Table 4. Dosing of MDR-TB agents in patients with renal impairment.

Mycobacterial agent and usual dose	Degree of renal impairment (Cr clearance)	Renal replacement therapy	Special prescriber points
Aminoglycosides (99-101) (Cm, Km, Am) 15–20 mg/kg	Dosing should be adjusted to achieve undetectable plasma trough levels at all levels of renal impairment	Dosing should be adjusted to achieve undetectable plasma trough levels	Must be AVOIDED if possible; main route of clearance is renal; 3x/week vs. daily has no difference in oto/nephrotoxicity; dose adjustment and therapeutic drug monitoring required due to toxicity risk and changes in drug clearance over time; monitoring should include regular U&Es to assess renal function along with clinical assessment, audiometry
Pyrazinamide (102-104) 25–30 mg/kg/day 1.5 g for 50 kg, 2 g for >50 kg	≥30 mL/min: no dose adjustment required; <30 mL/min: 25–30 mg/kg three times per week	25–30 mg/kg three times/week after dialysis	Can be used safely in renal disease; main route of clearance is hepatic with active metabolites undergoing some renal clearance; monitor LFTs for hepatotoxicity; monitor for gout due to reduced uric acid clearance in renal failure
Ethambutol (103-105), 15–25 mg/kg/day (103)	≥30 mL/min: No dose adjustment required; <30mL/min: 15–25 mg/kg three times per week	15–25 mg/kg three times a week; dialysis does not eliminate drug significantly	AVOID use if possible; main route of clearance is renal; ocular toxicity is a significant concern in patients with renal disease
Ethionamide (106), 15–20 mg/kg/day in divided doses	No dose adjustment required	No dose adjustment required	Main route of clearance is hepatic; monitor for neuropathy and hepatotoxicity
Cycloserine (106), 10–15 mg/kg/day in divided doses	≥30 mL/min: no dose adjustment required; <30 mL/min: 250 mg daily or 500 mg alternate days	250 mg daily or 500 mg alternate days given after hemodialysis	AVOID if possible in renal disease. As the main route of clearance is renal; Increased risk of significant neurotoxicity; plasma level monitoring should be used if available
Para-aminosalicylic acid (PAS) (106) 8–12 g/day	No dose adjustment required	Hemodialysis eliminates it’s the active metabolite. Dosing should therefore be given post dialysis	Use with extreme caution in renal disease as the main route of clearance is renal; increased risk of acidosis and gastrointestinal side effects
Linezolid 600 mg/day	No dose adjustment required	No dose adjustments required	Main route of clearance is hepatic with some renal clearance; increased risk of haematological toxicity and peripheral neuropathy
Isoniazid (103,107), 16–18 mg/kg	No dose adjustment required	No dose adjustments required; hemodialysis does not eliminate drug significantly	Co-administer with pyridoxine
Clofazamine (106), 100 mg daily	No dose adjustment needed	No dose adjustment needed	Monitor QTc when used concurrently with other QTc prolonging agents like bedaquiline, delamanid and fluoroquinolones in patients with renal insufficiency
Fluoroquinolones (108) moxifloxacin 400 mg daily; levofloxacin (108,109) 750–1,000 mg daily	Moxifloxacin: no dose adjustments needed; levofloxacin: 30–50 mL/min (750–1,000 mg), <30 mL/min (750–1,000 mg three times per week)	Moxifloxacin: no dose adjustments necessary; levofloxacin: 750–1,000 mg alternate days	Moxifloxacin is predominantly cleared by the hepatobiliary route while levofloxacin has significant renal clearance in addition; there may be a higher risk of neurotoxicity and tendinopathies when using fluoroquinolones in advanced renal insufficiency; avoid concomitant administration of antacids, phosphate binders, calcium, iron or aluminium containing medications to avoid mal-absorption