1. Acetaminophen Overdoses: A Review of Intentional and Unintentional Cases Hospital of the University of Pennsylvania Philadelphia, PA Sarah Erush, PharmD, BCPS Karen Shalaby, PharmD

2. Hospital of the University of Pennsylvania 700 bed tertiary academic medical facility Level I Trauma Center/Transplant Services Serves tri-state region Averages 35,000 admissions per year No pediatric admissions

3. Adverse Drug Event Program Operated by Drug Information Service Averages 600 reports per year Spontaneous and targeted reporting methods Acetaminophen overdoses reported despite recommendations otherwise Unintentional overdose trend noted

4. Acetaminophen Case Series 1998 – 2002 YTD 54 Reports 52 Charts Received 49 Reviewed 47 Acetaminophen 23 Intentional 23 Unintentional 1 unknown 3 Incomplete 2 Not Acetaminophen

5. Psychiatry Consult Service 13/23 (56%)0/23 (0%)No Request: 10/23 (44%)23/23 (100%)Request: UNINTENTIONALINTENTIONAL

6. Patient Demographics

7. Acetaminophen Dose 1.1 to 180.5 to 101Range (gm/day) 6.415.6Median (gm/day) 8.132Average (gm/day) 8/23 (34%)10/23 (43%)Known 15/23 (65%)13/23 (56%)Unknown UNINTENTIONALINTENTIONAL

8. Acetaminophen Formulation INTENTIONAL RX = 3 Percocet  n=2 Darvocet  n=1 OTC =21 Single Entity n=8 Combo Entity n=13 UNINTENTIONAL RX = 3 Percocet  n=2 Darvocet  n=1 OTC = 20 Single Entity n=15 Combo Entity n=5

9. Causality: Unintentional Cases

10. Acute Exposure (< 7 days)

11. Lab Results: Average Peak Levels INTENTIONALUNINTENTIONAL APAP:115.1 mg/L27.8 mg/L ALT:3,065 units/L5,193 units/L AST:2,742 units/L6,819 units/L INR:2.54 T Bili:1.87 mg/dL5.87 mg/dL

12. Length of Stay 65Median 2 to 302 to 55Range 8.97.4TOTAL Days: Average 1 to 101 to 16Range 43Median 4.43.6ICU Days: Average UNINTENTIONALINTENTIONAL

13. Patient Outcome INTENTIONALUNINTENTIONAL Resolved:22/23 (96%)16/23 (69%) Evaluated:9/23 (39%)11/23 (48%) Transplant:0/23 (0%)2/23 (9%) Death:0/23 (0%)3/23 (13%) Transplant and Death: 1/23 (4%)0/23 (0%)

14. Risk Factors INTENTIONALUNINTENTIONAL Hepatic Disease:1/23 (4%)2/23 (9%) Alcohol Use: (Acute or Chronic) 14/23 (61%)20/23 (87%) Drug Abuse: (Current or Past) 10/23 (43%)8/23 (35%) Concomitant Disease: 1/23 (4%)3/23 (13%)

15. Alcohol Use 2/23 (9%)1/23 (5%)Unknown: 6/23 (26%)10/23 (44%)None: 6/23 (26%)3/23 (13%)Acute with Chronic: 0/23 (0%)2/23 (8%)Acute: 9/23 (39%)7/23 (30%)Chronic: UNINTENTIONALINTENTIONAL

16. Multiple Risk Factors

17. Data Summary Unintentional overdoses accounted for 50% cases Doses are lower and ingested over 1 to 3 days Unintentional cases had greater toxicity when judged by LFT, INR, and length of stay Unintentional cases had higher transplant and death rates

18. Data Summary cont. Influence of risk factors remains unclear Hospital Costs (mean) Intentional: $12,671 Unintentional: $23,380 Extrapolated Cost Data Results similar to those previously published

19. Recommendations Continue availability of OTC Acetaminophen Education of healthcare practitioners Encourage reporting of acetaminophen overdoses Awareness of unintentional overdoses Education of patients Awareness of potential toxicity

20. Recommendations cont. Labeling Maximum dose and duration Combination products Packaging Limit purchase size Consider unit dose application Manufacturing Consider addition of N-Acetylcysteine to Acetaminophen preparations.

21. Quote “If I had known it would make me this sick, I never would have taken it”