Usage
Dalbavancin is prescribed for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) in adults and pediatric patients aged 3 months and older. It is effective against susceptible Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus anginosus group (including S. anginosus, S. intermedius, and S. constellatus).
It is classified as a lipoglycopeptide antibiotic.
Dalbavancin’s mechanism of action involves inhibiting bacterial cell wall synthesis by binding to the D-alanyl-D-alanyl residue on growing peptidoglycan chains. This binding prevents transpeptidation and peptidoglycan elongation, ultimately leading to bacterial cell death. Its lipophilic properties allow it to anchor in the bacterial membrane, enhancing its activity.
Alternate Names
Dalbavancin is also marketed under the brand name Dalvance and Xydalba.
How It Works
Pharmacodynamics: Dalbavancin exhibits bactericidal activity by disrupting cell wall biosynthesis in susceptible Gram-positive bacteria. It binds to the terminal D-alanyl-D-alanyl residues of peptidoglycan precursors, preventing cross-linking and subsequent cell wall formation. It also dimerizes and anchors in the bacterial membrane, enhancing its binding and stability.
Pharmacokinetics:
- Absorption: Dalbavancin is administered intravenously, achieving rapid distribution into various tissues, including bone and joint tissues.
- Metabolism: Dalbavancin is not extensively metabolized.
- Elimination: Primarily eliminated through renal excretion, with a small portion eliminated in the feces. It has a long half-life, allowing for once-weekly dosing.
Mode of Action: Dalbavancin inhibits transpeptidation and transglycosylation, essential steps in bacterial cell wall synthesis. It binds to the D-Ala-D-Ala terminus of the peptidoglycan precursor, preventing the formation of cross-links between peptidoglycan chains.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Dalbavancin’s primary mechanism is the targeted binding to the D-Ala-D-Ala terminus of peptidoglycan precursors. It does not have significant interactions with CYP450 enzymes or neurotransmitter systems.
Elimination Pathways: Dalbavancin is predominantly excreted unchanged in the urine.
Dosage
Standard Dosage
Adults:
- Single-Dose Regimen: 1500 mg IV infused over 30 minutes.
- Two-Dose Regimen: 1000 mg IV infused over 30 minutes followed by 500 mg IV infused over 30 minutes one week later.
Children (3 months and older):
- Children (6 years to <18 years): Single dose of 18 mg/kg (maximum 1500 mg) IV infused over 30 minutes.
- Infants and Children (3 months to <6 years): Single dose of 22.5 mg/kg (maximum 1500 mg) IV infused over 30 minutes.
Special Cases:
- Elderly Patients: No dosage adjustment is generally necessary.
- Patients with Renal Impairment (CrCl < 30 mL/min not receiving regular hemodialysis):
- Single-Dose: 1000 mg IV
- Two-Dose: 750 mg IV followed by 375 mg IV one week later.
- Patients with Hepatic Dysfunction: Caution is advised in patients with moderate or severe hepatic impairment; no specific dosage adjustments are available.
- Patients with Comorbid Conditions: Individualized dosing may be necessary depending on specific comorbid conditions.
Clinical Use Cases
Dalbavancin is specifically indicated for ABSSSIs and is not typically used in clinical scenarios like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations requiring immediate intervention. Its long half-life and targeted activity make it suitable for outpatient treatment of ABSSSIs.
Dosage Adjustments
Dosage adjustments are primarily required for patients with severe renal impairment (CrCl < 30 mL/min and not receiving hemodialysis). No adjustments are needed for patients receiving regular hemodialysis.
Side Effects
Common Side Effects
Nausea, headache, diarrhea, rash, itching, and vomiting.
Rare but Serious Side Effects
- Hypersensitivity reactions (including anaphylaxis)
- Clostridium difficile-associated diarrhea (CDAD)
- Liver enzyme elevations
- Red man syndrome (with rapid infusion)
Long-Term Effects
Limited data are available on long-term effects.
Adverse Drug Reactions (ADR)
Anaphylaxis, severe skin reactions, and CDAD.
Contraindications
Known hypersensitivity to dalbavancin.
Drug Interactions
Limited potential for drug interactions due to minimal CYP450 metabolism. However, concurrent use with certain drugs (e.g., hormonal contraceptives, certain transporter inhibitors) warrants caution.
Pregnancy and Breastfeeding
Pregnancy Safety Category: C (consult a healthcare provider)
Fetal risks are not well established, but animal studies showed potential adverse effects. It is unknown if dalbavancin is excreted in human milk; caution is advised.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial cell wall synthesis.
- Side Effects: Nausea, headache, diarrhea, rash, itching, vomiting. Rare: hypersensitivity reactions, C. difficile infection, liver enzyme elevations.
- Contraindications: Hypersensitivity to dalbavancin.
- Drug Interactions: Minimal potential for drug-drug interactions. Monitor for potential interactions with hormonal contraceptives and certain transporter inhibitors.
- Pregnancy & Breastfeeding: Category C; caution advised.
- Dosage: Adults: 1500 mg single dose or 1000 mg followed by 500 mg after one week. Pediatric: Weight-based dosing. Adjustments needed for severe renal impairment.
- Monitoring Parameters: Monitor for signs of hypersensitivity reactions, C. difficile infection, and liver enzyme elevations.
Popular Combinations
Dalbavancin is often used as monotherapy for ABSSSIs. Combination therapy may be considered for polymicrobial infections or in cases of suspected or documented resistance.
Precautions
Assess for hypersensitivity to dalbavancin or other glycopeptides before administration. Exercise caution in patients with hepatic impairment. Infuse over 30 minutes to minimize the risk of red man syndrome. Monitor for signs of allergic reactions, C. difficile infection, and liver function abnormalities. Patient counseling regarding contraception is recommended.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Dalbavancin?
A: Adults: 1500 mg single dose or 1000 mg followed by 500 mg after one week. Children: Weight-based dosing (18 mg/kg for 6 to <18 years, 22.5 mg/kg for 3 months to <6 years; maximum 1500 mg). Adjust for severe renal impairment.
Q2: What is the mechanism of action of Dalbavancin?
A: Dalbavancin inhibits bacterial cell wall synthesis by binding to the D-alanyl-D-alanyl terminus of peptidoglycan precursors, preventing cross-linking and cell wall formation.
Q3: What are the common side effects of Dalbavancin?
A: Nausea, headache, diarrhea, rash, itching, and vomiting.
Q4: What are the serious side effects of Dalbavancin?
A: Hypersensitivity reactions (including anaphylaxis), Clostridium difficile-associated diarrhea, and liver enzyme elevations. Red man syndrome can occur with rapid infusion.
Q5: Is Dalbavancin safe during pregnancy?
A: Dalbavancin is a Pregnancy Category C drug. Use only if the potential benefit justifies the potential risk to the fetus.
Q6: Can Dalbavancin be used in patients with renal impairment?
A: Dosage adjustments are required for patients with severe renal impairment (CrCl < 30 mL/min not receiving regular hemodialysis). No adjustments are necessary for those receiving regular hemodialysis.
Q7: How is Dalbavancin administered?
A: Dalbavancin is administered intravenously over 30 minutes.
Q8: What infections is Dalbavancin used to treat?
A: Dalbavancin is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSIs).
Q9: Does Dalbavancin interact with other medications?
A: Dalbavancin has a low potential for drug interactions but may reduce the effectiveness of hormonal contraceptives. Caution is also advised with concomitant use of certain transporter inhibitors.
Q10: How long does Dalbavancin stay in the body?
A: Dalbavancin has a long half-life, allowing for once-weekly dosing. Therapeutic levels can persist for several days after administration.
