ISSUES OF THE OBESE DOSING. Janine Then, PharmD, BCPS

Transcription

1 ISSUES OF THE OBESE CRITICAL CARE PATIENT: DOSING Janine Then, PharmD, BCPS

2 Learning Objectives Recognize potential limitations of some routes of administration Determine optimal dosing for anticoagulation and Determine optimal dosing for anticoagulation and antimicrobials

3 Medication Administration Appropriate medication therapy for obese patients begins with the route of administration Preferred route is oral or intravenous Intramuscular injections should be avoided due to the possibility of subcutaneous administration Subcutaneous and cutaneous administration may be limited by unpredictable blood supply causing a delayed onset of action Barth M. Am J Crit Care. 2006;15:

4 Pharmacokinetic Alteration Obesity changes all aspects of pharmacokinetics Adsorption Distribution Metabolism Excretion

5 Adsorption Predicted increases in adsorption have not been proven in studies Changes in adsorption are based on anatomy changes S/p Roux-en-Y gastric bypass S/p Gastric banding No surgical interventions Lee J. Orthopedics 2006;29:

6 Distribution Obesity increases: Adipose tissue Organ mass Lean body mass Blood volume Alpha-1 acid glycoprotein Dose adjustment based on distribution depends on the properties of the drug Aminoglycosides dosed on adjusted body weight Propofol o dosed based on actual body weight Lee J. Orthopedics 2006;29:

7 Metabolism Increased blood volume seen in obesity, leads to increased blood delivery to the liver and kidneys Both phase I and phase II reactions are increased in obesity Subtherapeutic drug levels may result from standard dosing Ex LMWH are recommended to be dosed BID Fatty infiltration of the liver may or may not affect drug metabolism Lee J. Orthopedics 2006;29: Hirsh, et al. Chest 2008; 133:71S-105S

8 Excretion Conventional equations to estimate CrCl may be inaccurate in obesity Cockcroft-Gault does not account for the changes in the muscle mass to body weight ratio seen in obesity Salazar-Corcoran may be more accurate and has demonstrated a 24% increase in clearance Dosing adjustments based on the increased clearance should be medication specific Lee J. Orthopedics 2006;29:

9 What Weight Should I use to Choose a Drug Dose? Which weight is used to dose a medication is based on the drug s properties Vancomycin is dosed based on total body weight Ideal body weight (IBW) should be used for aminoglycosides until the patient exceeds 120% of their ideal weight, then use adjusted weight Adjusted body weight for aminoglycosides gy = (total body weight-ibw)x0.4 + IBW

10 Anticoagulation Prophylaxis py dosing Dalteparin has demonstrated efficacy up to a BMI of 40 kg/m 2 Bariatric surgery literature has recommended Enoxaparin 40 mg SQ q12 for a BMI of kg/m 2 Enoxaparin 60 mg SQ q12 for a BMI >50 kg/m 2 A single study in medical patients showed that enoxaparin 0.5 mg/kg SQ daily demonstrated peak anti-xa levels within in the target range Despite being a small study they did not demonstrate a correlation between anti-xa levels and body weight or BMI Spyropoulos et al. Am J Med. 2009;122: Rondina et al. Thromb Res. 2010;125: Hirsh, et al. Chest 2008; 133:71S-105S

11 Anticoagulation Therapeutic dosing Retrospective review of heparin dosing without dosing limits found No difference in percentage of patients within range at the first aptt between obese and non-obese patients A higher BMI predicted a supratherapeutic first aptt A subgroup analysis of CRUSADE (enoxaparin for NSTEMI) found that patients weighing >150kg were significantly more likely to bleed than patients weighing <150 kg American College of Chest Physicians has no firm recommendations regarding dosing in obesity They do recommend monitoring anti-xa levels els as necessary Honiden. Clin Chest Med. 2009;30: Bauer et al. Mayo Clin Proc. 2009;84: Spinler et al. Pharmacotherapy. 2009;29:

12 Antimicrobial Medication Proper dosing of antimicrobial medications is necessary for eradication and to prevent resistance Obese patients in multiple studies appear to be at higher post-surgical infection risk A small pilot study found that cefuroxime 1.5g preoperatively did attain adequate tissue concentrations for gram positive organism but not for gram negative organisms Cefazolin 2g IV pre-operatively has also been recommended due to serum levels below the organism s MIC with a 1g dose Falagas. Lancet. 2010;375: Barbour A, et al. Int J Antimicrob Agent. 2009;34: Forse RA. Surgery. 1989;

13 Antimicrobial Medication Flouroquinolones are another class that may require adjustment based on body weight Cipro has been dosed at 5 mg/kg/dose based on both adjusted and total body weight with success Vancomycin should be dosed based on total body weight and consideration should be given to q8h dosing due to increased clearance Aminoglycosides should be dosed on adjusted body weight AdjBW = (total body weight-ibw)x0.4 + IBW Honiden S. Clin Chest Med. 2009;30:

14 Summary Based on changes in the obese patient Routes of medications may be less appropriate Standard dosing may be excessive or under dosing may occur Patients should be monitored closely for therapeutic effects of drugs and toxicities Future needs More clinical trials determining the best dose for obese patients to maximize effectiveness and minimize toxicity Possible need for more pre-made dosage strengths to accommodate larger patients

15 References Barbour A, Schmidt S. Rout WR, Ben-David K, Burkhardt O, Derendorf H. Soft tissue penetration of cefuroxime determined by clinical microdialysis in morbidly obese patients undergoing abdominal surgery. Int J Antimicrob Agent. 2009;34: Barth MM, Jenson CE. Postoperative nursing care of gastric bypass patients. Am J Crit Care. 2006;15: Bauer SR, Ou NN, Dreesman BJ, Armon JJ, Anderson JA, Cha SS, Oyen LJ. Effect of body mass index on bleeding frequency and activated partial thromboplastin time in weight-based dosing of unfractionated heparin: a retrospective cohort study. Mayo Clin Proc. 2009;84: Falagas ME, Karageorgopoulos DE. Adjustment of dosing of antimicrobial agents for bodyweight in adults. Lancet. 2010;375: Honiden S, McArdle JR. Obesity in the intensive care unit. Clin Chest Med. 2009;30: Lee JB, Winstead PS, Cook AM. Pharmacokinetic alterations in obesity. Orthopedics. 2006;29:

16 References Polotsky HN, Polotsky AJ. One size may not fit all: pondering antibiotic dosing in obesity. Maturitas. 2010, doi: /j.maturitas /j Rondina MT, Wheeler M, Rodgers GM, Draper L, Pendleton RC. Weight-based dosing of enoxaparin for VTE prophylaxis in morbidly obese, medically-ill patients. Thrombosis Research. 2010;125: Schentag JJ. Antibiotic dosing does one size fit all? JAMA. 2998;279: Spinler SA, Ou FS, Roe MT, Gibler WB, Ohman, EM, Pollack CV, Alexander KP, Perteson ED. Weight-based dosing of enoxaparin in obese patients with non- ST-segment elevation acute coronary syndromes: results from the CRUSADE initiative. Pharmacotherapy. 2009;29: Spyropoulos AC, Mahan C. Venous thromboembolism prophylaxis in the medical patient: controversies and perspectives. Am J Med. 2009;122: