What is the relationship between Minocycline (Minocycline hydrochloride) and Liver Function Tests (LFTs)?

From the Guidelines

Minocycline should be used with caution in patients with liver disease, and monitoring of liver function tests (LFTs) is recommended before starting therapy and periodically during treatment. According to the guidelines on the management of abnormal liver blood tests 1, minocycline is one of the drugs most commonly implicated in liver disease, and its use requires careful monitoring of LFTs. The guidelines recommend that LFTs be monitored before starting minocycline therapy and periodically during treatment, particularly for long-term use.

Key Considerations

• Baseline LFTs should be obtained prior to initiating therapy, with follow-up testing at 1 month, 3 months, and then every 3-6 months for patients on extended courses.
• Minocycline can cause drug-induced liver injury, which typically presents as elevated transaminases (ALT, AST) 1.
• If a patient develops LFT elevations greater than 3 times the upper limit of normal, or if symptoms of liver dysfunction occur (jaundice, abdominal pain, fatigue), minocycline should be discontinued immediately.
• The liver effects are thought to be due to either direct hepatotoxicity or an autoimmune-mediated reaction, and minocycline-induced liver injury is usually reversible upon discontinuation of the medication 1.

Patient-Specific Considerations

• Patients with pre-existing liver disease should use minocycline with caution, and alternative antibiotics should be considered when appropriate.
• The typical dosage of minocycline for most infections is 100 mg twice daily, but this may need adjustment in patients with liver impairment 1.
• Minocycline is contraindicated in patients with hypersensitivity to minocycline, any tetracycline, or any component in the preparation, and its use should be avoided in children under 8 years of age unless benefits outweigh the risks 1.

From the FDA Drug Label

Hepatotoxicity has been reported with minocycline; therefore, minocycline should be used with caution in patients with hepatic dysfunction and in conjunction with other hepatotoxic drugs. Periodic laboratory evaluation of organ systems, including hematopoietic, renal, and hepatic studies should be performed.

Minocycline and LFTs: Minocycline can cause hepatotoxicity, and patients with hepatic dysfunction should be treated with caution.

• Key points:
  • Hepatotoxicity has been reported with minocycline.
  • Use minocycline with caution in patients with hepatic dysfunction.
  • Monitor LFTs (liver function tests) as part of periodic laboratory evaluation of organ systems. 2

From the Research

Minocycline and Liver Function Tests (LFTs)

• Minocycline is an antibacterial drug used in the treatment of acne, and it has been associated with severe adverse reactions, including hepatitis 3.
• A systematic review of the literature found 65 reported cases of hepatitis or liver damage in association with minocycline, with 58% of cases occurring in females and 94% in individuals under 40 years old 3.
• The review identified two types of hepatic reactions: autoimmune hepatitis associated with lupus-like symptoms, and hypersensitivity reaction associated with eosinophilia and exfoliative dermatitis 3.

Risk of Liver Damage

• The risk of liver damage associated with minocycline appears to be small, with an incidence of 1.04 cases/10,000 exposed person months (EPM) compared to 0.69 cases/10,000 EPM for oxytetracycline/tetracycline 4.
• A case-control study found that the adjusted odds ratio (ORadj) of liver dysfunction associated with exposure to minocycline was 2.10 (CI95: 1.30,3.40) compared to nonuse 4.
• A study found that individuals who are HLA-B∗35:02 carriers are at increased risk of developing minocycline-related liver injury, with a 16% carrier frequency in DILI cases compared to 0.6% in population controls 5.

Clinical Characterization

• Minocycline hepatotoxicity can present with prominent autoimmune features in previously healthy individuals, with a median latency from drug start to DILI onset of 318 days 5.
• At presentation, 76% of patients had acute hepatocellular liver injury, with median ALT 1,077 U/L and median bilirubin 4.5 mg/dl 5.
• During follow-up, 50% of patients were treated with corticosteroids, and no participants died or required a liver transplant 5.

Comparison with Other Antibiotics

• Doxycycline is an extremely rare cause of drug-induced liver injury, with a short latency period 6.
• A case report found that a patient developed nausea, vomiting, fatigue, and significant transaminitis consistent with a hepatocellular pattern of liver injury after five days of doxycycline therapy 6.
• The patient recovered completely with the cessation of doxycycline, highlighting the importance of early recognition and discontinuation of the antibiotic in cases of suspected liver injury 6.