File - Dr Sam`s Rotation

Report
Dalvance
(Dalbavancin)
A new once-weekly Lipoglycopeptide
Antibiotic
Prepared by:
Kamaldeep Kainth, PharmD 2015
Objectives:
● To define what is MRSA
● To explain current medications for
MRSA infection
● To introduce Dalbavancin
● To describe the dosage, storage,
Administration, ADRs of Dalbavancin
● To evaluate ABSSSI Trials: Results
● To describe treatment Comparison
● To review prevention of Staph.
infection.
Patient Case:
CA is a 33 y/o male football player admitted to the ER with
complaints of fever, inability to walk, Erythema, local
swelling and pain on the left leg for about 5 days. His
medical history was unremarkable.
Physical examination: Wt 180lb, Ht 6ft, T 101.5F, Pain
6/10, local tenderness, restricted leg movement.
Labs: SCr 0.9, Glu 101, Hg 12.1, WBC 20, CRP 60.
Other labs: WNL
Needle Aspiration: GP cocci
The patient was initially treated with Cefazolin 3gm/day
Patient Case: 2 Days Later...
There was no improvement after 2 days of
treatment. CA still have fever of 102 and his
WBCs are now 25000. Both the needle aspirate
and bone culture grew MRSA.
How would you treat this patient???
What is MRSA??
MRSA is….
Methicillin Resistant Staphylococcus Aureus.
Staphylococcus Aureus, or simply referred as
Staph. are bacteria commonly carried on skin
or in the nose of healthy person.
When staph becomes resistant to Methicillin or
Oxacillin antibiotic then its called MRSA...
Infections caused by MRSA:
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Skin and soft tissue infection (most common)
Wound (Traumatic)
Urinary Tract Infection
Osteomyelitis
Bacteremia
Pneumonia (Less common)
Risk Factors:
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Recurrent skin disease or open wound
Long term illness or patients on dialysis
Illicit drug use (Injectables)
Surgery
Recent hospitalization.
Recent Antibiotic use
Living in crowded settings
Diagnosis:
...To make a definitive diagnosis and
confirm that Staph is the bacteria
causing the infection, culture is usually
done…
...In the past, most serious Staph
bacterial infections were treated with
penicillin type antibiotics or a
cephalosporins..
What is common among these??
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Vancomycin
Daptomycin
Linezolid
Clindamycin
Tigecycline
Synercid (Quinupristin/Dalfopristin)
Telavancin
Rifampin
Ceftaroline
What’s
New??
Dalbavancin
for injection..
Now Approved for Treatment for Acute
bacterial skin and skin structure
infections…
May 2014….
Introduction:
...Dalbavancin is second-generation
semisynthetic lipoglycopeptide antibiotic.
...Because of its longer half-life (t1/2 of 6 10 days) it is dosed once weekly.
A complete course of therapy consist of 2
single weekly doses administered on Day 1
and Day 8….
Spectrum of Activity:
● GRAM POSITIVE ORGANISMS:
o
o
o
o
o
o
o
Staphylococcus Aureus (MSSA and MRSA)
Streptococcus pyogenes
Streptococcus agalactiae
Streptococcus anginosus group (S. anginosus, S.
intermedius, S. Constellatus)
Enterococcus faecium (Only vanco susceptible strains)
Enterococcus faecalis (Only vanco susceptible strains)
Also effective against some resistant strains of
Streptococcus, Peptostreptococcus species,
Clostridium species and Actiniomyces species.
Mechanism of Action:
Bactericidal
..Dalbavancin interferes with the
transpeptidation and transglycosylation step in
cell wall synthesis mediated by binding to D-ala
D-ala terminus. Binding to this substrate inhibits
the cross-linking reactions that strengthen the
bacterial cell wall…..
Dosage and Administration:
● Acute Bacterial Skin and Skin structure
Infection in Adults
● 500mg vial available as sterile powder.
● 1000 mg given IV over 30 minutes on day 1
● 500 mg given IV over 30 minutes on day 8
● Must be reconstituted with sterile water for
injection and diluted only with 5% dextrose.
Renal Impaired: CrCl <30ml/L→ Administer 750
mg on day 1, followed one week later 375 mg
Reconstitution and Storage:
Each 500 mg vial must be reconstituted with 25
ml of sterile water for injection, USP. The
reconstituted solution can then be diluted or
transferred to iv bag of 5% Dextrose solution to
a final concentration between 1mg/ml to
5mg/ml.
Storage: Refrigerated→ 2 - 8 C (36-46 F)
Controlled Room temperature→ 20-25 C (6877F)
DO NOT FREEZE
**Total time from reconstitution to dilution to
administration should not exceed 48 hours.**
Adverse Effects:
Common AEs:
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Constipation (18.2%)
Diarrhea (4.4%)
Nausea (5.5%)
Headache (4.7%)
Serious AEs:
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C. Diff Colitis (<2%)
GI Hemorrhage (<2%)
Infusion reaction (<2%)
Hepatotoxicity (<2%)
Pregnancy Category: C
Drug Interactions:
Dalbavancin is not affected by coadministration of known CYP450 substrates,
inducers or inhibitors….
Clinical Studies: ABSSSI Trials
→ 2 Trials performed with total of 1312
randomized patients. The specific infections in
these trials were Cellulitis (50%), Major
abscess (30%) and wound infections (20%).
→ Baseline signs and symptoms of infection
included: Temperature 38C or higher, WBC
12000 or higher or 10% or more bands.
→ The mean age was 50 years and mean BMI
was 29.1 kg/m2
→ Primary endpoint was clinical response rate
defined as no increase from baseline in lesion
area after 48 to 72 hours and T at or <37.6C
Clinical studies:
Clinical Response rate in the trials at 48 to 72
hours after initiation of therapy
Dalavancin
n/N(%)
Vancomycin/Lin Difference 95%
ezolid n/N (%)
CI
TRIAL 1
240/288
(83.3%)
233/285
(81.8%)
1.5% (-4.6,
7.9)
TRIAL 2
285/371
(76.8%)
288/368
(78.3%)
-1.5% (-7.4,
4.6)
Dalavance Group: 1000 mg followed 1 week
later 500mg. (Dose adjusted for CrCl)
Vanco/Linezolid: iv vanco 1000 mg or 15 mg/kg
q 12 h. with option to switch to oral linezolid
after 3days.
Clinical Studies: Secondary end
point:
→ Patients who had reduction in lesions by 20% or
greater in 48 to 72 hours after initiation of therapy
Dalavance n/N
(%)
Vanco/Linezolid Difference
n/N(%)
(95% CI)
TRIAL 1
259/288
(89.9%)
259/285
(90.9%)
-1.0% (-5.7,
4.0)
TRIAL 2
325/371
(87.6%)
316/368
(85.9%)
1.7% (-3.2, 6.7)
ADRs:
..In the Clinical trials, the treatment related
ADRs for Dalbavancin was 12.3% and for
Vanco/Linezolid was 18.3%.
**ADRs in > or =3% of patients in Dalbavancin
included: Nausea, Diarrhea, Headache,
Pruritus.
Discontinuations:
● D → 1.8%
● V/L → 2.1%
Results:
→
The study results concluded that
Dalbavancin is non-inferior when
compared to standard drug therapy
(Vancomycin/Linezolid) in Acute
Bacterial skin and skin structure
infection….
Back to our Patient:
CA is a 33 y/o male football player admitted to
the ER with complaints of fever, inability to
walk, Erythema, local swelling and pain on the
left leg for about 5 days. His medical history
was unremarkable.
There was no improvement after 2 days of
treatment with Cefazolin. CA still have fever of
102 and his WBCs are now 25000. Both the
needle aspirate and bone culture grew
MRSA…
What would be the treatment therapy???
Treatment Options:
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Vancomycin <<<
Daptomycin
Linezolid
Clindamycin**
Tigecycline
Synercid (Quinupristin/Dalfopristin)
Telavancin
Rifampin
Ceftaroline
Dalbavancin <<<
**CA MRSA only
CO$T>>>>
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Vancomycin >>> (750mg/150ml IV $86.98)
Daptomycin >>>(500mg IV $403)
Linezolid >>> (600mg/300ml IV $167.35)
Clindamycin>> (900mg/50ml IV $9.62)***
Tigecycline>> (500mg/100ml IV $1216)
Synercid (Quinupristin/Dalfopristin)
>>>(350/150mg per vial $307.30)
Telavancin >>>>(750mg IV $358.80)
Rifampin >>> (600mg IV $136.35)
Ceftaroline >>> (600mg IV $758)
Dalbavancin<< (750mg vial $1000-$3000)#
***CA-MRSA only
Precautions
to prevent Staph.
Infection...
Can I protect myself from
becoming infected?
● WASH YOUR HANDS
● If no visible dirt, use alcohol-based hand
sanitizer
● Keep cuts and abrasions covered
● Avoid contact with other people’s wounds
● Avoid skin-to-skin contact with infected
persons
● Do not share personal items
● Clean objects and other shared surfaces
How to keep it from
spreading to others?
● Keep infected areas covered
● Follow doctor’s instructions
● Wash hands
● Put disposable waste in a separate trash
bag and close tightly before throwing it out
● Wear gloves
● Do not share personal items
● Avoid participating in contact sports
Conclusion:
Dalbavancin
Vancomycin
→ 2 Dose Regimen for SSTI
→ Dosed more frequently (qd to q 8 h)
→ Safety not established in Pediatrics
→ Established use in neonates, infants
and children.
→ Headache, GI SEs, Hepatic and
infusion related SEs (>30min)
→ Nephrotoxicity, Ototoxicity,
Neutropenia, infusion related (>60mins)
→ Pregnancy Category : C
→ Pregnancy Category : C
→ Half-life : 6 to 10 days
→ Half-life 4 to 6 hours.
→ Monitoring: Improvement, Diarrhea,
Hypersensitivity reaction
→ Culture, CBS, Improvement, Trough
levels, Renal function, Dose
adjustments**
→ Cost: $$$$
→ Cost: $$
References:
● http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingM
aterials/Drugs/Anti-InfectiveDrugsAdvisoryCommittee/UCM390793.pdf
● http://www.webmd.com/skin-problems-and-treatments/understandingmrsa-detection-treatment
● http://www.cdc.gov/mrsa/
● http://www.webmd.com/a-to-z-guides/video/truth-about-mrsa
● http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingM
aterials/Drugs/Anti-InfectiveDrugsAdvisoryCommittee/UCM390793.pdf
● http://www.medscape.org/viewarticle/518862_16
● http://content.stockpr.com/duratatherapeutics/files/docs/Dalvance+APPRO
VED+USPI.PDF
● http://www.duratatherapeutics.com/news-media/pressreleases/detail/333/durata-therapeutics-announces-phase-3-clinical-trial
● http://www-micromedexsolutionscom.proxy.westernu.edu/micromedex2/librarian/PFDefaultActionId/evidenc
expert.ShowDrugCompareResults

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