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TDM of vancomycin

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.

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TDM of vancomycin

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  1. TDM of vancomycin (Antibiotic)

  2. Introduction • Antibacterial, tricyclicglycopeptide antibiotic. • used to treat gram-positive infection caused by: - methicillinresistant staphylococci - ampicillinresistant enterococci.

  3. 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.

  4. Major brands and strengths BrandsContainsDosage forms VancardVancomycin HCl USP 500mg/vial Inj Vancomin Vancomycin HCl USP 500mg/vial or 1 g/ vial Inj Vancomycin HCl500mg/ vial Inj VanmycinVancomycin HClInj

  5. 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)

  6. Uses of vancomycin • Endocarditis • Meningitis • Osteomyelitis • Respiratory Tract Infections • Skin and skin structure infections • Clostridium difficile-associated Diarrhea andColitis • Staphylococcal Enterocolitis

  7. Administration and dosage • Administration - orally - slow infusion • Dose - Normal: 15 to 20 mg/kg - Toxicity dose: Greater than 4g/day - Staphyloccalenterocolitis: 500 mg – 2 g/day PO divided TID/QID - renal impairment: 15 mg / kg initially

  8. 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.

  9. Drug interactions • with other ototoxic and/or nephrotoxic drugs • Aminoglycosides • AmphotericinB • Bacitracin • PolymyxinB • Anesthetics

  10. Clinical pharmacokinetics Absorption IVor 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

  11. 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

  12. Clinical signs and symptoms of toxicity • red man syndrome (erythema,flushing,pruritis) • Angioedema • Leucopenia • Thrombocytopenia • Ototoxicity • Nephrotoxicity

  13. Analytical methods for vancomycin monitoring: Immunoassay: 1)microbiologic assay 2) fluorescence immune assay technique. Chromatographic methodHPLC

  14. 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

  15. 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

  16. Dosing Guidelines • Initial vancomycin doses: →actual body weight • Subsequent dosage: → actual serum concentrations

  17. Dose Normal dose 15-20 mg/kg (250 mg) IV 1000 mg NeonatesIV: Loading dose of 15 mg/kg Infants and ChildrenIV: usual start dose 15mg/kg 6 hourly Maximum recommended 2g/dose Adults 15 mg/kg (based on [ABW]/dose maximum of 2 g/dose

  18. 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.

  19. 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.

  20. 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 step maintenance dose: MD = Kel x Vd x Cptmax x (1 - e-Kel x tau / 1 - e-Kel x tinf)

  21. Continued… 2nd approachincludes: 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)

  22. 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

  23. 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/hr26 hr

  24. 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) (Cpssave) (t) / (S) (F) =(0.83 L/hr) (20mg/L) (1hr) / (1) (1) = 17 mg

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