Table 3:

Dosing Guidelines for Drugs Used in the Management of NTM Pulmonary Disease

Drug	Daily Dosing	Thrice Weekly Dosing	Hepatic Impairment	Renal Impairment
Oral
Azithromycin	250–500 mg per day	500 mg per day	N/A	N/A
Ciprofloxacin	500–750 mg twice per day	N/A	N/A	250–500 mg dosed at intervals according to CrCl
Clarithromycin	500 mg twice per day	500 mg twice per day	N/A	Reduce dose by 50% if CrCl<30 mL/min
Clofaziminea	100–200 mg per day	N/A	Caution in severe hepatic impairment	N/A
Doxycycline	100 mg once to twice a day	NA	NA	NA
Ethambutol	15 mg/kg per day	25 mg/kg per day	N/A	Increase dosing interval (e.g., 15–25 mg/kg, 3 times per week)
Isoniazid	5 mg/kg up to 300 mg per day	N/A	Caution	N/A
Linezolid	600 mg once or twice per dayb	N/A	N/A	N/A
Moxifloxacin	400 mg per day	N/A	N/A	N/A
Rifabutin	150–300 mg per day (150 mg per day with clarithromycin)	300 mg per day	Caution	Reduce dose by 50% if CrCl<30 mL/min
Rifampicin (rifampin)	10 mg/kg (450 mg or 600 mg) per day	600 mg per day	Caution	N/A
Trimethoprim/sulfamethoxazole	800 mg/160 mg tab twice daily	NA	Caution	Reduce dose by 50% if CrCl15–30 mL/min
Parenteral
Amikacin (IV)	10–15 mg/kg per dayc, adjusted according to drug level monitoringd	15–25 mg/kg per dayc, adjusted according to drug level monitoringd	N/A	Reduce dose or increase dosing interval (e.g., 15 mg/kg, 2–3 times per week)
Cefoxitin (IV)	2–4 g 2–3 times daily (maximum daily dose is 12 g/day)	N/A	N/A	Reduce dose or increase dosing interval
Imipenem (IV)	500–1000 mg, 2–3 times per day	N/A	N/A	Reduce dose or increase dosing interval
Streptomycin (IV or IM)	10–15 mg/kg per day, adjusted according to drug level monitoring	15–25 mg/kg per day, adjusted according to drug level monitoring	N/A	Reduce dose or increase dosing interval (e.g., 15 mg/kg, 2–3 times per week)
Tigecycline (IV)	25–50 mg once or twice per dayb	N/A	25 mg once or twice daily per day in severe hepatic impairment	N/A
Inhalation
Amikacin liposome inhaled suspension	590 mg per day	N/A	N/A	N/A
Amikacin, parenteral formulation	250–500 mg per day	NA	NA	NA

N/A – not applicable

^aClofazimine availability varies by country. In the United States, an investigational new drug application is required.

^bMost experts recommend once daily dosing of linezolid and tigecycline due to the high rate of drug-related adverse reactions associated with twice daily dosing

^cThe use of the described regimens for 15 weeks was associated with permanent ototoxicity in approximately one third of patients, and the risk was associated with age and cumulative dose [154]. Given the high rates of ototoxicity, risks and benefits should be carefully considered in light of the goals of therapy. Clinicians should consider lower dose ranges and probably rely on intermittent dosing when more prolonged therapy is employed.

^dDrug level monitoring; Trough < 5 mg/L, Peak with daily dosing 35–45 μg/ml, Peak with intermittent dosing 65–80 μg/ml [154].