From the Guidelines
The incidence of hepatic dysfunction after minocycline use is estimated to occur in approximately 2-17% of patients, with the majority of cases presenting as autoimmune hepatitis (AIH)-like drug-induced liver injury (DILI) [ 1 ].
Key Characteristics of Minocycline-Induced Hepatic Dysfunction
- The latency period of AIH-like DILI varies greatly, ranging from 1–8 weeks to 3–12 months after drug exposure [ 1 ]
- Daily dose: A daily dose of minocycline has been implicated in the development of liver injury, characterized by elevated liver enzymes and, in severe cases, liver failure
- Demographics: The risk of hepatic derangement is estimated to be higher in females, with women being affected 3 to 4 times more frequently than men [ 1 ]
- Clinical manifestations: Cardinal symptoms include nausea, vomiting, lethargy, and right upper quadrant pain, with acute hepatitis being the common manifestation of DILI in more than 60% of all cases [ 1 ]
Diagnosis and Differentiation
- A liver biopsy can be performed to differentiate between DILI and AIH, although DILI may be difficult to distinguish from AIH due to the manifestation of interface hepatitis and plasma cell infiltration [ 1 ]
- The assessment of response to and recurrence after glucocorticoid therapy is helpful in differentiating between AIH and DILI [ 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.
The incidence of hepatic dysfunction after minocycline use is not explicitly stated in the drug label. 2
From the Research
Incidence of Hepatic Dysfunction after Minocycline Use
- The incidence of liver dysfunction in new users of minocycline was 1.04 cases/10,000 exposed person months (EPM) 3.
- A study found that the risk of liver damage associated with minocycline was very small, with an adjusted odds ratio (ORadj) of 2.10 (CI95: 1.30,3.40) compared to nonuse 3.
- Another study reported that 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 4.
- A case report described a 39-year-old woman who developed acute hepatic failure 4 weeks after initiation of oral minocycline, with characteristic features including rash, fever, lymphadenopathy, and eosinophilia 5.
Risk Factors and Characteristics
- A study identified HLA-B∗35:02 as a risk factor for minocycline DILI, with a 16% carrier frequency in DILI cases compared to 0.6% in population controls (odds ratio: 29.6,95% CI: 7.8-89.8, p=2.5×10-8) 4.
- The pattern of distribution in relation to exposure demonstrated two groups: a hypersensitivity reaction occurring within a few weeks of commencing therapy, and an autoimmune hepatitis usually presenting after exposure to minocycline of a year or more, which is more common in women and sometimes associated with lupus-like symptoms 6.
- A real-world data study found that the incidence rate of severe acute liver injury after minocycline initiation was 0 events per 10,000 person-years 7.
Clinical Presentation and Outcomes
- Minocycline-induced hepatic injury is an idiosyncratic reaction with a sensitization period that appears to be 3-4 weeks in duration 5.
- The characteristic features of minocycline-induced hepatic injury include rash, fever, lymphadenopathy, and eosinophilia, as well as severe alterations in liver function 5.
- A study reported that 50% of patients with minocycline DILI were treated with corticosteroids, and no participants died or required a liver transplant 4.