1. Dosage Calculations Mark Wagner, PharmD Kirollos Hanna, PharmD, BCPS PGY-2 Oncology Resident St. Luke’s Mountain States Tumor Institute March 5 th, 2016

2. Disclosures We do not have any conflicts of interest or disclosures to make No medications will be discussed off-label

3. Learning Objectives Demonstrate the importance of calculations in pharmacy practice. Calculate patient specific parameters effecting drug therapy. Solve dosage calculations for common pharmaceuticals.

4. Pharmaceutical Calculations Includes areas in: Chemical and physical properties of drugs Drug absorption, metabolism, distribution, and excretion (Pharmacokinetics) Statistical data for trials Drug development and formulations Drug dosage, dosage regimens, and patient compliance Pharmacoeconomics

5. Pharmaceutical Calculations Ensures: Patient safety Appropriate dosing Prevent toxicity Ensure therapeutic benefits Appropriate admixtures Concentrations Ratios Proportions Cost Benefit

6. Approaching Calculations 1.Take the time to read and consider computations. 2.Estimate the quantity and units of measure to satisfy the question. 3.Perform calculations using methods for efficiency and understanding. 4.Read the problem again and recheck calculations. 5.Consider the reasonableness of the answer.

7. Patient Specific Calculations Dosage Calculations

8. Patient: SM SM is a 64 year old female patient (height 5’5’’, weight 205 pounds) hospitalized for nosocomial pneumonia which is responding to treatment. Her current antibiotic medications include ceftazidime and imipenem. Her physician wishes to initiate vancomycin at a loading dose of 15 mg/kg and monitored by pharmacy. Her morning lab values include: Na 140 mEq/L K 4.0 mEq/L BUN 60 mg/dL Scr 2.7 mg/dL Glucose 222 mg/dL

9. Height & Weight Calculations Pounds (lb) to Kilograms (kg) Ideal body weight Inches (In) to Centimeters (cm) Body surface area Kidney Function

10. Pounds to Kilograms ÷ 2.2

11. Example Problems How much would a 100 lb male weight in kg? How much would a 500 lb female weight in kg? How much does 1000 grams weight in kg?

12. Example Problems Answers How much would a 100 lb male weight in kg? 45.4545454545 kg How much would a 500 lb female weight in kg? 227.2727272727 kg How much does 1000 grams weight in kg? 1 kg!!!

13. Ideal Body Weight (IBW) Healthy weight for a person Useful for medications that do not distribute to fat IBW (male) = 50kg + [(2.3kg) (each inch above 5’)] IBW (female) = 45.5kg + [(2.3kg) (each inch above 5’)]

14. Calculate SM’s IBW (height 5’5’’)

15. 45.5 + [(2.3) x 5] 45.5 + 11.5 57 kg Is SM a healthy weight?

16. Inches to Centimeters X 2.54

17. Example Problems Convert the height of a 6’ male to centimeters. How many centimeters would a 3’5’’ female be? If an infant is 2’ & 5 cm, how many cm is he?

18. Example Problems Answers Convert the height of a 6’ male to centimeters. 182.88 cm How many centimeters would a 3’5’’ female be? 104.14 cm If an infant is 2’ & 5 cm, how many cm is he? 65.96 cm

19. Body Surface Area (BSA) 1 BSA (m 2 ) = 0.007184 x Height(cm) 0.725 x Weight(kg) 0.425

20. Renal Function Poor renal function leads to decreased drug clearance. Aids in appropriate dosing for toxicity prevention. No benefit for patients with End Stage Renal Dysfunction (ESRD). Must have: Height, weight, age, and serum creatinine (SCr)

21. Renal Function Creatinine Clearance vs. Glomerular Filtration Rate Creatinine Clearance (CrCl) Exceeds GFR Creatinine is secreted by the proximal tubule as well as filtered by the glomerulus. Measured by blood tests and urine tests Glomerular Filtration Rate (GFR) 2 Cannot be measured directly Filtration marker (inulin, iothalamate or iohexol) is the gold standard for measurement – not typically used in practice Creatinine has traditionally been used to estimate GFR Adjusted to BSA. Kidney function is proportional to kidney size, which is proportional to body surface area.

22. KDOQI Stages 3,4 StageGFR*DescriptionTreatment stage 190+ Normal kidney function but urine findings or structural abnormalities or genetic trait point to kidney disease Observation, control of blood pressure. 260-89 Mildly reduced kidney function, and other findings (as for stage 1) point to kidney disease Observation, control of blood pressure and risk factors. 3A 3B 45-59 30-44 Moderately reduced kidney function Observation, control of blood pressure and risk factors. 415-29Severely reduced kidney function Planning for endstage renal failure. 5 <15 or on dialysis Very severe, or endstage kidney failure (sometimes call established renal failure) Treatment choices.

23. Renal Function 5 Creatinine Clearance (140 – patient age) x Weight (kg) 72 x SCr (mg/dL) Female = CrCl x 0.85

24. Example Problems Female, 64 years old, 5’5’’, 205 pounds, Scr 2.7 mg/dL 1.Calculate SM’s renal function using the Cockcroft and Gault equation and her actual body weight. 2.Calculate SM’s renal function using the Cockcroft and Gault equation and her ideal body weight.

25. Example Problems Answers 1.Calculate SM’s renal function using the Cockcroft and Gault equation and her actual body weight. CrCl = 30.96 ml/min 2.Calculate SM’s renal function using the Cockcroft and Gault equation and her ideal body weight. CrCl = 18.94 ml/min

26. Drug Specific Calculations Dosage Calculations

27. Drug Dosing Differences Pediatrics WEIGHT & AGE BASED DOSING!!! Adults Standard flat dosing Atorvastatin Height/weight based dosing Gemcitabine Multi-step dosing Vancomycin

28. Pediatric Dosing Not Small Adults!!!! Specific dosing for almost all drugs Age and weight are crucial Determine appropriate dosage form (i.e. liquid, tablet, etc.) Acetaminophen 10-15 mg/kg every 6 hours as needed Steps to solve Determine patient’s weight Multiply by 10-15 mg/kg Determine route of administration Calculate volume/dose for product http://sunvalleypediatricdentistry.com/tag/arizona-pediatrics/

29. Acetaminophen Problem TW’s 3 year old son AW is currently in your pediatric unit after having developed a fever and possible infection. He is having a fever and the nurses have asked the physician to order acetaminophen to bring the fever down. The physician gives a verbal order to the nurse for acetaminophen pharmacy to dose. The patient weighs 26 lbs and the standard dosing for acetaminophen is 10-15 mg/kg every 6 hours as needed for fever or pain. The patient is unable to swallow tablets so you will also need to use the liquid formulation which is 160 mg/5 mL. What is the appropriate dose and volume you would order for this child, assuming a 15 mg/kg dose?

30. Acetaminophen Answer Weight = 26 lbs = 11.8 kg Dose = 11.8 kg x 15 mg/kg = 177 mg Volume = (177 mg/160 mg) x 5 mL = 5.53 mL 177 mg/5.53 mL PO every 6 hours as needed for fever

31. ADULT DOSING Flat, Height/Weight based, and Multi-Step

32. Flat Dosing Similar effect seen in majority of patients Atorvastatin 10 mg, 20 mg, 40 mg, 80 mg Based on risk factors No need for calculations http://iverson.cm.utexas.edu/courses/310N/MOTD%20Fl05/MOTDsp04/Atorvastatin.html

33. Height/Weight Based Dosing Patient’s height and weight determine how much drug is required to have similar effect BSA! Chemotherapy Gemcitabine 1000 mg/m 2 Steps to solve Determine patient’s height and weight Calculate BSA = X m 2 Multiply 1000 mg x X m 2

34. BSA Problem JN is a 73 year old male who presents with metastatic pancreatic cancer. The patient wishes to undergo palliative treatment with gemcitabine 1000 mg/m 2 weekly x7 weeks then off 1 week, followed by weekly ¾ weeks every 28 days. Patient is 5’ 8” tall and weighs 168 lbs. His renal and hepatic function are within normal limits and his labs are all okay to move forward with treatment. What dose of gemcitabine should he receive? http://www.realclearsports.com/lists/dominance_single_events/masters_jack_nicklaus.html

35. BSA Answer Height = 5’ 8” = 68” = 172.7 cm Weight = 168 lbs = 76.4 kg BSA = 0.007184 x 172.7 0.725 x 76.4 0.425 = 1.9 m 2 Dose = 1.9 m 2 x 1000 mg/m 2 = 1900 mg

36. Multi-Step Dosing Requires the use of patient’s weight, height, renal function, and possibly many other factors Antibiotics! Vancomycin Renal function, height, and weight Steps to solve Obtain patient’s height, weight, serum creatinine, causative infection, other patient factors affecting drug distribution Calculate creatinine clearance Select appropriate dosing Use the above to determine dose and frequency of dose for a given patient

37. Vancomycin Problem JS is a 21 year old who presents with a bad case of cellulitis in his left calf after a recent golf tournament down in Florida. The physician decides to use vancomycin for empiric gram + coverage and requests that pharmacy doses it. The patient is 5’ 7” and weighs 154 lbs, and his SCr is 0.9 mg/dL. All other labs are within normal limits. How would you dose the vancomycin given the following chart and dosing of 15-20 mg/kg (rounded to the nearest 250 mg increment)? St. Luke’s Regional Medical Center. Vancomycin Dosing Guidelines. Appendix E MM026 TV

38. Vancomycin Answer Height = 5’ 7” = 67 inches = 170.2 cm Weight = 154 lbs = 70 kg CrCl = ((140 – 21) x 70 kg)/(72 x 0.9 mg/dL) = 128 mL/min Dose = 15 – 20 mg/kg x 70 kg = 1050 mg – 1400 mg- middle ground ~1250 mg Frequency of dosing CrCl >100 and pt. <40 years old = every 8 hour Dose = 1250 mg IV every 8 hours

39. ADDITIONAL PROBLEMS

40. IV Fluids Determining appropriate electrolyte concentrations Custom IV bags may be necessary for certain patients Fluid restrictions 154 mEq NaCl in 1L of NS, 4 mEq NaCl in 1mL of 23.4% NaCl Steps to create custom bag Determine quantity of substance needed for final concentration to be correct Determine volume of product you need to add to give you this concentration

41. IV Fluid Problem A physician orders a 500 mL D5W ¼ NS IV infusion for a patient. Your pharmacy does not stock this formulation in a 500 mL version and the compounder is down so you must make this by hand. You have D5W 500 mL bags and 23.4% NaCl solution. What volume of NaCl needs to be added to give you the appropriate product? http://www.shopmedvet.com/category/iv-fluids

42. IV Fluid Answer NS = 0.9% NaCl = 154 mEq/L so ¼ NS = 38.5 mEq/L = 19.25 mEq/500 mL 23.4% NaCl = 4 mEq/mL 19.25 mEq/4 mEq/mL = 4.81 mL Add 4.81 mL of 23.4% NaCl to a 500 mL bag of D5W to obtain a final product of 500 mL of D5W ¼ NS

43. Conclusion Dosage calculations affect every patients life Small mistakes can lead to big problems Be vigilant!

44. Questions https://www.copera.org/resources/newsletters/elevate/summer-2015/expired-drugs-continue-use-or- discard

45. References 1.Du Bois D, Du Bois EF: A formula to estimate the approximate surface area if height and weight be known. 1916. Nutrition 5:303- 311; discussion 312-313, 1989. 2. Stevens LA, Levey AS. Measured GFR as a confirmatory test for estimated GFR. J Am Soc Nephrol. 2009;20(11):2305-2313. 3.National Kidney Foundation: K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Kidney Disease Outcomes Quality Initiative. Am J Kidney Dis. 2002;39(suppl 1):S1-266. 4.Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med. 2003;139(2):137- 147. 5.Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41