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

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

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

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

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

Patient Demographics

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

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

Causality: Unintentional Cases

Acute Exposure (< 7 days)

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

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

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%)

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%)

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

Multiple Risk Factors

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

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

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

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.

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