Company: Durata Therapeutics
Pharmacologic class: Lipoglycopeptide
Active ingredients: Dalbavancin 500 mg, per vial; lyophilized powder for intravenous (IV) infusion after reconstitution, preservative-free.
Indication: Acute bacterial skin and skin structure infections (ABSSSI) that have been caused by the following susceptible Gram-positive organisms: Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) as well as methicillin-sensitive S. aureus (MSSA), Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus anginosus Group (including the organisms Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus).
Pharmacology: Dalbavancin is a semisynthetic lipoglycopeptide that interferes with cell-wall synthesis by binding to the D-alanyl-D-alanine terminus of the stem pentapeptide in nascent cell-wall peptidoglycan, thus preventing cross-linking.
Dalbavancin is bactericidal in vitro against Staphylococcus aureus and Streptococcus pyogenes at concentrations similar to those sustained throughout therapy in humans treated according to the recommended dosage regimen.
Clinical trials: Adult patients with ABSSSI were enrolled in 2 phase 3, randomized, double-blind, double-dummy clinical trials of similar design (Trials 1 and 2). The intent-to-treat (ITT) population involved 1,312 randomized patients. Patients were in treatment for 2 weeks and were given either a 2-dose regimen of IV Dalvance (1,000 mg followed by 500 mg 1 week later) or IV vancomycin (1,000 mg or 15 mg/kg every 12 hours, with an option to switch to oral linezolid after 3 days). Dalvance-treated patients with creatinine clearance (CrCl) <30mL/min received 750 mg, followed 1 week later by 375 mg.
The primary endpoint of Trials 1 and 2 was the clinical response rate, with responders defined as patients who had no increase from baseline in lesion area 48 to 72 hours after initiation of therapy and who had a temperature consistently ≤37.6°C upon repeated measurement.
In Trial 1, 83.3% of the Dalvance group met the primary endpoint, as did 81.8% of the vancomycin/linezolid group (treatment difference: 1.5% [95% CI: −4.6, 7.9]).
In Trial 2, 76.8% of the Dalvance treatment group met the primary endpoint, compared with 78.3% of the vancomycin/linezolid treatment group (treatment difference: −1.5% [95% CI: −7.4, 4.6]).
A major secondary endpoint for these two trials involved the evaluation of the percentage of ITT patients achieving a ≥20% reduction in lesion area from baseline at 48 to 72 hours after initiation of therapy. In Trial 1, 89.9% of the Dalvance treatment group met the secondary endpoint, compared with 90.9% in the vancomycin/linezolid treatment group (treatment difference: −1.0% [95% CI: −5.7, 4.0]). In Trial 2, 87.6% of the Dalvance treatment group met the secondary endpoint, compared with 85.9% in the vancomycin/linezolid treatment group (treatment difference: 1.7% [95% CI: −3.2, 6.7]).
For more clinical trial data, see full labeling.
Adults: Give by IV infusion over 30 minutes. Initially 1,000 mg, followed by 500 mg 1 week later. Patients who have renal impairment (CrCl <30mL/min) and who are not receiving hemodialysis: initially 750 mg, followed by 375 mg 1 week later.
Children: Not established.
Warnings/Precautions: History of glycopeptide allergy. Discontinue if serious hypersensitivity or skin reactions occur. Risk of Clostridium difficile-associated diarrhea; discontinue if suspected or confirmed. Moderate or severe hepatic impairment (Child-Pugh Class B or C). Renal impairment (CrCl <30mL/min). Pregnancy (Category C). Nursing mothers.
Adverse reactions: Nausea, headache, diarrhea, vomiting, rash, pruritus; alanine transaminase (ALT) elevations, infusion-related reactions (e.g., Red-Man syndrome), C. difficile-associated diarrhea.
Note: Do not co-infuse with other medications or electrolytes. Avoid saline-based infusion solutions; may cause precipitation.
How supplied: Single-use vial—1
For more information, call (855) 387-2825 or visit www.Dalvance.com.