Can I start levofloxacin and ethambutol (antitubercular medications) in a patient with tuberculosis (TB) and impaired liver function (hepatotoxicity)?

Using Levofloxacin and Ethambutol in TB Patients with Hepatotoxicity

Levofloxacin and ethambutol are safe and recommended options for treating tuberculosis in patients with impaired liver function or hepatotoxicity. 1

Safety Profile in Hepatic Impairment

Ethambutol

• Ethambutol is a first-line drug for treating all forms of tuberculosis that is primarily cleared by the kidneys, not the liver 1
• Unlike isoniazid, rifampin, and pyrazinamide, ethambutol is rarely or not hepatotoxic 2
• Can be safely used in patients with underlying liver disease with appropriate monitoring 1

Levofloxacin

• Levofloxacin pharmacokinetics are not expected to be affected by hepatic impairment due to its limited metabolism by the liver 3
• The FDA label states: "Due to the limited extent of levofloxacin metabolism, the pharmacokinetics of levofloxacin are not expected to be affected by hepatic impairment" 3
• Clinical studies have demonstrated that fluoroquinolones cause no additional hepatotoxicity when used in patients with hepatitis induced by first-line anti-TB drugs 4

Treatment Algorithm for TB with Hepatotoxicity

1. Stop hepatotoxic drugs (isoniazid, rifampin, pyrazinamide) when:

   • Clinical suspicion of hepatitis (vomiting, abdominal pain, jaundice) 1
   • AST/ALT > 3 times upper limit of normal with symptoms 4
   • AST/ALT > 5 times upper limit of normal regardless of symptoms 4

2. Continue treatment with less hepatotoxic medications:

   • Ethambutol
   • Fluoroquinolones (levofloxacin)
   • Injectable agents (if needed) 1

3. Monitor liver function:

   • Regular liver chemistry monitoring should be performed 1
   • Monitor for clinical signs of hepatitis 3

Evidence Supporting This Approach

The European Respiratory Society/American Thoracic Society guidelines specifically recommend: "In cases of non-severe tuberculosis, treatment should include isoniazid and ethambutol avoiding rifamycins. Levofloxacin can replace isoniazid if its use is not possible." 1

A clinical study by Yew et al. (2009) demonstrated that levofloxacin and moxifloxacin caused no additional hepatotoxicity when used in patients with hepatitis induced by first-line anti-TB drugs 4. The time to liver function normalization was similar between patients receiving ethambutol alone and those receiving ethambutol plus levofloxacin.

Potential Side Effects to Monitor

Ethambutol

• Retrobulbar neuritis (dose-related, minimal risk at 15 mg/kg daily) 1
• Monitor visual acuity and color discrimination 1
• Any deterioration in visual fields or color vision should lead to stopping ethambutol 1

Levofloxacin

• Tendinitis or tendon rupture (especially in elderly or those on corticosteroids) 3
• Neurologic effects (dizziness, insomnia, tremulousness, headache) 3
• QT interval prolongation (monitor in patients with risk factors) 3

Special Considerations

1. Dosing adjustments:

   • Ethambutol: Standard dose (15-20 mg/kg daily) can be used in hepatic impairment 1
   • Levofloxacin: No dosage adjustment needed for hepatic impairment 3

2. Management of gastrointestinal side effects:

   • If nausea and vomiting compromise drug delivery, medications can be given at separate times 5
   • Monitor hydration status and serum potassium if vomiting is profuse 5

3. Drug interactions:

   • Levofloxacin should be taken at least two hours before or two hours after antacids containing magnesium or aluminum, sucralfate, metal cations, or multivitamin preparations with zinc 3

Conclusion

The combination of levofloxacin and ethambutol provides an effective and safe treatment option for tuberculosis patients with hepatotoxicity. This regimen avoids the major hepatotoxic drugs (isoniazid, rifampin, and pyrazinamide) while maintaining efficacy against TB.