Pretomanid Does Not Require Renal Dose Adjustment
Pretomanid can be administered at standard dosing (200 mg daily) regardless of renal function, as it does not undergo significant renal elimination and no dose adjustment is recommended for patients with renal impairment.
Rationale for Standard Dosing
The available evidence does not identify pretomanid among drugs requiring renal dose adjustment for tuberculosis treatment. The most recent and comprehensive guideline on drug-resistant tuberculosis from the American Thoracic Society/CDC/ERS/IDSA (2019) provides detailed renal dosing guidance for multiple anti-tuberculosis agents but does not list pretomanid as requiring adjustment 1.
Comparison with Other TB Drugs Requiring Renal Adjustment
To contextualize pretomanid's dosing, it's important to understand which tuberculosis drugs do require renal adjustment:
Injectable Aminoglycosides (Require Adjustment)
- Amikacin and streptomycin require dosing frequency reduction to 2-3 times weekly in patients with decreased renal function, though the milligram dose per administration should be maintained at 15 mg/kg to preserve concentration-dependent bactericidal activity 1
- These agents cause nephrotoxicity in 2-8.7% of patients and require therapeutic drug monitoring 1
Fluoroquinolones (Variable Requirements)
- Levofloxacin requires dosing frequency reduction to 3 times weekly in renal impairment 1
- Moxifloxacin requires no dose adjustment 1
Other Second-Line Agents
- Cycloserine should not be used when creatinine clearance is <50 mL/min unless the patient is on hemodialysis, where 500 mg three times weekly or 250 mg daily is recommended 1
- Delamanid (similar newer agent to pretomanid) requires no change in mild to moderate renal insufficiency, with caution in severe insufficiency 1
Drugs Not Requiring Renal Adjustment
Several key TB drugs maintain standard dosing in renal impairment, similar to pretomanid:
- Bedaquiline: No change needed 1
- Linezolid: No renal dose adjustment necessary, supporting standard dosing even in severe impairment 1, 2
- Clofazimine: Standard dosing maintained 1
- Ethionamide/Prothionamide: No change needed 1
- Moxifloxacin: No adjustment required 1
Clinical Implications
When prescribing pretomanid as part of the BPaL regimen (bedaquiline-pretomanid-linezolid) for drug-resistant tuberculosis, none of the three components require renal dose adjustment 1. This simplifies regimen management in patients with renal impairment compared to older regimens containing aminoglycosides.
Important Caveats
- While pretomanid itself doesn't require adjustment, always assess baseline renal function before initiating any multi-drug TB regimen 1
- If pretomanid is used with other agents requiring renal adjustment (such as aminoglycosides in extended regimens), those companion drugs must be appropriately dosed 1
- Patients with severe renal impairment (creatinine clearance <30 mL/min) or on dialysis warrant closer monitoring for any unexpected adverse effects, even with drugs not requiring formal dose adjustment 3, 4