Can levofloxacin and ethambutol be used together in the continuation phase of tuberculosis (TB) treatment?

Levofloxacin and Ethambutol in Tuberculosis Continuation Phase

Yes, levofloxacin and ethambutol can be used together in the continuation phase of tuberculosis treatment, particularly in drug-resistant TB regimens. 1

Indications for Levofloxacin-Ethambutol Combination in Continuation Phase

• For MDR/RR-TB (multidrug-resistant/rifampicin-resistant TB) patients, the WHO recommends a shorter all-oral regimen with a 5-month continuation phase that includes levofloxacin, clofazimine, pyrazinamide, and ethambutol 1
• This combination is specifically indicated following a 4-6 month intensive phase of treatment with bedaquiline, fluoroquinolone, clofazimine, pyrazinamide, ethambutol, high-dose isoniazid, and ethionamide 1
• Levofloxacin is generally preferred over moxifloxacin due to fewer adverse events and less QTc prolongation when used in combination regimens 1

Drug Classification and Rationale

• In the WHO classification system for MDR-TB drugs, levofloxacin is a Group A drug (highest priority) while ethambutol is a Group C drug (used when Group A and B drugs cannot compose an effective regimen) 1
• The combination provides complementary mechanisms of action:
  • Levofloxacin: fluoroquinolone that inhibits DNA gyrase
  • Ethambutol: inhibits arabinosyl transferase, affecting cell wall synthesis 2

Dosing Considerations

• Ethambutol dosing should be weight-based, typically 15-20 mg/kg daily in the continuation phase 1
• For patients weighing 40-55 kg: 800 mg daily (14.5-20.0 mg/kg)
• For patients weighing 56-75 kg: 1,200 mg daily (16.0-21.4 mg/kg)
• For patients weighing 76-90 kg: 1,600 mg daily (17.8-21.1 mg/kg) 1

Treatment Duration

• For the shorter MDR/RR-TB regimen, the continuation phase with levofloxacin and ethambutol (plus other drugs) has a fixed duration of 5 months 1
• This follows a 4-6 month intensive phase, with the total treatment duration being 9-11 months 1

Special Considerations and Monitoring

• Regular monitoring is essential when using this combination:
  • Ethambutol requires monitoring for optic neuritis (visual acuity and color discrimination testing) 1
  • Levofloxacin requires monitoring for tendinopathy, peripheral neuropathy, and QTc prolongation 1, 3
• Drug susceptibility testing (DST) should be performed, particularly for fluoroquinolones, before initiating this combination 4
• In patients with renal impairment, dose adjustments may be necessary for both drugs 1

Potential Adverse Effects

• Levofloxacin: QTc prolongation, tendinopathy, peripheral neuropathy, and rarely drug-induced hypersensitivity syndrome 3
• Ethambutol: optic neuritis (dose-dependent), peripheral neuropathy 1
• The combination has been used successfully in various forms of TB, including genital TB, with manageable side effect profiles 5

Alternative Regimens

• For drug-susceptible TB, the standard continuation phase remains isoniazid and rifampicin for 4 months (2HRZE/4HR) 1
• The levofloxacin-ethambutol combination is primarily indicated for drug-resistant TB scenarios 1, 6
• For isoniazid-resistant TB, a regimen of rifampicin, ethambutol, pyrazinamide, and levofloxacin (RZE-Lfx) has been recommended by WHO 7

Common Pitfalls to Avoid

• Failing to confirm drug susceptibility before using this combination, particularly fluoroquinolone susceptibility 4
• Inadequate monitoring for visual side effects from ethambutol 1
• Inappropriate shortening of the continuation phase duration, which should remain fixed at 5 months for the shorter MDR-TB regimen 1
• Not recognizing potential drug interactions, particularly with medications that may further prolong QTc interval 1