Identification

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Name
Dalbavancin
Accession Number
DB06219
Type
Small Molecule
Groups
Approved, Investigational
Description

Dalbavancin is a second-generation lipoglycopeptide antibiotic that was designed to improve on the natural glycopeptides currently available, such as vancomycin and teicoplanin 1,2. Modifications from these older glycoprotein classes facilitated a similar mechanism of action for dalbavancin but with increased activity and once-weekly dosing Label,4,1,2. Its use is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by the following gram-positive microorganisms: Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant strains), S. pyogenes, S. agalactiae, S. dysgalactiae, the S. anginosus group (including S. anginosus, S. intermedius, and S. constellatus), and Enterococcus faecalis (vancomycin susceptible strains) Label,4. Dalbavancin acts by interfering with bacterial cell wall synthesis by binding to the D-alanyl-D-alanine terminus of nascent cell wall peptidoglycan and preventing cross-linking Label,4,1,2.

Synonyms
  • Dalbavancin
  • Dalbavancina
External IDs
A-A-1 / B 397 / B397 / BI 387 / BI-387 / MDL 64,397 / MDL-64397 / VER-001 / VER001
Product Ingredients
IngredientUNIICASInChI Key
Dalbavancin hydrochloride33WDQ7T81ENot AvailableNot applicable
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DalvanceInjection, powder, for solution500 mg/25mLIntravenousDurata Therapeutics Inc.2014-05-23Not applicableUs
XydalbaPowder, for solutionIntravenousCipher Pharmaceuticals Inc.Not applicableNot applicableCanada
XydalbaInjection, powder, for solution500 mgIntravenousAllergan2015-02-19Not applicableEu
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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International/Other Brands
Zeven (Pfizer)
Categories
UNII
808UI9MS5K
CAS number
171500-79-1

Pharmacology

Indication

Dalbavancin for injection is indicated for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSI), caused by susceptible isolates of the following gram-positive microorganisms: Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant strains), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus anginosus group (including Streptococcus anginosus, Streptococcus intermedius, Streptococcus constellatus) and Enterococcus faecalis (vancomycin susceptible strains) Label,4.

Dalbavancin is not active against gram-negative bacteria; therefore, combination therapy may be clinically indicated if the ABSSSI is polymicrobial and includes a suspected or documented gram-negative pathogen 4.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of dalbavancin and other antibacterial drugs, dalbavancin should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria Label,4. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy Label,4. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy Label,4.

Associated Conditions
Pharmacodynamics

The 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 Label,4. An exposure-response analysis of a single study in patients with complicated skin and skin structure infections supports the two-dose regimen for which dalbavancin injection is administered Label,4.

Subsequently, the recommended dosage regimen of dalbavancin in patients with normal renal function is 1500 mg, administered either as a single dose, or 1000 mg followed one week later by 500 mg [FDA Label, F2356. Dalbavancin should be administered over 30 minutes by intravenous infusion Label,4.

Furthermore, inn a randomized, positive- and placebo-controlled, thorough QT/QTc study, 200 healthy subjects received either dalbavancin 1000 mg intravenous (IV), dalbavancin 1500 mg IV, oral moxifloxacin 400 mg, or placebo. Neither dalbavancin 1000 mg nor dalbavancin 1500 mg had any clinically relevant adverse effect on cardiac repolarization Label,4.

Mechanism of action

Dalbavancin has a spectrum and mechanism of action similar to vancomycin, a naturally formed glycopeptide antimicrobial 2. The bactericidal action of dalbavancin results primarily from inhibition of cell-wall biosynthesis Label,4,1,2,3. Specifically, dalbavancin prevents incorporation of N-acetylmuramic acid (NAM)- and N-acetylglucosamine (NAG)-peptide subunits from being incorporated into the peptidoglycan matrix; which forms the major structural component of Gram-positive cell walls 1,2. The large hydrophilic molecule is able to form hydrogen bond interactions with the terminal D-alanyl-D-alanine moieties of the NAM/NAG-peptides, which is normally a five-point interaction Label,1,2. Binding of dalbavancin to the D-Ala-D-Ala prevents the incorporation of the NAM/NAG-peptide subunits into the peptidoglycan matrix Label,1,2. In addition, dalbavancin alters bacterial-cell-membrane permeability and RNA synthesis.

TargetActionsOrganism
AD-Ala-D-Ala moiety of NAM/NAG peptide subunits of peptidoglycan
binder
Gram-positive Bacteria
Additional Data Available
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Contraindications

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Blackbox Warnings

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Absorption

In healthy subjects, dalbavancin AUC0-24h and Cmax both increased proportionally to dose following single intravenous (IV) dalbavancin doses ranging from 140 mg to 1500 mg, indicating linear pharmacokinetics Label,4.

No apparent accumulation of dalbavancin was observed following multiple IV infusions administered once weekly for up to eight weeks, with 1000 mg on Day 1 followed by up to seven weekly 500 mg doses, in healthy adults with normal renal function Label,4.

Volume of distribution

Clearance and volume of distribution at steady state are comparable between healthy subjects and patients with infections 5. The volume of distribution at steady state was similar to the volume of extracellular fluid 5.

Protein binding

Dalbavancin is reversibly bound to human plasma proteins, primarily to albumin Label,4. The plasma protein binding of dalbavancin is 93% and is not altered as a function of drug concentration, renal insufficiency, or hepatic insufficiency Label,4.

Metabolism

Dalbavancin is not a substrate, inhibitor, or inducer of CYP450 isoenzymes Label,4. Subsequently, metabolites have not been observed in significant amounts in human plasma Label,4. The metabolites hydroxy-dalbavancin and mannosyl aglycone have been detected in urine (< 25% of administered dose) Label,4. The metabolic pathways responsible for producing these metabolites have not been identified; however, due to the relatively minor contribution of metabolism to the overall elimination of dalbavancin, drug-drug interactions via inhibition or induction of metabolism of dalbavancin are not anticipated Label,4. Hydroxy-dalbavancin and mannosyl aglycone show significantly less antibacterial activity compared to dalbavancin Label,4.

Route of elimination

Following administration of a single 1000 mg dose in healthy subjects, an average of 33% of the administered dalbavancin dose was excreted in urine as unchanged dalbavancin and approximately 12% of the administered dose was excreted in urine as the metabolite hydroxy-dalbavancin through 42 days post-dose. Approximately 20% of the administered dose was excreted in feces through 70 days post-dose Label,4.

Half life

Terminal half life is 346 hours Label,4.

Clearance

0.0513 L/h Label,4.

Toxicity

Treatment with antibacterial agents can alter the normal flora of the colon leading to growth of C. difficile and commonly occurs in the development of C. difficile-associated diarrhea Label,4. Other common side effects include nausea, vomiting, diarrhea, headache, rash, and pruritis Label,4. Side effects that occurred in less than 2% of patients during clinical trials include blood and lymphatic system disorders, gastrointestinal disorders, hepatotoxicity, anaphylactoid reactions, hepatic enzyme elevation, hypoglycaemia, dizziness, bronchospasm, urticaria, and vascular disorders Label,4. There have been no adequate or well-controlled studies to conclude that use of dalbavancin is safe during pregnancy or breastfeeding Label,4.

Affected organisms
  • Gram-positive Bacteria
  • Streptococcus pyogenes
  • Streptococcus agalactiae
  • Staphylococcus aureus
  • Enterococcus faecalis
  • Streptococcus anginosus
  • Staphylococcus intermedius
  • Streptococcus constellatus
  • Streptococcus dysgalactiae
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Dalbavancin is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Dalbavancin is combined with (S)-Warfarin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Dalbavancin is combined with 4-hydroxycoumarin.
AcenocoumarolThe risk or severity of bleeding can be increased when Dalbavancin is combined with Acenocoumarol.
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Dalbavancin.
ClorindioneThe risk or severity of bleeding can be increased when Dalbavancin is combined with Clorindione.
CoumarinThe risk or severity of bleeding can be increased when Dalbavancin is combined with Coumarin.
DicoumarolThe risk or severity of bleeding can be increased when Dalbavancin is combined with Dicoumarol.
DiphenadioneThe risk or severity of bleeding can be increased when Dalbavancin is combined with Diphenadione.
Ethyl biscoumacetateThe risk or severity of bleeding can be increased when Dalbavancin is combined with Ethyl biscoumacetate.
Additional Data Available
  • Extended Description
    Extended Description

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  • Severity
    Severity

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  • Evidence Level
    Evidence Level

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  • Action
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Food Interactions
Not Available

References

General References
  1. Bailey J, Summers KM: Dalbavancin: a new lipoglycopeptide antibiotic. Am J Health Syst Pharm. 2008 Apr 1;65(7):599-610. doi: 10.2146/ajhp070255. [PubMed:18359966]
  2. Bennett JW, Lewis JS, Ellis MW: Dalbavancin in the treatment of complicated skin and soft-tissue infections: a review. Ther Clin Risk Manag. 2008 Feb;4(1):31-40. [PubMed:18728718]
  3. Leuthner KD, Yuen A, Mao Y, Rahbar A: Dalbavancin (BI-387) for the treatment of complicated skin and skin structure infection. Expert Rev Anti Infect Ther. 2015 Feb;13(2):149-59. doi: 10.1586/14787210.2015.995633. [PubMed:25578881]
  4. Dalbavacin Health Canada Product Monograph [File]
  5. Dalbavancin EMA Label [File]
External Links
KEGG Drug
D03640
PubChem Compound
23724878
PubChem Substance
310264863
ChemSpider
30791917
ChEBI
82721
ChEMBL
CHEMBL3301669
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Dalbavancin
ATC Codes
J01XA04 — Dalbavancin
FDA label
Download (1.96 MB)
MSDS
Download (103 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableBacterial Infections2
1RecruitingBasic ScienceBacterial Infections1
1TerminatedBasic ScienceBacterial Infections1
2CompletedTreatmentOsteomyelitis1
2TerminatedTreatmentBacteremia / Endocarditis / Infective Endocarditis, Bacteremia1
2TerminatedTreatmentOsteomyelitis1
2Unknown StatusTreatmentBacteremia1
3CompletedTreatmentAbscesses / Cellulitis / Surgical Site Infections / Wound Infections3
3RecruitingTreatmentBacterial Infections / Methicillin-Resistant Staphylococcus Aureus (MRSA) / Staphylococcal Skin Infections1
3WithdrawnTreatmentCommunity Acquired Pneumonia (CAP)1
3WithdrawnTreatmentOsteomyelitis1
4CompletedBasic ScienceInfectious Peritonitis1
4CompletedTreatmentAcute acute bacterial skin and skin structure infections / Bacterial Infections1
4CompletedTreatmentAcute acute bacterial skin and skin structure infections1
4Not Yet RecruitingTreatmentInfections, Gram-Positive Bacterial / Soft Tissues Infections1
4RecruitingTreatmentBone Infection / Joint Infections / Osteomyelitis / Prosthetic Joint Infection / Septic Arthritis1
4RecruitingTreatmentSkin-structure infections1
Not AvailableNot Yet RecruitingNot AvailableBacterial Infections1
Not AvailableRecruitingNot AvailableBacterial Infections1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, for solutionIntravenous500 mg/25mL
Injection, powder, for solutionIntravenous500 mg
Powder, for solutionIntravenous
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6900175No2005-05-312023-12-25Us
US8143212No2012-03-272023-11-14Us
US7119061No2006-10-102023-11-14Us
US7115564No2006-10-032023-11-14Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
Not Available
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8291
Blood Brain Barrier-0.9949
Caco-2 permeable-0.6459
P-glycoprotein substrateSubstrate0.9269
P-glycoprotein inhibitor INon-inhibitor0.6135
P-glycoprotein inhibitor IINon-inhibitor0.566
Renal organic cation transporterNon-inhibitor0.8977
CYP450 2C9 substrateNon-substrate0.8413
CYP450 2D6 substrateNon-substrate0.842
CYP450 3A4 substrateSubstrate0.6971
CYP450 1A2 substrateNon-inhibitor0.9024
CYP450 2C9 inhibitorNon-inhibitor0.7822
CYP450 2D6 inhibitorNon-inhibitor0.794
CYP450 2C19 inhibitorNon-inhibitor0.8182
CYP450 3A4 inhibitorNon-inhibitor0.769
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8728
Ames testNon AMES toxic0.6111
CarcinogenicityNon-carcinogens0.8555
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7256 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9445
hERG inhibition (predictor II)Inhibitor0.7467
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

1. D-Ala-D-Ala moiety of NAM/NAG peptide subunits of peptidoglycan
Kind
Group
Organism
Gram-positive Bacteria
Pharmacological action
Yes
Actions
Binder
References
  1. Bailey J, Summers KM: Dalbavancin: a new lipoglycopeptide antibiotic. Am J Health Syst Pharm. 2008 Apr 1;65(7):599-610. doi: 10.2146/ajhp070255. [PubMed:18359966]
  2. Bennett JW, Lewis JS, Ellis MW: Dalbavancin in the treatment of complicated skin and soft-tissue infections: a review. Ther Clin Risk Manag. 2008 Feb;4(1):31-40. [PubMed:18728718]
  3. Leuthner KD, Yuen A, Mao Y, Rahbar A: Dalbavancin (BI-387) for the treatment of complicated skin and skin structure infection. Expert Rev Anti Infect Ther. 2015 Feb;13(2):149-59. doi: 10.1586/14787210.2015.995633. [PubMed:25578881]
  4. Dalbavancin FDA Label [File]
  5. Dalbavancin Health Canada Product Monograph [File]

Drug created on March 19, 2008 10:17 / Updated on December 02, 2019 07:19