51: Acetaminophen Overdose

INTRODUCTION AND BACKGROUND

Acetaminophen is the most widely used analgesic and a commonly used antipyretic. It has been available as an over-the-counter formulation for more than 50 years and is exceptionally safe when used according to manufacturer directions.¹ Unfortunately, toxic levels can make it a silent and lethal killer because overdose may initially present with few, if any, symptoms.^2–5 If not promptly discovered and treated, acetaminophen toxicity can lead to liver failure and death unless a successful liver transplant is performed.^5–11

Acetaminophen is packaged under multiple names and is a component of many different medicinal products around the globe. In the United States it is commonly sold as the brand name Tylenol®, whereas in the United Kingdom it is generally sold under the alternate generic names of paracetamol and N-acetyl-p-aminophenol (APAP).¹²

In the United States, acetaminophen is available in varied doses and forms. Oral dosage formulations include 325 and 500 mg immediate-release as well as 650 mg extended-release products. For all formulations, the adult dose should not exceed 1,000 mg for a single dose or 4,000 mg per day.¹³ Pediatric acetaminophen products are also available in multiple formulations, including concentrated drops, liquid suspensions, suppositories, chewable tablets, and orally disintegrating tablets.^12,13 Pediatric doses should not exceed 15 mg/kg per single dose (up to a maximum of 1,000 mg per dose) or 75 mg/kg/day (up to a maximum of 4,000 mg per day).^12,14,15

Acetaminophen is found in many over-the-counter and prescription medicines such as Sudafed PE® Severe Cold (acetaminophen, diphenhydramine, and phenylephrine), Percocet® (acetaminophen and oxycodone), and Fioricet® (acetaminophen, butalbital, and caffeine). Unintentional overdose may occur with these combination products because the general public is unaware of the specific medications in such formulations and may inadvertently exceed the maximum single or daily acetaminophen dosage when taking multiple combination products simultaneously.

In an effort to reduce unintentional acetaminophen overdose, the U.S. Food and Drug Administration (FDA) requested that manufacturers limit the strength of acetaminophen in all prescription drug products to 325 mg by January 2014.¹⁶ The FDA subsequently announced in March 2014 that all prescription drug products containing acetaminophen in the U.S. market have been successfully limited to 325 mg per dose unit. These formulation changes do not apply to over-the-counter (OTC) acetaminophen products.

Acetaminophen overdose may be acute or chronic (Figure 51-1). An acute overdose is generally defined as a toxic dose (>150 mg/kg or >7.5 g) ingested in <8 hours. A chronic overdose is also referred to as “repeated supratherapeutic ingestion” and is generally defined as a toxic dose taken over >8 hours.^17,18 Overdose may be accidental, as is frequently the case with pediatric overdoses, or intentional, as is the case with suicide attempts.