Drug Dosing in Geriatric Patients MK Compounding and Dispensing Antonius NW Pratama Bag Farmasi Klinik dan Komunitas Fakultas Farmasi Universitas Jember.

Drug Dosing in Geriatric Patients

MK Compounding and DispensingAntonius NW Pratama

Bag Farmasi Klinik dan KomunitasFakultas Farmasi Universitas Jember

Geriatric Patients• Geriatric patients: usually those > 65 yo• “Frail” older people with multiple comorbidities

– Frail: “weak or unhealthy, or easily damaged, broken or harmed” (Cambridge Advanced Learner’s Dictionary, 3rd ed)

• Characteristics of frailty:– High susceptibility to disease– Impending decline in physical function– High risk of death

• The frailty syndrome: – An excessive reduction of lean body mass, – a reduction in walking performance and mobility, – and poor endurance associated with a perception of exhaustion and

fatigue.

(Hilmer et al., 2007)

Key Steps in Prescribing for Geriatric Patients

• In Australia, the Quality Use of Medicines Framework:1. decide what the best treatment is (i.e. use non-

pharmacological management options first); 2. select medicines wisely (based on the suitability

of the patient); 3. use medicines based on the best evidence (the

right dose and duration)

(Hilmer et al., 2007)

http://www.health.gov.au/internet/main/publishing.nsf/content/nmp-quality.htm

Challenges in Older People

• comorbidity,• limited evidence for efficacy, • increased risk of adverse drug reactions, • polypharmacy, and • Altered pharmacokinetics.

(Le Couteur et al., 2004)

Comorbidity

(Barnett et al., 2012)

Comorbidity

(Barnett et al., 2012)

Comorbidity

(Barnett et al., 2012)

Limited evidence for efficacy

• Infrequently recruited into clinical trials• Some clinical trials probably only recruit

atypical healthy older people.• Extrapolation

(Le Couteur et al., 2004)

Limited evidence for efficacy

(Le Couteur et al., 2004)

Limited evidence for efficacy

(Le Couteur et al., 2004)

Increased risk of ADR

• Well established relationship– Hospital admission due to ADR in older people: 4x

risk– For every dollar spent on medications in aged care

nursing facilities, $1.33 is required for the treatment of drug related morbidity and mortality.

– 50% ADR in older people is preventable by better prescribing.

(Le Couteur et al., 2004)

Polypharmacy

• The use of five or more medications – occurs in 20–40% of older people.

• Risk factors: – patient age,– comorbidity, – however, the main risk factor is the prescribing doctor.

• Several negative outcomes: – ≥ 6 meds: increased 3-4-fold with ADR in as many as 81% of

patients – ≥ 4 meds: 2-fold increase of risk of falling and of recurrent

falls

(Le Couteur et al., 2004)

Altered pharmacokinetics

• Traditionally, it has been proposed that the dosage of many drugs should be reduced in older people to compensate for the age related changes in pharmacokinetics.

(Le Couteur et al., 2004)

Altered pharmacokinetics

• CLINICAL IMPLICATIONS ARE THOUGHT TO BE MINIMAL FOR:– Age-related changes occuring in: • drug absorption from the gut, • protein binding, • and volume of distribution.

(Le Couteur et al., 2004; Hilmer et al., 2007)

Altered pharmacokinetics

• Reduced hepatic metabolism of many drugs, up to 30–50% of reduction in some cases.

• Causes: age-related changes in: – hepatic blood flow, – liver mass, – and the hepatic endothelium

• May not be the cause: age-related changes in drug metabolising enzymes or their expression

(Le Couteur et al., 2004)

Renal Functions

• Filtration• Secretion• Reabsorption• Endocrine and metabolic function

• All of them are related to Glomerular Filtration Rate (GFR)

• GFR: current best indicator of kidney function

(Dowling, 2008)

Renal Functions

(Dowling, 2008)

Renal Function Estimates

• Measured Creatinine Clearance– 24-h urine collection & blood sample, result in mL/min

• Estimated Creatinine Clearance– Cockroft and Gault (1976), result in mL/min

• Estimated Glomerular Filtration Rate– MDRD4 (2007), CKD-EPI (2009), result in mL/min/1.73

m2

(Dowling, 2008; Jones, 2011)

Renal Function EstimatesCockcroft-Gault

(Jones, 2011)

With: Serum creatinine concentration (S Creat) in μmol/L; Weight (Wt) in kg; Height (Ht) in cm; Age in years

Renal Function EstimatesMDRD & CKD-EPI

(Jones, 2011)

With: Serum creatinine concentration (S Creat) in μmol/L; Weight (Wt) in kg; Height (Ht) in cm; Age in years

Renal Function Estimates

(Jones, 2011)

With: Serum creatinine concentration (S Creat) in μmol/L; Weight (Wt) in kg; Height (Ht) in cm; Age in years

(Dowling, 2008)

(Dowling, 2008)

(Munar & Singh, 2007)

Reference for Dosing Adjustment

• McEvoy G, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, Inc; 2009.

• Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults. 5th ed. Philadelphia, PA: American College of Physicians; 2007.

• Klasco RK (Ed): DRUGDEX® System (electronic version). Thomson Micromedex, Greenwood Village, Colorado,USA.

• Drug Fact and Comparisons. eFacts [serial online], Wolters Kluwer Health, Inc., St. Louis, MO.

(Munar & Singh, 2007)

(Munar & Singh, 2007)

(Munar & Singh, 2007)

http://www.kidney.org/professionals/KDOQI/gfr_calculator

http://www.niddk.nih.gov/health-information/health-communication-programs/nkdep/lab-evaluation/gfr-calculators/Pages/gfr-calculators.aspx

Ref• Barnett, K, Mercer, SW, Norbury, M, Watt, G, Wyke, S, Guthrie, B. 2012.

Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study. Lancet . 380. 37–43

• Dowling, TC. 2008. Quantification of Renal Function. in Dipiro, JT, Talbert, RL, Yee, GC, et al. (Eds.). Pharmacotherapy A Pathophysiologic Approach. 7th Ed. 705-722. New York: McGraw-Hill

• Hilmer, SN, McLachlan, AJ, Le Couteur, DG. 2007. Clinical pharmacology in the geriatric patient. Fundamental & Clinical Pharmacology. 21. 217–230

• Jones, GRD. 2011. Estimating Renal Function for Drug Dosing Decisions. Clin Biochem Rev. 32. May 2011. 81-88

• Le Couteur, DG, Hilmer, SN, Glasgow, N, Naganathan, V, Cumming, RG. 2004. Prescribing in older people. Australian Family Physician.33(10)

• Munar, MY, Singh, H. 2007. Drug Dosing Adjustments in Patients with Chronic Kidney Disease. Am Fam Physician. 75.1487-96

TERIMA KASIH