tic Impairment: The pharmacokinetics of dalbavancin were eva luated in 17 subjects with mild, moderate, or severe hepatic impairment (Child-Pugh class A, B or C) and compared to those in nine matched healthy subjects with normal hepatic function. The mean AUC0-336 hrs was unchanged in subjects with mild hepatic impairment compared to subjects with normal hepatic function; however, the mean AUC0-336 hrs decreased 28% and 31% in subjects with moderate and severe hepatic impairment respectively, compared to subjects with normal hepatic function. The clinical significance of the decreased AUC0-336 hrs in subjects with moderate and severe hepatic function is unknown.
No dosage adjustment is recommended for patients with mild hepatic impairment. Caution should be exercised when prescribing dalbavancin to patients with moderate or severe hepatic impairment as no data are available to determine the appropriate dosing.
Gender: Clinically significant gender-related differences in dalbavancin pharmacokinetics have not been observed either in healthy subjects or in patients with infections. No dosage adjustment is recommended based on gender.
Geriatric Patients: Clinically significant age-related differences in dalbavancin pharmacokinetics have not been observed in patients with infections. No dosage adjustment is recommended based solely on age.
Pediatric Patients: The pharmacokinetics of dalbavancin in pediatric populations <12 years of age have not been established.
Drug Interactions
Nonclinical studies demonstrated that dalbavancin is not a substrate, inhibitor, or inducer of CYP450 isoenzymes. In a population pharmacokinetic analysis, dalbavancin pharmacokinetics were not affected by co‑administration with known CYP450 substrates, inducers or inhibitors, nor by individual medications including acetaminophen, aztreonam, fentanyl, metronidazole, furosemide, proton pump inhibitors (omeprazole, esomeprazole, pantoprazole, lansoprazole), midazolam, and simvastatin.
12.4 MicrobiologyMechanism of Action
Dalbavancin, a semisynthetic lipoglycopeptide, 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.
Mechanism of Resistance
The development of bacterial isolates resistant to dalbavancin has not been observed, either in vitro, in studies using serial passage, or in animal infection experiments.
Interaction with Other Antimicrobials
When tested in vitro, dalbavancin demonstrated synergistic interactions with oxacillin and did not demonstrate antagonistic or synergistic interactions with any of the following antibacterial agents of various classes: gentamicin, vancomycin, levofloxacin, clindamycin, quinupristin/dalfopristin, linezolid, aztreonam, rifampin or daptomycin. The clinical significance of these in vitro findings is unknown.
Dalbavancin has been shown to be active against the following microorganisms, both in vitro and in clinical infections [see Indications and Usage (1)].
Gram-positive bacteria
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