histamine₂ antagonists or proton-pump inhibitors is likely to decrease dasatinib exposure and is not recommended; antacids should be administered at least 2 hours before or 2 hours after dosing with dasatinib.

Dasatinib previously was granted full approval for the treatment of patients with Philadelphia chromosome–positive acute lymphoblastic leukemia with resistance or intolerance to previous therapy.

Wound Care Dressing (Microcyn) Approved for Leg, Pressure, and Diabetic Ulcers

On May 3, the FDA approved a wound dressing (Microcyn; Oculus Innovative Sciences, Inc) for use under clinician supervision to moisten and lubricate absorbent wound dressings for traumatic wounds, cuts, abrasions, and minor burns. Specific indications include leg, pressure, and diabetic ulcers; and mechanically or surgically debrided skin.

According to the company Web site, the hydrogel product has demonstrated the ability to safely treat a wide range of pathogens, including antibiotic-resistant strains of bacteria (eg, methicillin-resistant Staphylococcus aureus), viruses, fungi, and spores. It is safe to use around the nose, mouth, and eyes and does not require mixing, dilution, or rinsing. The solution can be used directly on the wound or in combination with gauze, sponges, or other absorbent wound dressings.

The gel will be available both as a prescription and over-the-counter formulation beginning in June 2009 and is reimbursable by both Medicare and Medicaid.