Dosing and uses of Dalvance (dalbavancin)
Adult dosage forms and strengths
lyophilized powder for reconstitution
- 500mg/vial (20mg/mL after reconstitution)
Skin & Skin Structure Infections
Indicated for acute bacterial skin and skin structure infections (ABSSSI) caused by gram-positive bacteria
1-dose regimen of 1500 mg IV, or
2-dose regimen of 1000 mg IV followed 1 week later by 500 mg IV
Infuse IV over 30 minutes
Susceptible isolates of Gram-positive microorganisms
- Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant Staphylococcus aureus [MRSA])
- Streptococcus pyogenes
- Streptococcus agalactiae
- Streptococcus anginosus group (including S anginosus, S intermedius, S constellatus)
Dosage modifications
Renal impairment
- CrCl <30 mL/min
- 1-dose regimen: Decrease dose to 1125 mg IV
- 2-dose regimen: Decrease dose to 750 mg IV followed 1 week later by 375 mg IV
- If receiving regularly scheduled hemodialysis: No dosage adjustment required
Hepatic impairment
- Mild (Child-Pugh A): No dosage adjustment required
- Moderate or severe (Child-Pugh B and C): Cautions, no data are available
Pediatric dosage forms and strengths
Safety and efficacy not established
Osteomyelitis (Orphan)
Orphan designation for treatment of acute osteomyelitis in children aged ≤16 yr
Sponsor
- Durata Therapeutics International B.V.; Spaces Zuidas II, Kantoor 4.03; 1083HN, Amsterdam; Netherlands
Dalvance (dalbavancin) adverse (side) effects
2-10%
Nausea (5.5%)
Headache (4.7%)
Diarrhea (4.4%)
Vomiting (2.8%)
Rash (2.7%)
Pruritus (2.1%)
<2%
Blood and lymphatic system disorders: Anemia, hemorrhagic anemia, leukopenia, 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, INR 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
Elevated ALT, >3x ULN (0.8%)
Warnings
Contraindications
Hypersensitivity
Cautions
Serious hypersensitivity (anaphylactic) and skin reactions reported with glycopeptide antibacterial agents, including dalbavancin
Rapid IV infusion of glycopeptide antibacterial agents can cause reactions, including upper body flushing, urticaria, pruritus, and rash
ALT elevations >3x ULN reported
Clostridium difficile-associated diarrhea (CDAD) reported with nearly all systemic antibacterial agents, including dalbavancin; evaluate if diarrhea occurs
Prescribing antibiotics in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit and increases the risk of the development of drug-resistant bacteria
Pregnancy and lactation
Pregnancy category: C
No evidence of embryo or fetal toxicity was found in the rat or rabbit at a dose of 15 mg/kg/day (1.2 and 0.7 times the human dose on an exposure basis, respectively)
Delayed fetal maturation was observed in the rat at a dose of 45 mg/kg/day (3.5 times the human dose on an exposure basis)
Lactation: Unknown if distributed in human breast milk
Excreted in milk of lactating rats
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Dalvance (dalbavancin)
Mechanism of action
Lipoglycopeptide antibiotic; interferes with cell wall synthesis by binding to D-alanyl-D-alanine terminus of the stem pentapeptide in nascent cell wall peptidoglycan, thus preventing cross-linking
Bactericidal in vitro against Staphylococcus aureus and Streptococcus pyogenes at concentrations observed in humans at recommended doses
Absorption
Single 1000 mg dose
- Peak plasma concentration: 4287 mg/L
- AUC 0-24: 3185 mg•hr/L
- AUC 0-Day7: 11,160 mg•hr/L
- AUC 0-inf: 23,443 mg•hr/L
Single 1500 mg dose
- Peak plasma concentration: 423 mg/L
- AUC 0-24: 4837 mg•hr/L
Distribution
Protein bound, reversible: 93%, primarily albumin
Metabolism
Not a substrate, inhibitor, or inducer of CYP450 isoenzymes
Minor metabolite (hydroxy-dalbavancin) observed in urine
Elimination
Half-life: 346 hr (single 1000 mg dose)
Clearance: 0.513 L/hr (single 1000 mg dose)
Excretion: 33% unchanged in urine; 12% metabolite in urine; 20% in feces
Administration
IV Compatabilities
Dextrose 5%
IV Incompatabilities
Saline-based solutions (precipitation occurs)
Compatibility of reconstituted dalbavancin with IV medications, additives, or substances other than 5% dextrose has not been established
IV Preparation
Reconstitution
- Reconstitute under aseptic conditions, using 25 mL of sterile water for injection for each 500-mg vial
- To avoid foaming, alternate between gentle swirling and inversion of the vial until its contents are completely dissolved
- Do NOT shake
- Reconstituted vial contains 20 mg/mL
- Reconstituted solution should appear clear and colorless to yellow
Dilution
- Aseptically transfer the required dose of reconstituted solution from the vial(s) to IV bag or bottle containing D5W
- Final concentration of diluted solution must be between 1 mg/mL and 5 mg/mL
- Discard any unused portion of the reconstituted vials
IV Administration
Visually inspect for particulate matter before infusion
If common IV line is being used to administer other drugs in addition to dalbavancin, the line should be flushed before and after each dose
Infuse IV over 30 minutes
Infusion-related reactions associated with rapid IV infusion
Storage
Reconstituted vials or diluted solution
- Store either refrigerated at 2-8°C (36-46 °F), or at controlled room temperature 20-25°C (68-77°F)
- Do not freeze
- Total time from reconstitution to dilution to administration should not exceed 48 hr
