How often should liver enzymes, including alanine transaminase (ALT) and aspartate transaminase (AST), be monitored in patients on oral tretinoin?

Liver Enzyme Monitoring for Oral Isotretinoin (Tretinoin)

Check liver enzymes at baseline and at 2 months into treatment, with additional monitoring only as clinically indicated or with dose changes. 1

Recommended Monitoring Schedule

Initial Phase

• Baseline testing: Obtain ALT and AST before starting isotretinoin 1
• Single follow-up at 2 months: Recheck liver enzymes once treatment dose is established 1
• No routine monitoring thereafter: Once stable on dose, routine monitoring is not recommended for otherwise healthy patients 1, 2

Rationale for Reduced Monitoring

The evidence strongly supports less frequent monitoring than historically practiced:

• Low incidence of clinically significant elevations: Most liver enzyme abnormalities during isotretinoin therapy are mild (Grade 1) and do not progress even when the medication is continued 3
• Poor predictive value: Routine complete blood counts are explicitly not recommended, and the same principle applies to excessive liver enzyme monitoring 1
• Most abnormalities occur early: When elevations do occur, 48% happen during the first month of therapy, making the 2-month checkpoint appropriate for detection 3

Management of Elevated Liver Enzymes

Grade 1 Elevations (ALT/AST >ULN to 3× ULN)

• Continue isotretinoin at current dose: Of 122 Grade 1 AST elevations managed by maintaining dose, 40 normalized and only 1 progressed to Grade 2 3
• No additional testing required: Most mild elevations do not worsen and resolve spontaneously 3

Grade 2-3 Elevations (ALT/AST >3× ULN)

• Discontinue isotretinoin temporarily if transaminases exceed 3 times upper normal limit 1
• Institute weekly monitoring until levels normalize 1
• Refer to gastroenterology if bilirubin >50 µmol/L or ALT >200 IU/L 1

Severe Elevations

• Permanent discontinuation may be necessary for persistent severe elevations 1
• ALT normalization timeline: Can take up to 8 months after discontinuation in rare cases, though rechallenge may be successful once normalized 4

Special Populations Requiring More Frequent Monitoring

Monitor more frequently (every 2-4 weeks initially, then every 3 months) in patients with:

• Pre-existing liver disease 1
• Concurrent hepatotoxic medications 1
• History of excess alcohol intake 1
• Dose adjustments or changes 1

Common Pitfalls to Avoid

• Over-monitoring healthy patients: The 2016 AAD guidelines explicitly state routine CBC monitoring is unwarranted, and the same conservative approach applies to liver enzymes in low-risk patients 1
• Discontinuing for mild elevations: Grade 1 elevations rarely progress and typically resolve without intervention 3
• Ignoring lipid monitoring: While liver enzymes require minimal monitoring, triglycerides should be checked at baseline and 2 months, as severe hypertriglyceridemia (>10 mmol/L) poses acute pancreatitis risk 1

Key Distinction from Other Retinoids

Note that the evidence provided includes acitretin monitoring protocols (every 2-4 weeks for 2 months, then every 3 months), but isotretinoin requires less frequent monitoring based on more recent evidence and its different safety profile 1