What over‑the‑counter cold medications are safe for an adult with an acute upper‑respiratory infection and elevated liver enzymes?

Cold Medication Safety in Patients with Elevated Liver Enzymes

For an adult with an acute upper respiratory infection and elevated liver enzymes, avoid acetaminophen entirely and use supportive care measures such as decongestants and antihistamines, while immediately stopping all unnecessary medications and investigating the underlying cause of the liver enzyme elevation.

Immediate Actions Required

Stop all unnecessary medications and any known hepatotoxic drugs immediately when liver enzymes are elevated, particularly if AST/ALT exceeds 3× the upper limit of normal. 1 This is the single most important step before considering any cold medication.

• Investigate the underlying cause of elevated liver enzymes before attributing them to any single etiology, including screening for viral hepatitis (A, B, C, E), alcohol use, medication-induced injury, and other competing causes. 2, 1
• Monitor liver function tests closely—twice weekly in patients on potentially hepatotoxic medications or with pre-existing liver disease. 2

Acetaminophen: The Critical Decision

Acetaminophen should be avoided or strictly minimized in patients with elevated liver enzymes, despite being the most common over-the-counter cold medication. 1, 3

• Acetaminophen is the most common cause of drug-induced acute liver failure, accounting for 15% of all acute liver failure cases and up to 50% of fulminant hepatic failure. 1, 3
• The Infectious Diseases Society of America specifically recommends avoiding acetaminophen during acute hepatitis until resolution of the acute episode. 1
• While one older research study suggested acetaminophen could be used safely at recommended doses in stable chronic liver disease 4, this does not apply to patients with acute elevations of liver enzymes where the etiology is unknown.
• Patients must be instructed to stop medication immediately if abdominal pain, vomiting, jaundice, or hepatitis symptoms develop. 3

NSAIDs: Also Contraindicated

NSAIDs (ibuprofen, naproxen) should be avoided in patients with elevated liver enzymes due to hepatotoxicity risk. 1

• NSAIDs carry additional risks of gastrointestinal toxicity, platelet impairment, and nephrotoxicity that make them particularly unsuitable in this population. 4

Safe Symptomatic Treatment Options

Decongestants and antihistamines are the preferred options for symptomatic relief of upper respiratory infections in patients with elevated liver enzymes:

• Pseudoephedrine or phenylephrine for nasal congestion (no specific hepatotoxicity concerns documented in guidelines)
• First-generation antihistamines (diphenhydramine, chlorpheniramine) for rhinorrhea and sneezing
• Saline nasal irrigation and humidified air for supportive care 5

These medications treat the primary symptoms of upper respiratory infections—nasal obstruction, rhinorrhea, and congestion—without the hepatotoxic risk of acetaminophen or NSAIDs. 5, 6

Grading System for Management Decisions

The severity of liver enzyme elevation determines the urgency of medication avoidance:

• Grade 1 (AST/ALT 1-3× ULN): Review and stop unnecessary medications; close monitoring with labs 1-2 times weekly. 1
• Grade 2 or higher (AST/ALT >3× ULN): Stop all unnecessary medications and any known hepatotoxic drugs immediately; temporarily hold other potentially hepatotoxic agents. 1
• Any elevation with symptoms (abdominal pain, jaundice, vomiting): Treat as Grade 2 or higher regardless of laboratory values. 1, 3

Critical Pitfalls to Avoid

Do not rely solely on laboratory values—serum liver tests may not be abnormal in all instances of hepatotoxicity, and clinical symptoms must guide management. 1, 3

• Do not assume the cold infection is causing the liver enzyme elevation without ruling out viral hepatitis, alcohol use, biliary obstruction, and medication-induced injury. 2, 1
• Do not use combination cold medications that contain acetaminophen (many over-the-counter products combine acetaminophen with decongestants). 3
• Advise against alcohol consumption and potentially hepatotoxic dietary supplements during this period. 1

Monitoring Protocol

• Check liver function tests at baseline and monitor according to the severity of elevation (weekly for Grade 1, more frequently for Grade 2 or higher). 2, 1
• Educate patients about symptoms of hepatotoxicity and instruct them to seek immediate medical attention if these develop. 3
• Document all current medications to identify potential drug-drug interactions and hepatotoxic agents. 3