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Guidelines for the Management of Acetaminophen Overdose

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Guidelines for the Management of Acetaminophen Overdose Guidelines for the Management of Acetaminophen Overdose PROFESSIONAL PRODUCT INFORMATION Guidelines for the Management of Acetaminophen Overdose This brochure outlines basic steps in the management of acetaminophen overdose and reviews the application of these management principles to special populations. It is a revision of previous publications and should be used in place of earlier versions. Included herein are flowcharts for managing both acute and chronic acetaminophen overdose, and a nomogram, which uses acetaminophen serum concentrations at various time intervals following a single, acute overdose to determine whether the antidote should be administered. In January 1985, the United States (US) Food and Drug Administration If you would like additional information about TYLENOL® (acetamino- (FDA) approved the oral administration of acetylcysteine (N-acetylcys- phen), or additional copies of this management protocol, please contact teine, NAC) as an antidote for the treatment of acetaminophen overdose. us at the address below. Approval of acetylcysteine for this purpose was based on a nationwide research program conducted by the Rocky Mountain Poison and Drug Center under the sponsorship of McNeil Consumer Healthcare. This McNeil Consumer Healthcare research clearly demonstrated the efficacy of acetylcysteine, when used early in the course of treatment, in reducing morbidity and virtually elim- 7050 Camp Hill Road inating mortality associated with acetaminophen overdose. In 2004, the Fort Washington, PA 19034 FDA approved the intravenous formulation of acetylcysteine (Acetadote®, Cumberland Pharmaceuticals, Nashville, TN). (482) Prepared by the consultant panel: This monograph is intended to assist practitioners in managing acet- aminophen overdoses and is not meant as a standard of care. For further G Randall Bond, MD information concerning complex or difficult cases, please contact your E. Martin Caravati, MD, MPH local poison center (1-800-222-1222) or a clinical toxicologist. McNeil Con- Richard C. Dart, MD, PhD sumer Healthcare sponsors a toll free telephone number (1-800-525-6115), Kennon Heard, MD available 24 hours a day, at the Rocky Mountain Poison and Drug Center. Robert S. Hoffman, MD Please do not hesitate to use these resources if you need individualized Barry H. Rumack, MD consultation on managing a patient with an acetaminophen overdose. Wayne R. Snodgrass, MD, PhD With support from McNeil Consumer Healthcare Division of McNEIL-PPC, Inc. (acetaminophen) 38 Table of Contents Guidelines for the Management Management of Repeated Chronic of Acetaminophen Overdose 38 Supratherapeutic Ingestion 47 Table of Contents 39 Clinical Characteristics of Acute Acetaminophen Overdose 48 Introduction 40 Phase I 48 Definitions 41 Phase II 48 Phase III 48 Management of Acute Overdose 42 Summary 49 1. Initial Assessment 42 2. Gastric Decontamination/Prevention of Absorption 42 Acetaminophen Overdose: 3. Determining the Need for Acetylcysteine 43 Suggested Readings 54 Acetaminophen Assay ...............................43 List of Figures, Flowcharts, and Charts 4. Administration of Acetylcysteine 43 a. Choose a route of administration ...................43 Flowchart 1. Stepwise Management of Acute Acetaminophen Overdose 50 b. Transitioning from oral to intravenous acetylcysteine treatment. 44 Flowchart 2. Stepwise Management of Repeated Supratherapeutic Ingestion 51 c. Continuation of acetylcysteine treatment ...........44 Chart 1. Rumack-Matthew Nomogram 52 5. Other Laboratory Tests 44 Chart 2. Common Adverse Events Associated 6. Supportive Treatment 44 with the Oral and Intravenous Formulations 7. Special Considerations 45 of n-acetylcysteine. 53 a. Extended release acetaminophen ...................45 b. Ingestion of acetaminophen combination products . 45 c. Massive acetaminophen ingestion ..................45 d. Intravenous acetaminophen ........................45 8. Special Populations 46 a. Young children (<6 years of age) ....................46 b. Pregnant women ..................................46 c. Patients presenting 24 hours or more postingestion ..46 d. Chronic alcohol users ..............................46 e. Obese patients ....................................46 f. Other diseases .....................................46 (acetaminophen) 39 Introduction An overdose of acetaminophen may result in severe liver injury. Acetylcysteine is an effective antidote to prevent or limit liver injury in patients with potentially toxic acetaminophen levels or evidence of liver injury. (acetaminophen) 40 Definitions Overdosage of acetaminophen can occur following an acute overdose or during repeated overdose. Acute acetaminophen overdose is defined as an ingestion of a toxic amount of acetaminophen occurring within a period of 8 hours or less. In adults and adolescents, hepatotoxicity may occur following ingestion of greater than 7.5 to 10 grams (g) (eg, 24 regular-strength or 15 extra-strength caplets or tablets) over a period of 8 hours or less. Fatalities are infrequent especially when treated with acetylcysteine (0.3% of treated cases). A chronic overdose is termed repeated supratherapeutic ingestion (RSTI) to differentiate from chronic therapeutic use. Ingestion of a toxic amount over a period greater than 8 hours is considered a repeated supratherapeutic ingestion. Acetylcysteine is the official term designated by USAN (United States Adopted Names) for N-acetylcysteine. (acetaminophen) 41 Management of Acute Overdose To achieve optimal outcome following acetaminophen overdose, a systematic management approach is needed. This section outlines basic steps in managing acute acetaminophen overdose, consistent with FDA approved labeling of acetylcysteine. Flowchart 1 outlines this stepwise approach. 1. Initial Assessment 2. Gastric Decontamination/Prevention of Absorption Adults or adolescents (*12 years of age) who may have ingested Gastric decontamination should be carried out according to standard acetaminophen in a purposeful overdose, independent of the amount treatment guidelines. Activated charcoal reduces the peak serum con- reported to have been ingested, should be referred for medical evalu- centration of acetaminophen. This may reduce the 4 hour acetaminophen ation. Their evaluation includes careful estimation of the quantity and level and thereby decrease the number of patients requiring treatment dosage form of the acetaminophen ingested as well as assessment of any with acetylcysteine. Activated charcoal may be given during the immedi- other substances ingested. The acetaminophen level should be deter- ate postingestion period, especially in the case of a mixed drug overdose. mined at 4 hours post ingestion or as soon as possible thereafter (see Data supporting the efficacy of activated charcoal beyond 2 hours after also Special Considerations). ingestion are limited. Administration of activated charcoal does not require a change in subsequent administration of oral or intravenous Patients who present with a measurable acetaminophen level and no acetylcysteine therapy. clear time of exposure represent a treatment challenge and there is sub- stantial practice variation. In some cases it is possible to develop a “worst case scenario” for the time of ingestion (e.g. the patient was with their family until 12 hours prior to presentation so ingestion could not have occurred more than 12 hours prior). In these cases, the earliest possible time of ingestion should be used to plot the acetaminophen level on the nomogram (Chart 1). If the time of ingestion is completely unknown, the most conservative approach is to initiate treatment and continue acetyl- cysteine until the acetaminophen level is undetectable and there is no evidence of progressive hepatic injury (serum transaminases normal or near normal and stable over a 12 hour period). There is substantial practice variation in the management of patients who have low level transaminase elevations and a questionable history of the time and amount of acetaminophen exposure. In many of these cases the acetaminophen level may be therapeutic or even undetectable. The most conservative approach in these cases is to initiate treatment and continue acetylcysteine until the acetaminophen level is undetectable and there is no evidence of progressive hepatic injury (serum transaminases normal or near normal and stable over a 12 hour period). (acetaminophen) 42 MANAGEMENT OF ACUTE OVERDOSE 3. Determining the Need for Acetylcysteine 4. Administration of Acetylcysteine Acetaminophen Assay If a patient presents within 4 hours of an acute overdose, treatment with Rationale acetylcysteine should be withheld until acetaminophen assay results are available, provided that initiation of treatment is not delayed beyond 8 The acetaminophen level provides the basis for determining the need to hours following the ingestion. initiate or continue treatment with acetylcysteine. Either the plasma or serum acetaminophen level may be used; most hospitals determine the If a patient with a potential acetaminophen overdose presents for care serum acetaminophen level. The serum acetaminophen level should be more than 8 hours after ingestion, acetylcysteine should be administered measured at 4 hours following ingestion of an acute overdose or as soon immediately, regardless of the quantity of acetaminophen reported to as possible thereafter. It is important to determine the time of ingestion have been ingested. It is important not to wait for results of the acetamin- accurately. If the ingestion occurred
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