What are the liver side effects of Rifampin (Rifampicin)?

From the Guidelines

Rifampin can cause significant liver injury, and patients taking this medication should be closely monitored for signs of liver damage, with baseline liver function tests obtained before starting treatment and follow-up testing recommended at 2-4 week intervals, especially in the first three months of treatment. The risk of liver toxicity increases in patients with pre-existing liver disease, alcohol use disorder, advanced age, or when rifampin is combined with other hepatotoxic medications like isoniazid 1. According to the most recent guidelines, patients with pre-existing liver disease should be frequently monitored for drug-induced liver damage, and rifampin should still be used if possible due to its effectiveness in treating tuberculosis 1.

Monitoring and Management

• Patients taking rifampin should be monitored for signs of liver damage, including elevated liver enzymes, jaundice, dark urine, abdominal pain, nausea, vomiting, and fatigue.
• Baseline liver function tests should be obtained before starting rifampin, with follow-up testing recommended at 2-4 week intervals, especially in the first three months of treatment.
• The mechanism of rifampin-induced liver injury involves both direct hepatotoxicity and immune-mediated hypersensitivity reactions.
• Rifampin also induces cytochrome P450 enzymes, which can affect the metabolism of many drugs and potentially increase liver stress.

Special Considerations

• Patients with pre-existing liver disease are at a higher risk of liver toxicity and should be closely monitored.
• The combination of rifampin with other hepatotoxic medications like isoniazid may increase the risk of liver injury.
• Patients should avoid alcohol while taking rifampin to reduce the risk of liver damage.
• If signs of liver injury develop, rifampin should be promptly discontinued and medical attention sought 1.

From the FDA Drug Label

WARNINGS Hepatotoxicity of hepatocellular, cholestatic, and mixed patterns has been reported in patients treated with rifampin. Severity ranged from asymptomatic elevations in liver enzymes, isolated jaundice/hyperbilirubinemia, symptomatic self-limited hepatitis to fulminant liver failure and death Severe hepatic dysfunction including fatalities were reported in patients with liver disease and in patients taking rifampin with other hepatotoxic agents. Monitor for symptoms and clinical/laboratory signs of liver injury, especially if treatment is prolonged or given with other hepatotoxic drugs Patients with impaired liver function should be given rifampin only in cases of necessity and then under strict medical supervision.

Rifampin Liver Side Effects:

• Hepatotoxicity of hepatocellular, cholestatic, and mixed patterns
• Severity ranges from asymptomatic elevations in liver enzymes to fulminant liver failure and death
• Severe hepatic dysfunction, including fatalities, reported in patients with liver disease and those taking rifampin with other hepatotoxic agents
• Monitor for symptoms and clinical/laboratory signs of liver injury, especially with prolonged treatment or use with other hepatotoxic drugs
• Patients with impaired liver function should only receive rifampin under strict medical supervision 2 2

From the Research

Rifampin Liver Side Effects

• Rifampin is a powerful enzyme inducer that may enhance the hepatotoxicity of isoniazid, although it is rarely or not hepatotoxic on its own 3.
• The risk of hepatotoxicity is increased in patients with liver cirrhosis, and the management of patients with underlying cirrhosis is a challenge 4.
• Rifampin can produce competition for the elimination of bilirubin and bromsulphalein by the liver, which is rapidly reversible when treatment is discontinued 5.
• There is no consistent evidence that giving rifampicin with isoniazid increases the risk of hepatitis, and transient abnormalities in liver function tests during the early weeks of treatment do not imply serious toxicity 6.
• The incidence of hepatotoxicity due to rifampicin, isoniazid, and pyrazinamide was 8.8% in a study of 534 patients, and anti-HIV positive and high doses of isoniazid were considered independent risk factors for hepatotoxicity 7.

Monitoring and Management

• Patients with underlying liver test abnormalities should not be given pyrazinamide, and isoniazid and pyrazinamide should be administered at the lowest dosage within their respective therapeutic ranges 3.
• Serum transaminase levels should be determined twice weekly during the first 2 weeks of treatment, every 2 weeks during the rest of the first 2 months, and every month thereafter 3.
• Therapy with isoniazid, rifampicin, and pyrazinamide should be stopped when serum transaminase levels increase to greater than 3 times the upper limit of normal 3.
• There are no established guidelines for the treatment of TB in relation to the severity of liver disease, and no specific treatment exists for prevention or treatment of hepatotoxicity 4.