tdm of vancomycin

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TDM of vancomycin (Antibiotic)

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TDM of vancomycin. (Antibiotic). Introduction. Antibacterial , tricyclic glycopeptide antibiotic . used to treat gram-positive infection caused by: - methicillin resistant staphylococci - ampicillin resistant enterococci. Mechanism of action. - PowerPoint PPT Presentation

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Page 1: TDM of vancomycin

TDM of vancomycin(Antibiotic)

Page 2: TDM of vancomycin

Introduction

• Antibacterial, tricyclic glycopeptide antibiotic.

• used to treat gram-positive infection caused by: - methicillin resistant staphylococci - ampicillin resistant enterococci.

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Mechanism of action• Vancomycin acts by inhibiting cell wall synthesis

of bacteria. • Vancomycin binds to the building blocks of the

peptidoglycan

• it prevents the transpeptidase from acting on these newly formed blocks

• prevents cross-linking of the peptidoglycan layer.

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Major brands and strengths

Brands Contains Dosage forms

Vancard Vancomycin HCl USP 500mg/vial Inj Vancomin Vancomycin HCl USP 500mg/vial or 1 g/ vial Inj

Vancomycin HCl 500mg/ vial Inj

Vanmycin Vancomycin HCl Inj

Page 5: TDM of vancomycin

Pharmacokinetic data

• Bioavailability Negligible (oral)

• Metabolism Excreted unchanged

• Half-life 4–11 hours (adults) 6-10 days (renal impairment)

• Excretion Renal

• Volume of distribution 0.5-1 L/kg

• Clearance 7L/hr (85% renal clearance)

Page 6: TDM of vancomycin

Uses of vancomycin

• Endocarditis• Meningitis• Osteomyelitis• Respiratory Tract Infections• Skin and skin structure infections• Clostridium difficile-associated Diarrhea

andColitis• Staphylococcal Enterocolitis

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Administration and dosage

• Administration - orally - slow infusion• Dose - Normal: 15 to 20 mg/kg - Toxicity dose: Greater than 4g/day - Staphyloccal enterocolitis: 500 mg – 2

g/day PO divided TID/QID - renal impairment: 15 mg / kg initially

Page 8: TDM of vancomycin

Side effects

• Hives (Rashes)• Ototoxicity• Hypotension• Fever, chills, body aches, flu

symptoms• Red man syndrome• Anemia and insomnia in patient

older than 65 years• Nephrotoxicity and intestinal

nephritis.

Page 9: TDM of vancomycin

Drug interactions

• with other ototoxic and/or nephrotoxic drugs

• Aminoglycosides• Amphotericin B• Bacitracin• Polymyxin B• Anesthetics

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Clinical pharmacokinetics

Absorption IV or orally IM route is not used Distribution Vd is 0.5 to 1.0 l/kg Metabolism not metabolized to a greater extent 80 to 90% of IV administered drug can

be recovered unchanged in urine Excretion CLV = 0.65 xCLCr x total

body weight

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TDM of vancomycin

“measurement of medication levels in blood”

Conditions & altered PK parameters for TDM of vancomycin:

Vancomycin therapy for longer than 5 days Impaired renal function Impaired hepatic function Pregnancy Obese Severe burns Concomitant therapy with nephrotoxic drugs

Page 12: TDM of vancomycin

Clinical signs and symptoms of toxicity

red man syndrome (erythema,flushing,pruritis) Angioedema LeucopeniaThrombocytopenia Ototoxicity Nephrotoxicity

Page 13: TDM of vancomycin

Analytical methods for vancomycin monitoring:

Immunoassay: 1) microbiologic assay 2) fluorescence immune assay technique.

Chromatographic method HPLC

Page 14: TDM of vancomycin

Timing of monitoring

• Serum is preferred specimen.• Sample should be taken after

third dose (usually fourth dose)• which is obtained in 3 to 5

days

Page 15: TDM of vancomycin

precautions

• Careful observation of the patient overgrowth of non susceptible microorganisms

• monitoring of renal function (with amino glycosides)

nephrotoxicity

• periodic monitoring of the leukocyte count (In Case of prolonged therapy)

neutropenia

• vancomycin should be infused at a rate 10 mg/minute

'red-man' syndrome

Page 16: TDM of vancomycin

Dosing Guidelines

• Initial vancomycin doses: →actual body weight

• Subsequent dosage: → actual serum

concentrations

Page 17: TDM of vancomycin

Dose

Normal dose 15-20 mg/kg (250 mg) IV 1000 mg

Neonates IV: Loading dose of 15 mg/kg

Infants and Children IV: usual start dose 15mg/kg 6 hourly Maximum recommended 2g/dose

Adults 15 mg/kg (based on

[ABW]/dose maximum of 2 g/dose

Page 18: TDM of vancomycin

Dose adjustment a/c to trough levels

• dosing interval is adjusted, based on the steady state trough concentration

• trough levels >10 mg/L.(i.e. 15-20mg/L)

• Low trough levels: Increase dose and/or reduce interval (ie: give more frequently).

• High trough levels: Increase interval (give less frequently) first, and/or reduce dose.

Page 19: TDM of vancomycin

Continued…

•  Level <5 increase dose by 50-100% (eg 10 to 20 mg/kg/dose).

• Level 5-10 increase dose by 20%

• Level >20 increase dose interval (eg from 6 to 8 hourly). Recheck level prior to next dose

and administer if within target range.

Page 20: TDM of vancomycin

Dosage regimen calculation

2 approaches to calculate this. 1st approach includes:1st step pharmacokinetic parameters:

Kel = 0.009 + (CLcr x 0.0022)

Vd = DW x Vdperkg

tau = tinf + [ln(Cptmax / Cptmin) / Kel]

2nd stepmaintenance dose:

MD = Kel x Vd x Cptmax x (1 - e-Kel x tau / 1 - e-Kel x tinf)

Page 21: TDM of vancomycin

Continued…

2nd approach includes:

Creatinine Clearance Clcr (females) = (140 – age) x IBW*/Scr (μmol/L) Clcr (males) = Clcr (females) x 1.2

IBW Calculation:

IBW = 50 + 2.3 × inches over 60 (for men)

IBW = 45 + 2.3 × inches over 60 (for women)

ABW = IBW + 0.4 × actual wt – IBW DW = 0.4 (ABW – IBW) + IBW (if ABW

> IBW)

Page 22: TDM of vancomycin

Case study

B.C., > a 65 - year old , > 45 kg male

past medical history: > diabetes mellitus, > hypertension > hospital-aquired , nafcillin-resistant S.aureus

infection . > serum creatinine of 2.2 mg / dL, >.( Note that Vd = 0.7L/kg ) > Cpss (avg) = 20 mg/L

 

Page 23: TDM of vancomycin

calculation of the pharmacokinetic parameters Vd = DW x Vdperkg

= 0.7 L / kg. * 45 kg. 31.5 L

CLcr = (140 – Age ) (weight) / (72) (SrCrss) = (140 – 65 ) (45)/ (72) (2.2) 21.3 ml/min

Cl = (0.65)(CLcr )*(total body wt) =(0.65)(0.475 ml/kg/min)(45 kg) 0.83 L/h

Kd = Cl / Vd = 0.83 L/h / 31.5 L 0.026 hr -1

t 0.5 = (0.693) (Vd) / Cl = (0.693) (31.5 L) / 0.83 L/hr 26 hr

Page 24: TDM of vancomycin

Further calculations

Initial plasma concentration: Cpo = (S) (F) (loading dose) / Vd = (1) (1) (15 mg/kg) / 0.7 L/Kg = 21 mg/L ~20mg/L

Loading Dose : Loading dose = (Vd) (Cp) / (S) (F) = (31.5 L) (30 mg/L) / (1) (1) = 945mg or ~1000mg

Maintenance Dose : Maintenance dose = (Cl) (Cpss ave) (t) / (S)

(F) =(0.83 L/hr) (20mg/L) (1hr) / (1)

(1) = 17 mg

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