From the Guidelines
Taking an extra acetaminophen (APAP) on top of a hydrocodone and acetaminophen mixture can lead to excess acetaminophen dosing, which increases the risk of severe liver injury and potentially liver failure or death 1.
Key Points to Consider
- The FDA recommends limiting daily acetaminophen intake to a maximum of 4 g and imposes a limit of 325 mg of acetaminophen per tablet, capsule, or other dosage unit in prescription products to reduce the risk of severe liver injury from acetaminophen overdosing 1.
- The NCCN panel suggests that providers consider limiting chronic administration of acetaminophen to 3 g or less per day due to concerns of hepatic toxicity 1.
- Patients should be advised of the risks of taking additional over-the-counter products containing acetaminophen when formulations are prescribed that combine opioids with acetaminophen 1.
Recommendations for Safe Use
- Clinicians should prescribe immediate-release opioids at the lowest effective dose and for no longer than the expected duration of pain severe enough to require opioids to minimize unintentional initiation of long-term opioid use 1.
- Patients should be educated on the risks of acetaminophen overdose and the importance of not exceeding the recommended daily dose of acetaminophen 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Acetaminophen Overdose and Hepatotoxicity
- Acetaminophen (APAP) overdose is a common cause of serious, often lethal, drug-induced hepatotoxicity 2
- The risk of hepatotoxicity increases with doses above 12g in adults 3
- Taking an extra APAP on top of a hydrocodone and APAP mixture can increase the risk of hepatotoxicity, as APAP is the primary cause of liver damage in these cases 4, 2
Treatment and Prevention of Hepatotoxicity
- N-acetylcysteine (NAC) is an effective treatment for APAP overdose, and can prevent hepatotoxicity when administered within 8 hours of ingestion 5, 3, 6
- NAC works by maintaining intracellular glutathione stores, which helps to detoxify the electrophilic APAP metabolite, NAPQI 3
- Standard dosing of NAC (300mg/kg over 21h) may not be adequate to prevent hepatotoxicity in cases of massive APAP overdose, and additional data is needed to determine the clinical outcomes of these cases 6
Clinical Outcomes of APAP Overdose
- Patients who ingest massive amounts of APAP are at higher risk of developing hepatotoxicity, even with standard NAC treatment 6
- Delayed administration of NAC (after 8h) increases the risk of hepatotoxicity, highlighting the importance of prompt treatment 6
- The clinical outcome of APAP overdose can vary depending on the dose, timing of ingestion, and treatment received, and patients who develop hepatotoxicity may require orthotopic liver transplantation 3