1. COMPARISON OF ADVERSE EFFECT PROFILES OF PAIN REGIMENS WITH AND WITHOUT INTRAVENOUS ACETAMINOPHEN IN TOTAL HIP AND KNEE ARTHROPLASTY PATIENTS Alyssa J. Gallipani Pharm.D. PGY-1 Pharmacy Resident Monmouth Medical Center Long Branch, New Jersey 1

2. Introduction Safety and tolerability profile Efficacy of pain relief Effect on opioid use 2

3. Background Acetaminophen (Ofirmev™) injection is indicated for the management of mild to moderate pain, moderate to severe pain with adjunctive opioid analgesics, and reduction of fever 1 The goal of perioperative pain control is multimodal pain management Intravenous acetaminophen (IVA) has the potential to fill unmet needs in the perioperative setting 2 The most common adverse effects of IVA include nausea, vomiting, headache, insomnia, and pyrexia Literature regarding safety of IVA is lacking 1. Product Information. Ofirmev ® (acetaminophen) injection. Hazelwood, MO: Cadence Pharmaceuticals, Inc.; December 2014. 2. Am J Ther 2012; 19: 66-75. 3

4. Research Objective The objective of this study is to determine if there is a difference in frequency and type of adverse drug events (ADE’s) between IVA and non-IVA treated patients 4

5. Study Design Approved by Investigational Review Board Retrospective chart review March 2011 through August 2012, and February 2013 through August 2013 All patients who underwent total hip or knee replacement included 2 study groups: Those who received IVA (n=406) Those who did not receive IVA (n=203) Matched for age, gender, and procedure type 5

6. Study Design Inclusion Criteria: Total hip or total knee replacement surgery Age >18 years old Exclusion Criteria: Known allergy or hypersensitivity or contraindication to opioids or acetaminophen 6

7. Methods All data were recorded without identifiers and kept confidential Data was collected from electronic medical record (EMR) Demographics Adverse events or complaints Labs Vital signs Concurrent medications 7

8. Data Analysis Statistical Analysis: Chi squared test Race Fisher’s exact test Procedure type Adverse events Concomitant medications Comorbidities Student’s t-test Age Labs Length of stay Mean doses 8

9. Results Table 1: Demographics IVANo IVAP-value Male (%)172 (42.36)86 (42.36)1 Age; years(±SD)64.6 (±10.72)65.0 (±10.48)0.65 Total Hip Replacement (%) 158 (38.9)79 (38.9)1 Total Knee Replacement (%) 248 (61.1)124 (61.1)1 Mean length of stay; days 3.363.350.96 9

10. Results Table 2: ADE count IVANo IVAP-value Patients who experienced at least one ADE (%) 372 (91.6)172 (84.7)0.012 # ADEs per patient (%) IVANo IVA 1169 (45.4)111 (64.5) 2119 (32)40 (23.3) 351 (13.7)15 (8.7) 415 (4)4 (2.3) 515 (4)2 (1.2) 64 (1.1)0 10

11. Results Graph 1: Summary of overall ADEs 11

12. Results Table 3: Incidence of ADEs (%) IVANo IVAP Value Gastrointestinal Nausea59 (14.5)21 (10.3)0.16 Vomiting27 (6.7)14 (6.9)1 Constipation9 (2.2)50 (2.5)0.67 Neurologic Lethargy11 (2.7)4 (2)0.78 Fatigue4 (1)00.31 Dizziness19 (4.7)11 (5.4)0.69 Lightheadedness12 (3)14 (6.9)0.03 Dermatologic Rash3 (0.7)00.55 Itch8 (2)3 (1.5)0.76 Labs/Vitals LFT> ULN23 (5.7)4 (2)0.04 Hypotension339 (83.5)159 (78.3)0.12 Bradypnea117 (28.8)1 (0.5)<0.0001 12

13. Results Graph 2: Mean cumulative acetaminophen exposure per patient for entire length of stay (mg) 13 7260.1 7705.9

14. Results Graph 3: Mean cumulative opioid exposure per patient (mg) for entire length of stay 14 209.6 163.9

15. Discussion Develop guidelines for appropriate use 3 : Restrict to NPO patients Maximum number of doses per order Maximum duration of order (i.e. 24 hours) Limitations: Concomitant medications Under-reporting of ADEs Future study: Effect on pain control 3. Hosp Pharm. 2016; 51: 9-10. 15

16. Conclusion The increased utilization of IVA in multimodal pain management did not have an improved safety profile or tolerability in orthopedic patients when opioid prescribing remained unchanged 16

17. Assessment Which of the following side effects are most commonly reported with intravenous acetaminophen use? A) nausea B) vomiting C) headache D) insomnia E) all of the above 17

18. Acknowledgments Hoytin Lee Ghin, Pharm.D., BCPS A. Scott Mathis, Pharm.D. Germin Fahim, Pharm.D., BCPS Marija Markovic, Pharm.D. 18

19. References 1. Product Information. Ofirmev ® (acetaminophen) injection. Hazelwood, MO: Cadence Pharmaceuticals, Inc.; December 2014. 2. Jahr J, Breitmeyer J, Pan C, et al. Safety and efficacy of intravenous acetaminophen in the elderly after major orthopedic surgery: subset data analysis from 3, randomized, placebo- controlled trials. Am J Ther. 2012; 19: 66-75. 3. Poeran J, Babby J, Mazumdar M, et al. Survey among hospitals on strategies to ensure appropriate use of intravenous acetaminophen. Hosp Pharm. 2016; 51: 9-10. 19

20. QUESTIONS? Alyssa Gallipani, Pharm.D. PGY-1 Pharmacy Practice Resident Monmouth Medical Center, Long Branch NJ 20

21. ADE Criteria Adverse Drug EventCriteria Systolic blood pressure<90 mm Hg Diastolic blood pressure<60 mm Hg Respiratory depression< 14 breaths per minute AST> 41 units per liter ALT>43 units per liter 21