Dalbavancin Injection

Dalbavancin injection is used in adults to treat skin infections caused by certain types of bacteria. Dalbavancin is in a class of medications called lipoglycopeptide antibiotics. It works by killing bacteria. Antibiotics will not kill viruses that can cause colds, flu, or other infections.

Keep all appointments with your doctor.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

DALVANCE is supplied in single-use, clear glass vials containing sterile powder (white/off-white to pale yellow) equivalent to 500 mg of anhydrous dalbavancin.

DALVANCE is contraindicated in patients with known hypersensitivity to dalbavancin. No data are available on cross-reactivity between dalbavancin and other glycopeptides, including vancomycin.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of DALVANCE cannot be directly compared to rates in the clinical trials of another drug and may not reflect rates observed in practice.

Adverse Reactions in Clinical Trials

Adverse reactions were evaluated for 1778 patients treated with DALVANCE and 1224 patients treated with comparator antibacterial drugs in seven Phase 2 and Phase 3 clinical trials. A causal relationship between study drug and adverse reactions was not always established. The median age of patients treated with DALVANCE was 47 years, ranging between 16 and 93 years old. Patients treated with DALVANCE were predominantly male (60%) and Caucasian (78%).

Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation

Serious adverse reactions occurred in 109/1778 (6.1%) of patients treated with DALVANCE and in 80/1224 (6.5%) of patients treated with comparator. DALVANCE was discontinued due to an adverse reaction in 53/1778 (3%) patients and the comparator was discontinued due to an adverse reaction in 35/1224 (2.8%) patients.

Most Common Adverse Reactions

The most common adverse reactions in patients treated with DALVANCE were nausea (5.5%), headache (4.7%), and diarrhea (4.4%). The median duration of adverse reactions was 4.0 days in both treatment groups.

Table 1 lists selected adverse reactions occurring in more than 2% of patients treated with DALVANCE in clinical trials.

The following selected adverse reactions were reported in DALVANCE treated patients at a rate of less than 2% in these clinical trials:

Blood and lymphatic system disorders: anemia, hemorrhagic anemia, leucopenia, neutropenia, thrombocytopenia, petechiae, eosinophilia, thrombocytosis

Gastrointestinal disorders: gastrointestinal hemorrhage, melena, hematochezia, abdominal pain

General disorders and administration site conditions: infusion-related reactions

Hepatobiliary disorders: hepatotoxicity

Immune system disorders: anaphylactoid reaction

Infections and infestations: Clostridium difficile colitis, oral candidiasis, vulvovaginal mycotic infection

Investigations: hepatic transaminases increased, blood alkaline phosphatase increased, international normalized ratio increased

Metabolism and nutrition disorders: hypoglycemia

Nervous System disorders: dizziness

Respiratory, thoracic and mediastinal disorders: bronchospasm

Skin and Subcutaneous Tissue disorders: urticaria

Vascular disorders: flushing, phlebitis, wound hemorrhage, spontaneous hematoma
      

Alanine Aminotransferase (ALT) Elevations

Among patients with normal baseline ALT levels, more DALVANCE- than comparator-treated patients had post-baseline ALT elevations greater than 3 times the upper limit of normal (ULN), 12 (0.8%) vs. 2 (0.2%), respectively including three subjects with post-baseline ALT values greater than 10 times ULN. Eight of 12 patients treated with DALVANCE and one comparator patient had underlying conditions which could affect liver enzymes, including chronic viral hepatitis and a history of alcohol abuse. In addition, one DALVANCE-treated subject in a Phase 1 trial had post-baseline ALT elevations greater than 20 times ULN. ALT elevations were reversible in all subjects. No comparator-treated subject with normal baseline transaminases had post-baseline ALT elevation greater than 10 times ULN.

Specific information is not available on the treatment of overdose with DALVANCE, as dose-limiting toxicity has not been observed in clinical studies. In Phase 1 studies, healthy volunteers have been administered single doses of up to 1500 mg, and cumulative doses of up to 4500 mg over a period of up to 8 weeks, with no signs of toxicity nor laboratory results of clinical concern.

Treatment of overdose with DALVANCE should consist of observation and general supportive measures. Although no information is available specifically regarding the use of hemodialysis to treat overdose, in a Phase 1 study in patients with renal impairment less than 6% of the recommended dalbavancin dose was removed [see Clinical Pharmacology (12.3)].

DALVANCE (dalbavancin) for injection is a lipoglycopeptide synthesized from a fermentation product of Nonomuraea species.

Dalbavancin is a mixture of five closely related active homologs (A0, A1, B0, B1, and B2); the component B0 is the major component of dalbavancin. The homologues share the same core structure and differ in the fatty acid side chain of the N-acylaminoglucuronic acid moiety (R1) structure and/or the presence of an additional methyl group (R2) on the terminal amino group (shown in the figure and table below).

Figure 1. Dalbavancin Structural Formula

*Anhydrous free base

The B0 INN chemical name is: 5,31-dichloro-38-de(methoxycarbonyl)-7-demethyl-19-deoxy-56-O-[2-deoxy-2-[(10-methylundecanoyl)amino]-β-D-glucopyranuronosyl]-38-[[3-(dimethylamino)propyl] carbamoyl]-42-O-α-D-mannopyranosyl-15-N-methyl(ristomycin A aglycone) hydrochloride.

DALVANCE is supplied in clear glass vials as a sterile, lyophilized, preservative-free, white to off-white to pale yellow solid. Each vial contains dalbavancin HCl equivalent to 500 mg of anhydrous dalbavancin as the free base, plus lactose monohydrate (129 mg) and mannitol (129 mg) as excipients. Sodium hydroxide or hydrochloric acid may be added to adjust the pH at the time of manufacture. The powder is to be reconstituted and further diluted for IV infusion [see Dosage and Administration (2.3) and How Supplied/Storage and Handling (16)].

1. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antibiotic Susceptibility Tests for Bacteria That Grow Aerobically; Approved StandardNinth Edition. CLSI document M07-A9. Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2012.
2. CLSI. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Third Informational Supplement.  CLSI document M100-S23 Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2013.