DALVANCE Rx
Pharmacological Class:
Lipoglycopeptide.

Active Ingredient(s):
Dalbavancin 500mg; per vial; lyophilized pwd for IV infusion after reconstitution; preservative-free.

Company
Durata Therapeutics

Indication(s):
Acute bacterial skin and skin structure infections (ABSSSI) caused by the following susceptible Gram (+) organisms: Staphylococcus aureus (including MRSA and MSSA), Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus anginosus Group (including Streptococcus anginosus, Streptococcus intermedius, 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 treatment in humans treated according to the recommended dosage regimen.

Clinical Trials:
Adult patients with acute bacterial skin and skin structure infections (ABSSSI) were enrolled in two 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 two weeks and were given either a 2-dose regimen of IV Dalvance (1000mg followed by 500mg one week later) or IV vancomycin (1000mg or 15mg/kg every 12 hours, with an option to switch to oral linezolid after 3 days).

The primary endpoint of Trials 1 and 2 was the clinical response rate where responders were defined as patients who had no increase from baseline in lesion area 48–72 hours after initiation of therapy, and had a temperature consistently ≤37.6°C upon repeated measurement.

In Trial 1, 83.3% of the Dalvance treatment group met the primary endpoint as compared to 81.8% of the Vancomycin/Linezolid treatment 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 as compared to 78.3% of the Vancomycin/Linezolid treatment group (treatment difference ?1.5% [95% CI: ?7.4, 4.6]).

A major secondary endpoint in these two trials eva luated the percentage of ITT patients achieving a ≥20% reduction in lesion area from baseline at 48–72 hours after initiation of therapy.

In Trial 1, 89.9% of the Dalvance treatment group met the secondary endpoint as compared to 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 as compared to 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.

Legal Classification:
Rx

Adults:
Give by IV infusion over 30 minutes. Initially 1000mg, followed by 500mg one week later. Renal impairment (CrCl <30mL/min) and who are not receiving hemodialysis: initially 750mg followed by 375mg one 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 Reaction(s)
Nausea, headache, diarrhea, vomiting, rash, pruritus; ALT elevations, infusion-related reactions (eg, Red-Man Syndrome), C. difficile-associated diarrhea.

How Supplied:
Single-use vial—1

LAST UPDATED:
9/9/2014