3)2
CH3
C89H102N10O28Cl2 · 1.6 HCl
1830.7
*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)].
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of ActionDalbavancin is an antibacterial drug [see Clinical Pharmacology (12.4)]
12.2 PharmacodynamicsThe antibacterial activity of dalbavancin appears to best correlate with the ratio of area under the concentration-time curve to minimal inhibitory concentration (AUC/MIC) for Staphylococcus aureus based on animal models of infection. An exposure-response analysis of a single study in patients with complicated skin and skin structure infections supports the two-dose regimen [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3)].
Cardiac Electrophysiology: In a randomized, positive- and placebo-controlled, thorough QT/QTc study, 200 healthy subjects received dalbavancin 1000 mg IV, dalbavancin 1500 mg IV, oral moxifloxacin 400 mg, or placebo. Neither dalbavancin 1000 mg nor dalbavancin 1500 mg (supratherapeutic dose) had any clinically relevant adverse effect on cardiac repolarization.
12.3 PharmacokineticsDalbavancin pharmacokinetic parameters have been characterized in healthy subjects, patients, and specific populations. Pharmacokinetic parameters following administration of a single intravenous 1000 mg dose were as shown in Table 3. The pharmacokinetics of dalbavancin can be described using a three-compartment model.
Table 3. Dalbavancin Pharmacokinetic Parameters in Healthy Subjects Parameter
Single 1000 mg Dose
Cmax (mg/L)
287 (13.9)1
AUC0-24 (mg•h/L)
3185 (12.8)1
AUC0-Day7 (mg•h/L)
11160 (41.1)2
AUC0-inf (mg•h/L)
23443 (40.9)2
Terminal t½ (h)
346 (16.5)2,3
CL (L/h)
0.0513 (46.8)2
All values are presented as mean (% coefficient of variation)
1 Data from 50 healthy subjects.
2 Data from 12 healthy subjects.
3 Based upon population pharmacokinetic analyses of data from patients, the effective half-life is approximately 8.5 days (204 hours).
In healthy subjects, dalbavancin AUC0-24h and Cmax both increased proportionally to dose following single IV dalbavancin doses ranging from 140 mg to 1500 mg, indicating linear pharmacokinetics.
The mean plasma concentration-time profile for dalbavancin at the recommended two-dose regimen of 1000 mg followed one week later by 500 mg is shown in Figure 2.
Figure 2. Mean (± standard deviation) dalbavancin plasma concentrations versus time in healthy
