How to manage elevated Serum Glutamic-Pyruvic Transaminase (SGPT) due to anti-tuberculosis (TB) medications?

Management of Elevated SGPT Due to Anti-TB Medications

When SGPT/ALT levels rise to five times normal or bilirubin rises, immediately stop hepatotoxic drugs (isoniazid, rifampicin, and pyrazinamide). 1, 2

Initial Assessment and Management

• Investigate non-drug etiologies such as viral hepatitis to rule out other causes of liver enzyme elevation 2
• For mild elevations (less than 2 times normal), continue monitoring liver function tests every 2 weeks 2
• For moderate elevations (2-5 times normal), monitor liver function weekly for two weeks, then biweekly until normal 2, 1
• If SGPT/ALT rises to five times normal or bilirubin rises, immediately stop all hepatotoxic drugs (isoniazid, rifampicin, and pyrazinamide) 2, 1
• Continue treatment with less hepatotoxic drugs such as ethambutol, injectable agents (streptomycin), fluoroquinolones, and cycloserine 2, 1

Management Based on Clinical Status

• For non-infectious TB forms in patients who are not acutely ill, no treatment is needed until liver function normalizes 1
• For infectious TB (sputum smear positive) or acutely ill patients, use non-hepatotoxic drugs while waiting for liver function to normalize 1
• Streptomycin and ethambutol are the preferred alternatives with appropriate monitoring 1, 2

Reintroduction Protocol After Liver Function Normalizes

1. Sequential reintroduction of drugs with daily monitoring of clinical condition and liver function 1, 2:

   • Start with isoniazid at 50 mg/day, increasing to 300 mg/day after 2-3 days if no reaction occurs 2, 1
   • After 2-3 days without reaction, add rifampicin at 75 mg/day, increasing to 300 mg after 2-3 days, then to full dose (450-600 mg based on weight) after another 2-3 days 2, 1
   • Finally, add pyrazinamide at 250 mg/day, increasing to 1.0 g after 2-3 days and then to full dose gradually 2, 1

2. If a specific drug is identified as the cause of hepatotoxicity, it should be permanently excluded from the regimen and a suitable alternative used 1

Risk Factors and Monitoring

• Pre-existing liver disease, advanced age, and alcohol consumption increase risk of hepatotoxicity 1, 2
• Regular monitoring of liver function is required for patients with known chronic liver disease (weekly for two weeks, then biweekly for the first two months) 1
• For patients without pre-existing liver disease and normal pre-treatment LFTs, routine monitoring is not required, but LFTs should be repeated if symptoms develop (fever, malaise, vomiting, jaundice, or unexplained deterioration) 1, 2

Common Pitfalls to Avoid

• Failing to recognize early signs of hepatotoxicity (anorexia, nausea, vomiting, fatigue, malaise, and weakness) 3
• Reintroducing drugs too quickly after hepatotoxicity has occurred 2
• Not adjusting treatment regimens for patients with pre-existing liver disease 1
• Overlooking drug interactions that may potentiate hepatotoxicity 2

Alternative Regimens

• If pyrazinamide is found to be the offending drug, treatment will need to be continued for nine months with rifampicin and isoniazid 1
• For severe cases where multiple drugs cannot be tolerated, consult with a TB specialist for individualized regimens 4

Remember that drug-induced hepatotoxicity can be life-threatening, and prompt recognition and management are essential for preventing morbidity and mortality in TB patients.