What is the management for a patient taking isotretinoin (13-cis-retinoic acid) with elevated Liver Function Tests (LFTs) 2-3 times the normal range?

From the Guidelines

For a patient taking isotretinoin with LFTs elevated 2-3 times the normal range, the recommended management is to continue monitoring while maintaining the current isotretinoin dose in most cases, as supported by the most recent guidelines 1. The management of elevated Liver Function Tests (LFTs) in patients taking isotretinoin involves careful consideration of the potential risks and benefits of continuing therapy.

Key Considerations

• The patient's LFTs are elevated 2-3 times the normal range, which is a common side effect of isotretinoin therapy 1.
• The mechanism of isotretinoin's effect on liver enzymes involves altered lipid metabolism and potential direct hepatocyte effects.
• Isotretinoin-induced LFT elevations are usually transient and asymptomatic, with most resolving spontaneously without intervention.

Recommended Management

• Continue monitoring LFTs monthly while maintaining the current isotretinoin dose in most cases 1.
• Temporary dose reduction may be considered if levels are persistently elevated or approaching 3 times normal.
• Complete discontinuation is typically only necessary if LFTs exceed 3 times normal or if symptoms of hepatotoxicity develop (jaundice, abdominal pain, fatigue).
• Alcohol should be avoided during treatment as it may exacerbate liver stress.
• If LFTs continue to rise despite dose adjustment or if the patient develops symptoms, consultation with a dermatologist and possibly a hepatologist is warranted to determine the appropriate course of action.

Additional Considerations

• Population-based studies have not identified increased risk of neuropsychiatric conditions or inflammatory bowel disease with isotretinoin 1.
• For persons of pregnancy potential, pregnancy prevention is mandatory, and daily dosing over intermittent dosing is recommended 1.

From the FDA Drug Label

Since elevations of liver enzymes have been observed during clinical trials, and hepatitis has been reported, pretreatment and follow-up liver function tests should be performed at weekly or biweekly intervals until the response to isotretinoin has been established (see WARNINGS, Hepatotoxicity)

The management for a patient taking isotretinoin with elevated Liver Function Tests (LFTs) 2-3 times the normal range is to monitor LFTs at weekly or biweekly intervals.

• Pretreatment and follow-up liver function tests are recommended to establish the response to isotretinoin.
• The patient should be closely monitored for signs of hepatotoxicity.
• No specific guidance is provided in the drug label for managing elevated LFTs in patients taking isotretinoin, therefore, management should be individualized and based on clinical judgment 2.

From the Research

Management of Elevated LFTs in Patients Taking Isotretinoin

• The management of patients taking isotretinoin with elevated Liver Function Tests (LFTs) 2-3 times the normal range involves careful monitoring and consideration of potential causes, including the medication itself and other factors such as dietary supplements 3.
• A study published in 2021 found that most mild elevations of liver enzymes in patients taking isotretinoin do not worsen, and that acne patients with isotretinoin may not need continued testing when experiencing low-grade liver enzyme abnormalities 4.
• However, another study published in 2017 found that dietary supplementation, including protein and herbal supplements, may cause liver function abnormalities in patients taking isotretinoin, and that clinicians should consider counseling their patients to avoid these products 3.
• A survey of dermatologists published in 2017 found that 75% of respondents would stop isotretinoin when AST or ALT values reach 3 times normal, and 89% would stop at 4 times normal 5.
• The potential hepatotoxic effects of isotretinoin are also supported by a study published in 2022, which found that isotretinoin induced hepatotoxicity in rats, but that administration of taurine prevented this toxicity 6.

Monitoring and Treatment

• Regular monitoring of LFTs is recommended for patients taking isotretinoin, with the frequency and type of tests varying depending on the patient's individual risk factors and the dermatologist's preference 5.
• If LFTs are elevated 2-3 times the normal range, the patient's treatment plan may need to be adjusted, including potentially stopping the medication or reducing the dose 5.
• Patients should also be counseled on the potential risks of dietary supplements and the importance of avoiding these products while taking isotretinoin 3.