From the Guidelines
You should stop both Febuxostat and HRZE (isoniazid, rifampicin, pyrazinamide, and ethambutol) if you have elevated liver enzymes, and contact your healthcare provider immediately. These medications are known to cause liver toxicity, with HRZE being particularly hepatotoxic, as noted in studies such as 1 and 1. When liver enzymes become elevated, this indicates potential liver damage that could worsen if the medications are continued. Your doctor will likely recommend temporarily discontinuing these drugs until your liver enzymes return to normal levels. They may monitor your liver function with blood tests (ALT, AST, bilirubin) and then potentially restart the medications at lower doses or modify your treatment regimen. For tuberculosis treatment with HRZE, your doctor might adjust the regimen by removing the most hepatotoxic components (usually pyrazinamide first) while maintaining effective TB treatment, as suggested in 1. For gout management, alternative medications to Febuxostat might be considered. Never stop these medications without medical supervision, as abrupt discontinuation of TB treatment can lead to drug resistance. Some key points to consider include:
- Monitoring liver function regularly, especially in patients with pre-existing liver disease, as recommended in 1.
- Being aware of the signs of hepatotoxicity, such as vomiting, malaise, and jaundice, and seeking medical attention immediately if they occur, as advised in 1.
- Considering alternative treatments for gout and tuberculosis that may be less hepatotoxic, as discussed in 1 and 1. It's essential to follow the guidance of your healthcare provider and not to stop any medication without their supervision to ensure the best outcome for your health.
From the Research
Elevated Liver Enzymes and Medication
- SGPT (alanine aminotransferase) levels above 200 can be a cause for concern, as they may indicate liver damage or injury 2.
- In cases of elevated liver enzymes, it is essential to assess the degree of elevation and guide the evaluation accordingly 2.
- The evaluation of hepatocellular injury, which is defined as disproportionate elevation of AST and ALT levels compared with alkaline phosphatase levels, includes testing for viral hepatitis, nonalcoholic fatty liver disease, and screening for hereditary hemochromatosis, among others 2.
Febuxostat and HRZE Tablets
- Febuxostat is a medication used to treat gout, while HRZE (isoniazid, rifampicin, pyrazinamide, and ethambutol) is a combination of antibiotics used to treat tuberculosis.
- There is no direct evidence in the provided studies that suggests Febuxostat and HRZE tablets should be stopped immediately in cases of elevated liver enzymes.
- However, it is crucial to monitor liver function tests and adjust medication accordingly, as some medications, including antibiotics like HRZE, can cause liver injury 3, 4.
- A study on the bioequivalence of rifampicin, isoniazid, and pyrazinamide in a fixed-dose combination found that the FDC tablet was bioequivalent to separate formulations at the same dose levels 5.
- Another study on the efficacy and safety of combined isoniazid-rifampicin-pyrazinamide-levofloxacin dry powder inhaler in treatment of pulmonary tuberculosis found that add-on DPI therapy was safe, but did not increase MTB sputum culture conversion at two months of treatment 6.
Considerations for Discontinuation of Medication
- Clinically significant drug-induced liver injury (DILI) is defined by elevations of alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN), alkaline phosphatase (ALP) ≥2 × ULN, or ALT ≥3 × ULN and total bilirubin TBIL >2 × ULN 3.
- In cases where DILI is suspected, discontinuation of the causative drug and/or close monitoring of the patient may be necessary 3.
- It is essential to consult with a healthcare professional to determine the best course of action for managing elevated liver enzymes and medication use.