From the FDA Drug Label
If abnormalities of liver function exceed three to five times the upper limit of normal, discontinuation of isoniazid should be strongly considered The FDA drug label recommends holding Tuberculosis treatment with RIPE therapy, which includes Isoniazid, when liver function tests (LFTs) exceed three to five times the upper limit of normal 1.
- Key consideration: Discontinuation of Isoniazid should be strongly considered at this level of elevated LFTs.
- Clinical decision: Hold RIPE therapy when LFTs exceed three to five times the upper limit of normal.
From the Research
Tuberculosis treatment with RIPE therapy should be held when liver function tests (LFTs) exceed 5 times the upper limit of normal (ULN) regardless of symptoms, as this approach prioritizes the prevention of severe hepatitis, liver failure, and potentially death, which outweighs the risk of briefly interrupting TB treatment. This recommendation is based on the most recent and highest quality study available, which highlights the importance of monitoring LFTs during TB treatment, especially in patients with underlying liver disease 2.
Key Considerations
- Symptoms of hepatitis, such as nausea, vomiting, abdominal pain, jaundice, and fatigue, should be closely monitored, and if present with LFT elevations above 3 times the ULN, treatment should be held.
- The hepatotoxicity of TB medications, particularly Rifampicin, Isoniazid, and Pyrazinamide, necessitates careful management and monitoring of LFTs during treatment.
- Ethambutol is not significantly hepatotoxic and can generally be continued, but close monitoring of LFTs is still essential.
Management Approach
- If a patient develops concerning LFT elevations, all hepatotoxic medications should be immediately discontinued.
- Once LFTs return to normal or near baseline levels, medications can be reintroduced sequentially, typically starting with Rifampicin, followed by Isoniazid, and then Pyrazinamide if necessary, with close monitoring of LFTs.
- This approach is supported by studies that demonstrate the feasibility of continuing or reintroducing TB treatment in patients with elevated LFTs, provided that close monitoring and appropriate management are in place 3, 2.
Prioritizing Patient Safety
- The risk of severe hepatitis, liver failure, and potentially death associated with continued TB treatment in the face of significant LFT elevations outweighs the risk of briefly interrupting treatment.
- Therefore, a cautious approach that prioritizes patient safety and monitors LFTs closely is essential in the management of TB treatment with RIPE therapy.