dalbavancin (Rx)

1-10%

Adults

• Nausea (5.5%)
• Headache (4.7%)
• Diarrhea (4.4%)
• Vomiting (2.8%)
• Rash (2.7%)
• Pruritus (2.1%)

<2% (adults)

• 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, blood lactate dehydrogenase increased, gamma-glutamyl transferase increased
• Metabolism and nutrition disorders: Hypoglycemia
• Nervous system disorders: Dizziness
• Respiratory, thoracic and mediastinal disorders: Bronchospasm
• Skin and subcutaneous tissue disorders: Rash, pruritus, urticaria
• Vascular disorders: Flushing, phlebitis, wound hemorrhage, spontaneous hematoma

Pediatrics

• Pyrexia (1.2%)

<1%

Adults

• Elevated ALT, >3x ULN (0.8%)

Pediatrics

• Gastrointestinal disorders: Diarrhea
• Nervous system disorders: Dizziness
• Skin and subcutaneous tissue disorders: Pruritus

Postmarketing Reports

Back pain as an infusion-related reaction

Contraindications

Hypersensitivity

Cautions

Administer via intravenous infusion, using a total infusion time of 30 minutes to minimize risk of infusion-related reaction; rapid IV infusion of glycopeptide antibacterial agents can cause reactions, including upper body flushing, urticaria, pruritus, back pain, and rash; stopping or slowing infusion may result in cessation of these reactions

ALT elevations >3x ULN reported

Prescribing antibiotics in the absence of a proven or strongly suspected bacterial infection, or a prophylactic indication is unlikely to provide benefit and increases the risk of the development of drug-resistant bacteria

Clostridioides difficile-associated diarrhea (CDAD)

• CDAD reported with severity ranging from mild diarrhea to fatal colitis; treatment with antibacterial agents can alter normal flora of the colon, and may permit overgrowth of C. difficile
• C. difficile produces toxins A and B which contribute to development of CDAD; hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antibacterial therapy and may require colectomy
• CDAD must be considered in all patients who present with diarrhea following antibacterial use; careful medical history necessary because CDAD has been reported to occur more than 2 months after administration of antibacterial agents
• If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile should be discontinued, if possible appropriate measures such as fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated

Hypersensitivity reactions

• Serious hypersensitivity (anaphylactic) and skin reactions reported with glycopeptide antibacterial agents, including dalbavancin
• If an allergic reaction occurs, discontinue treatment and institute appropriate therapy for the allergic reaction; before using product, inquire carefully about previous hypersensitivity reactions to other antimicrobials#glycopeptides
• Due to the possibility of cross-sensitivity, carefully monitor for signs of hypersensitivity during treatment in patients with a history of glycopeptide allergy

Pregnancy

There are no adequate and well-controlled studies with use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse developmental outcomes

No treatment-related malformations or embryo-fetal toxicity were observed in pregnant rats or rabbits at clinically relevant exposures of dalbavancin

Treatment of pregnant rats with dalbavancin at 3.5 times the human dose on an exposure basis during early embryonic development and from implantation to the end of lactation resulted in delayed fetal maturation and increased fetal loss, respectively

Lactation

There are no data on presence of dalbavancin or its metabolite in human milk, effects on breastfed child, or on milk production

Dalbavancin is excreted in the milk of lactating rats; when a drug is present in animal milk, it is likely that the drug will be present in human milk

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breast-fed child from the drug or from the underlying maternal condition

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.

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

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 required dose of reconstituted solution from vial(s) to IV bag or bottle containing D5W
• Final concentration of diluted solution must be between 1-5 mg/mL
• Discard any unused portion of 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, flush line before and after each dose

Infuse IV over 30 minutes

Infusion-related reactions associated with rapid IV infusion

Storage

Unopened vials: Store at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF)

Reconstituted vials or diluted solution

• May refrigerate at 2-8°C (36-46°F) or store 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