treated with DALVANCE in Phase 2 and 3 clinical trials, 313 patients (17.7%) were 65 years of age or older. The efficacy and tolerability of DALVANCE were similar to comparator regardless of age. The pharmacokinetics of dalbavancin were not significantly altered with age; therefore, no dosage adjustment is necessary based on age alone.
DALVANCE is substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in this age group.
8.6 Renal ImpairmentIn patients with renal impairment whose known creatinine clearance is less than 30 mL/min and who are not receiving regularly scheduled hemodialysis, the recommended two-dose regimen for DALVANCE is 750 mg followed one week later by 375 mg. No dosage adjustment is recommended for patients receiving regularly scheduled hemodialysis, and DALVANCE can be administered without regard to the timing of hemodialysis [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].
8.7 Hepatic ImpairmentNo dosage adjustment of DALVANCE is recommended for patients with mild hepatic impairment (Child-Pugh Class A). Caution should be exercised when prescribing dalbavancin to patients with moderate or severe hepatic impairment (Child-Pugh Class B or C) as no data are available to determine the appropriate dosing in these patients [see Clinical Pharmacology (12.3)].
10 OVERDOSAGE
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)].
11 DESCRIPTION
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
Table 2. Substitution Patterns for Dalbavancin API Homologs Dalbavancin
R1
R2
Molecular Formula
Molecular Weight*
A0
CH(CH3)2
H
C87H98N10O28Cl2 · 1.6 HCl
1802.7
A1
CH2CH2CH3
H
C87H98N10O28Cl2 · 1.6 HCl
1802.7
B0
CH2CH(CH3)2
H
C88H100N10O28Cl2 · 1.6 HCl
1816.7
B1
CH2CH2CH2CH3
H
C88H100N10O28Cl2 · 1.6 HCl
1816.7
B2
CH2CH(CH |
