What alternative analgesics are available for a patient with elevated liver enzymes due to alcohol use and concomitant naltrexone (Naltrexone) therapy, who is experiencing severe knee pain and requires a stronger medication than acetaminophen (Tylenol)?

From the Guidelines

For a patient with elevated liver enzymes due to alcohol use and naltrexone therapy who needs stronger pain management than Tylenol for severe knee pain, I recommend considering tramadol as a first-line option, as conditionally recommended by the 2019 American College of Rheumatology guideline 1. Tramadol can be started at 50mg every 6 hours as needed, with a maximum daily dose of 400mg. Unlike traditional opioids, tramadol has a dual mechanism of action (weak mu-opioid receptor binding and serotonin/norepinephrine reuptake inhibition) and may cause less respiratory depression. Some key points to consider when managing knee pain in this patient include:

• Avoiding traditional NSAIDs (ibuprofen, naproxen) as they can worsen liver function, as noted in the 2012 American College of Rheumatology recommendations 1
• Limiting acetaminophen doses to less than 2g daily if used at all, as recommended by the 2012 American College of Rheumatology guidelines 1
• Considering topical NSAIDs like diclofenac gel 1% applied to the knee four times daily, which can provide localized pain relief without significant systemic absorption that would impact the liver
• Incorporating non-pharmacological approaches, including physical therapy, knee bracing, ice/heat therapy, and weight management if appropriate
• Regular liver function monitoring is essential while on any medication, and the patient should completely avoid alcohol to prevent further liver damage and reduce drug interactions. It's also important to note that the 2019 American College of Rheumatology guideline conditionally recommends against the use of non-tramadol opioids, colchicine, fish oil, vitamin D, bisphosphonates, and glucosamine for knee OA management 1.

From the FDA Drug Label

Hepatic Effects Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including naproxen Hepatic abnormalities may be the result of hypersensitivity rather than direct toxicity. These laboratory abnormalities may progress, may remain essentially unchanged, or may be transient with continued therapy. The SGPT (ALT) test is probably the most sensitive indicator of liver dysfunction Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of more severe hepatic reaction while on therapy with naproxen. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (eg, eosinophilia, rash, etc.), naproxen should be discontinued. Chronic alcoholic liver disease and probably other diseases with decreased or abnormal plasma proteins (albumin) reduce the total plasma concentration of naproxen, but the plasma concentration of unbound naproxen is increased. Caution is advised when high doses are required and some adjustment of dosage may be required in these patients It is prudent to use the lowest effective dose.

The patient has elevated liver enzymes from alcohol use and is on naltrexone, and needs a stronger medication than Tylenol for severe knee pain.

• Naproxen is an option, but caution is advised due to the patient's liver condition.
• The patient should be evaluated for evidence of the development of more severe hepatic reaction while on therapy with naproxen.
• Dosage adjustment may be required due to the patient's chronic alcoholic liver disease.
• It is prudent to use the lowest effective dose of naproxen.
• The patient should be monitored closely for any signs of liver dysfunction or other adverse effects. 2

From the Research

Patient's Condition

The patient has elevated liver enzymes due to alcohol use and is currently on naltrexone. The patient is also experiencing severe knee pain and requires a stronger medication than Tylenol.

Available Options

• The patient's liver enzyme elevation is likely due to alcohol use and naltrexone therapy, as supported by studies 3, 4.
• Naltrexone has been shown to be safe for patients with underlying liver disease, including those with compensated cirrhosis 4.
• Low-dose naltrexone has been used to treat chronic pain conditions, including fibromyalgia and inflammatory bowel conditions 5.
• High-dose naltrexone has been studied for its safety in terms of liver function, with no adverse clinical or laboratory changes observed in one study 6.
• Abnormal liver enzymes can be categorized based on the pattern and magnitude of aminotransferase elevation, and can be caused by various factors including alcohol use, medication-induced liver injury, and chronic viral hepatitis 7.

Considerations for Pain Management

• The patient's severe knee pain requires a stronger medication than Tylenol, but the choice of medication should take into account the patient's elevated liver enzymes and naltrexone therapy.
• Alternative pain management options may include non-steroidal anti-inflammatory drugs (NSAIDs) or opioids, but these should be used with caution and under close monitoring due to the patient's liver disease and naltrexone therapy.
• Low-dose naltrexone may be considered as an adjunctive therapy for chronic pain management, as it has been shown to be effective in reducing symptoms related to chronic pain conditions 5.