Therapeutic Drug Monitoring for Adults - Wirral University Teaching ...

Appendix I - Therapeutic drug monitoringIntroductionTherapeutic Drug Monitoring aims to individualise drug therapy and avoid both sub-therapeutic andtoxic plasma drug concentrations. A number of factors influence drug concentration and a singlesample will only reflect the concentration at the sampling time.When a new drug is introduced, ‘steady state’ will not be approached until fourelimination half-lives have elapsed. Sampling prior to this time may not be beneficialunless a problem is anticipated e.g. non-compliance or toxicity. Results must be judgedin light of clinical observations and other relevant investigations.Clinical advice and assistance can be obtained from the laboratories performing the tests. Adviceon drug dose selection and interpretation of measured plasma drug concentrations can be obtainedfrom Clinical Pharmacists or the Pharmacy Department. Drug dosing in overweight patientsExercise caution with overweight individuals where drug dosing with water-soluble agents suchas gentamicin should be based on ideal body weight.Ideal body weight (IBW)IBW Females (kg)IBW Males (kg)= [45.5 + (2.3 x every inch over 5ft)]= [50+ (2.3 x every inch over 5ft)]For dosing of water-soluble agents such as gentamicin in obese patients (actual body weight >20%above IBW) use adjusted body weight for dose calculationAdjusted body weight (kg) =Ideal body weight + 0.4 (actual body weight – ideal body weight) Estimation of renal function.Please note that renal function can be expressed as either creatinine clearance (CrCl) using a24-hour urine collection or calculated using the Cockroft and Gault formula, or estimatedGlomerular Filtration Rate (eGFR) which is calculated using the MDRD formula.eGFR estimates are reported in mL/minute/1.73m 2 . They are not the same as creatinineclearance estimates, which are reported in mL/min. eGFR estimates have not yet been validatedfor drug dosing and all dosing advice in this section is based on creatinine clearance. If youhave any questions please refer to Appendix 3 of the BNF or contact pharmacy for advice.Cockroft and Gault formula for creatinine clearance:Creatinine clearance (mL/min) = _Y x (140-age) x weight*__Serum creatinine (micromol/L)Where Y = 1.23 for males and 1.04 for femalesAge is in yearsWeight is in kg*For overweight patients use Ideal Body Weight (IBW) to calculate Cockroft and Gault- 77 -Wirral University Teaching Hospital NHS Foundation Trust April 2011

IBW Females (kg) = [45.5 + (2.3 x every inch over 5ft)]IBW Males (kg) = [50 + (2.3 x every inch over 5ft)]Calculating creatinine clearance from a 24-hour urine collection:CrCl (mL/min) = U Cr VS Cr tU Cr = urine creatinine concentration (micromol/L)V = volume of urine (mL)S Cr = serum creatinine concentration (micromol/L)t = time over which sample was collected (min)- 78 -Wirral University Teaching Hospital NHS Foundation Trust April 2011

TeicoplaninTherapeuticsDosage form: Intravenous bolus, intravenousinfusion or intramuscular injection.Loading dose:For patients 85kg give 6mg/kg every 12hours for 3 doses.Maintenance dose:For patients 85kg give 6mg/kg once daily.In some clinical situations, such as infected,severely burned patients or Staphylococcusaureus endocarditis, unit maintenance dosesof up to 12mg/kg have been administered IV.Therapeutic range: pre-dose ‘trough’>20mg/L, up to 50mg/L in resistant infections.The relationship between toxicity and serumdrug concentration is unclear but therapeuticfailures are more common with trough levels97% excretedunchanged in urine.Vd: 0.94–1.4L/kg.SamplingVolume of blood: Fill to lineTube to use: Ochre top.Lab performing assay: Royal LiverpoolUniversity Hospital (RLUH) MicrobiologyDepartment.Emergency service: No.Sampling times: The Pharmacy Departmentwill advise on levels to be taken. Troughlevels should be taken immediately before adose.RLUH will only perform assays on Mondays,Wednesdays and Fridays. Samples shouldbe sent to Wirral Clinical Biochemistry asearly as possible on these days so they cango on the transport run to RLUH.Resample time: Dependent on clinical statusof patient. In patients who require monitoring;as a guide; a trough level is usually taken onday 5 or 6 of therapy and repeated weekly iflevels are not in range.Reporting procedure: Available via PCIS.Additional InformationTeicoplanin is administered by the IV routein the treatment of endocarditis and otherserious infections caused by Gram-positivecocci including multi-resistant staphylococci.It is also used for surgical prophylaxis inpatients with a history of MRSA.Peak levels are not required.Therapeutic response usually seen in 48-72hours.Therapeutic drug monitoring may be used tooptimise therapy in burns or obese patients,patients with proven or suspected MRSAbacteraemia, patients requiring high dosetherapy for more resistant organisms,patients not responding to therapy andpatients with infective endocarditis.- 80 -Wirral University Teaching Hospital NHS Foundation Trust April 2011

VancomycinTherapeuticsDosage form: Intravenous infusion.Loading dose: See product monograph inmain Trust antibiotic formulary.Maintenance dose: See product monographin main Trust antibiotic formulary.Therapeutic range:Pre-dose ‘trough’ 10 to 15mg/L; troughconcentrations up to 20mg/L may be requiredin deep-seated or resistant infections.In MRSA bacteraemia aim for trough~15mg/L.Toxic effects: Hypotension and anaphylacticreactions occur if given too quickly. Ototoxicityand nephrotoxicity are rare, although risk isincreased if co-administered withaminoglycosides. Groups at special riskinclude patients with impaired renal functionand the elderly.PharmacokineticsElimination half-life: 6 to 10 hours (normalrenal function); up to 216 hours in end stagerenal failure.Major route of elimination: 80 to 90%excreted unchanged in urine.Vd: 0.7L/kg (0.9L/kg in ESRF)Factors affecting plasma concentration:Increased in renal impairment.Decreased in severe burns.SamplingVolume of blood: Fill to lineTube to use: Ochre or green top.Lab performing assay: Wirral ClinicalBiochemistry.Emergency service: Yes, but should not benecessary.Sampling times: The Pharmacy Departmentwill advise on levels to be taken. Troughlevels should be taken immediately before adose.Resample time: Dependent on clinical statusof patient. In patients who require monitoring;as a guide, a trough level is usually taken onday 2 or 3 of therapy and repeated weekly.Reporting procedure: Available via PCIS.Additional InformationVancomycin is administered by theintravenous route in the treatment ofendocarditis and other serious infectionscaused by Gram-positive cocci includingmulti-resistant staphylococci.Peak levels are not usually required.Oral vancomycin is not absorbed but can beused for the treatment ofpseudomembranous colitis due toClostridium difficile. Monitoring is notrequired.Intraperitoneal administration of vancomycinmay be used in the treatment of peritonealdialysis associated peritonitis. See RenalUnit guidelines for initial dose and contactthe renal pharmacists for advice onmonitoring.- 81 -Wirral University Teaching Hospital NHS Foundation Trust April 2011