Can Fioricet (Butalbital, Acetaminophen, and Caffeine) cause elevated liver enzymes, specifically hepatocellular injury or hepatitis?

From the Guidelines

Fioricet can cause elevated liver enzymes, particularly with excessive use or in people with pre-existing liver conditions, due to its acetaminophen component. Fioricet contains acetaminophen (typically 325mg per tablet), butalbital (a barbiturate, 50mg), and caffeine (40mg). The acetaminophen component is primarily responsible for potential liver damage when taken in high doses or for prolonged periods, as seen in cases of acetaminophen hepatotoxicity 1. According to the most recent guidelines, discontinuation of the causal agent is the only effective treatment in most idiosyncratic DILI cases, and delayed discontinuation can result in irreversible liver failure and death 1.

Some key points to consider:

• The recommended maximum daily dose of acetaminophen is 3,000-4,000mg (equivalent to 9-12 Fioricet tablets), but taking even less can cause problems in some individuals.
• Signs of liver issues include yellowing of skin or eyes, dark urine, upper right abdominal pain, or unusual fatigue.
• People with liver disease, alcohol use disorder, or who take other acetaminophen-containing medications are at higher risk.
• Regular liver function tests are advisable for those using Fioricet long-term.
• The liver damage occurs because acetaminophen is metabolized into a toxic compound (NAPQI) that can harm liver cells when produced in excessive amounts that overwhelm the liver's protective mechanisms.

It is essential to monitor liver enzymes and consider discontinuation of Fioricet if liver damage is suspected, following the guidelines for detection, assessment, and management of suspected acute drug-induced liver injury 1. The most critical consideration is to prioritize the patient's liver health and take prompt action if liver enzymes become elevated, as delayed discontinuation can have severe consequences.

From the FDA Drug Label

WARNINGS Liver warning: This product contains acetaminophen. Severe Liver damage may occur if you take Ask a doctor before use if you have liver disease.

• Liver Damage: The FDA drug label warns of severe liver damage associated with acetaminophen, which is an ingredient in Fioricet.
• Elevated Liver Enzymes: While the label does not directly mention elevated liver enzymes, severe liver damage can be associated with elevated liver enzymes.
• Caution: Given the warning of severe liver damage, it is reasonable to conclude that Fioricet may cause elevated liver enzymes, especially if taken in excess or with other drugs containing acetaminophen, or with excessive alcohol consumption 2, or in patients with pre-existing liver disease 2.

From the Research

Fioricet and Liver Enzymes

• Fioricet is a medication that contains acetaminophen, butalbital, and caffeine.
• The relationship between acetaminophen and liver enzyme elevation has been studied in various research papers 3, 4, 5, 6.
• According to a study published in the American Journal of Therapeutics, acetaminophen can be used safely in patients with liver disease at recommended doses 3.
• However, another study found that patients with underlying liver disease are at higher risk of poor outcomes from acetaminophen overdose 4.
• A case report published in the American Journal of Therapeutics described a patient who experienced moderate liver enzyme elevation after an acute acetaminophen overdose, despite having an initial undetectable acetaminophen level and normal liver enzymes 6.
• A study published in Clinical Therapeutics found that serious liver disease before administration is an independent risk factor for acetaminophen-induced liver injury 5.

Risk Factors for Liver Injury

• Age ≥70 years and serious liver disease are significant risk factors for acetaminophen-induced liver injury 5.
• High-dose acetaminophen may cause liver injury, and the risk of liver injury increases with higher doses 5.
• Patients with liver disease may be at higher risk of liver injury from acetaminophen due to altered metabolism and depleted glutathione stores 3.

Fioricet-Specific Risks

• There is limited research specifically on the risk of liver enzyme elevation with Fioricet use.
• However, a case report published in Case Reports in Medicine described a patient who developed posterior reversible encephalopathy syndrome (PRES) after taking Fioricet, but did not mention liver enzyme elevation 7.