FDA has approved dalbavancin (Dalvance—Durata Therapeutics), an I.V. antibiotic for the treatment of adults with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible gram-positive bacteria, including methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pyogenes.
First QIDP drug
Dalbavancin is the first drug to be designated a qualified infectious disease product (QIDP) under the Generating Antibiotic Incentives Now (GAIN) act of the FDA Safety and Innovation Act. Dalbavancin was granted the designation because it is an antibacterial or antifungal human drug intended to treat serious or life-threatening infections.
It is the first I.V. antibiotic approved for the treatment of ABSSSI with a two-dose regimen of 1,000 mg followed 1 week later by 500 mg, each administered over 30 minutes. (As this issue was going to press, FDA approved tedizolid phosphate [Sivextro—Cubist], the second QIDP antibiotic for the treatment of ABSSSI; see page 18.)
This “unique dosage regimen offers a new approach to treatment of these serious skin infections by allowing patients, health care professionals, and hospitals to move beyond the standard daily or twice-daily I.V. antibiotic infusions,” said Paul Edick, Chief Executive Officer of Durata Therapeutics, in a news release.
The majority of all skin and soft tissue infections in hospitalized patients are caused by streptococci and S. aureus, and approximately 59% of these S. aureus infections in the United States are estimated to be caused by MRSA. More than 4.8 million adults with ABSSSI were admitted to the hospital from 2005 through 2011, which included patients with cellulitis, erysipelas, wound infection, and major cutaneous abscess. Early and effective treatment of ABSSSI is critical to full patient recovery, and for certain patients may also help to avoid potentially lengthy and costly hospital stays, according to Durata’s news release.
Key clinical trials
Approval was based on two Phase III trials, DISCOVER 1 and DISCOVER 2 (Dalbavancin for Infections of the Skin COmpared to Vancomycin at an Early Response) of 1,289 adults with ABSSSI. Patients were randomly assigned to receive dalbavancin or vancomycin (Vancocin), another antibiotic drug. Results showed dalbavancin was as effective as vancomycin for treatment of ABSSSI.
The most common adverse effects were nausea, headache, and diarrhea. Of note, more participants in the dalbavancin group had elevations in one of their liver enzyme tests. The dalbavancin drug label provides recommendations on dosage adjustment in patients with renal impairment.
Dalbavancin will be shipped in the third quarter of 2014, according to the manufacturer.
Manufacturer: Durata Therapeutics
Drug class: Second-generation lipoglycopeptide
Indication: Treatment of acute bacterial skin and skin structure infections caused by designated susceptible strains of gram-positive microorganisms
Dosage: For a two-dose regimen, 1,000 mg followed 1 week later by 500 mg, each administered by I.V. infusion over 30 minutes; for patients with creatinine clearance less than 30 mL/min and not receiving regularly scheduled hemodialysis, dosage adjustment is 750 mg followed 1 week later by 375 mg.
Dalbavancin is supplied in single-use, clear glass vials containing sterile powder equivalent to 500 mg of anhydrous dalbavancin. It must be reconstituted with sterile water for injection and subsequently diluted with 5% dextrose injection to a final concentration of 1 mg/mL to 5 mg/mL."
Serious hypersensitivity (anaphylactic) and skin reactions have been reported with glycopeptide antibacterial agents, including dalbavancin; caution should be exercised in patients with known hypersensitivity to glycopeptides.
Of note: To reduce the development of drug-resistant bacteria and maintain the effectiveness of dalbavancin and other antibacterial drugs, dalbavancin should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria.
Advise patients that allergic reactions could occur, including serious ones requiring immediate treatment. Inform patients that antibacterial drugs, including dalbavancin, should be used only to treat bacterial infections, not viral infections. Inform patients that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy could decrease the effectiveness of treatment and increase the likelihood that bacteria will develop resistance and will not be treatable by dalbavancin and other antibacterial drugs in the future.
Inform patients that diarrhea is a common problem caused by antibacterial drugs and usually resolves when the drug is discontinued. Sometimes, frequent watery or bloody diarrhea may occur and may be a sign of a more serious intestinal infection. If severe watery or bloody diarrhea develops, patients should contact their primary care provider.