Moxifloxacin Dosing in Severe CKD with Active TB
For a patient with severe chronic kidney disease and active tuberculosis, moxifloxacin should be dosed at 400 mg once daily without any adjustment for renal function. 1, 2
Key Dosing Principle
Unlike levofloxacin and aminoglycosides, moxifloxacin does not require dose reduction or interval extension in renal impairment, including severe CKD and end-stage renal disease. 1, 3, 2
Evidence Supporting Standard Dosing
The FDA drug label explicitly states that moxifloxacin pharmacokinetic parameters are not significantly altered in mild, moderate, severe, or end-stage renal disease, and no dosage adjustment is necessary in patients with renal impairment, including those requiring hemodialysis or peritoneal dialysis. 2
The 2019 ATS/CDC/ERS/IDSA guidelines for drug-resistant TB confirm that moxifloxacin requires "no change needed" for reduced renal function, in stark contrast to levofloxacin which requires three-times-weekly dosing. 1
The 2016 ATS/CDC/IDSA guidelines for drug-susceptible TB similarly document that moxifloxacin maintains its 400 mg once daily dosing regardless of creatinine clearance. 1
Comparison with Levofloxacin
This is a critical distinction from levofloxacin, which undergoes 80% renal clearance and requires dose adjustment to 750-1000 mg three times weekly when creatinine clearance falls below 50 mL/min. 1, 4, 5
Why Moxifloxacin Differs
Moxifloxacin undergoes primarily hepatic metabolism rather than renal clearance, making it uniquely suited for patients with severe CKD. 3
While metabolite accumulation occurs (sulfate conjugate M1 increases 1.4-1.5-fold, glucuronide conjugate M2 increases 7.5-fold in dialysis patients), these metabolites are not microbiologically active and the clinical significance has not been established. 2
Standard Dosing Regimen
Administer 400 mg once daily orally or intravenously. 1
Higher Dose Considerations
Doses of 600-800 mg daily have been used when isolates show resistance to ofloxacin or when minimum inhibitory concentrations suggest higher doses may overcome resistance. 1
Research suggests 800 mg daily may provide superior resistance suppression (93% target attainment vs 59% for 400 mg), but long-term safety data at doses above 400 mg/day are limited. 1, 6
For standard drug-susceptible TB in a patient with severe CKD, maintain the 400 mg daily dose unless drug susceptibility testing indicates resistance requiring higher doses. 1
Critical Caveats
Hepatic Considerations
While no dose adjustment is needed for renal impairment, use moxifloxacin with caution if the patient also has hepatic insufficiency due to risk of QT prolongation from metabolic disturbances. 2
Hepatic insufficiency increases exposure to sulfate and glucuronide metabolites (3.9-5.7-fold for M1, 1.5-fold for M2), though clinical significance is unclear. 2
Drug Interactions
Do not administer moxifloxacin within 2 hours of antacids or medications containing divalent cations (calcium, magnesium, iron, aluminum), as these significantly reduce bioavailability. 1
Rifamycins reduce moxifloxacin plasma concentrations by up to 31%, though clinical relevance for TB treatment is unclear. 7
Timing with Dialysis
If the patient requires hemodialysis or peritoneal dialysis, moxifloxacin can be given at any time as it is not significantly removed by dialysis (only 9% by hemodialysis, 3% by peritoneal dialysis). 2
This contrasts with other TB drugs like pyrazinamide and ethambutol, which should be given post-dialysis. 1
Monitoring
Monitor for QT prolongation, particularly in patients with electrolyte disturbances common in severe CKD (hypokalemia, hypomagnesemia), as moxifloxacin can prolong the QT interval. 2