Brensocatib Dose Reduction in Bronchiectasis
Yes, the dose of brensocatib can be decreased from 25mg to 10mg daily in patients with bronchiectasis, as both doses have demonstrated clinical efficacy with potentially fewer side effects at the lower dose.
Evidence for Dose Reduction
- In the phase II WILLOW trial, both brensocatib 10mg and 25mg doses were effective in prolonging time to first exacerbation compared to placebo in patients with bronchiectasis 1
- The 10mg dose showed a slightly better exacerbation rate reduction (incidence-rate ratio of 0.64) compared to the 25mg dose (incidence-rate ratio of 0.75) 1
- Both doses effectively reduced sputum neutrophil elastase activity over the 24-week treatment period 1
- Pharmacokinetic/pharmacodynamic evaluations support the clinical efficacy of both 10mg and 25mg doses 2
Safety Considerations
- The incidence of dental and skin adverse events was higher with brensocatib treatment compared to placebo 1
- Post-hoc analyses of the WILLOW trial showed similar safety profiles across different patient subgroups for both doses 3
- A pharmacokinetic study demonstrated that brensocatib was well tolerated in both Japanese and White participants at doses of 10mg, 25mg, and 40mg 4
- Periodontal evaluations showed no significant changes in periodontal status with either 10mg or 25mg doses after 24 weeks of treatment 5
Dosing Recommendations
- Pharmacokinetic/pharmacodynamic modeling supports the use of both 10mg and 25mg once-daily dosing regimens 2
- Based on the predicted likelihood of clinical outcomes, both 10mg and 25mg doses were selected for phase III clinical trials 2
- The elimination half-life of brensocatib ranges from 22 to 28 hours, supporting once-daily dosing at either dose level 4
Factors to Consider When Reducing Dose
- Patient tolerance to the medication (if experiencing adverse effects at 25mg) 4
- Similar efficacy was observed between doses, with the 10mg dose actually showing a slightly better exacerbation rate reduction 1
- Brensocatib can be administered with or without food at either dose 4
- No dose adjustment is necessary based on age or in those with mild to moderate renal impairment 2
Monitoring After Dose Reduction
- Continue to monitor for clinical response, particularly exacerbation frequency 1
- Monitor for adverse events of special interest, including dental and skin manifestations 1, 5
- Regular dental/periodontal care should be provided to patients regardless of brensocatib dose 5
The evidence suggests that the 10mg dose provides similar clinical benefits to the 25mg dose with potentially fewer side effects, making dose reduction a reasonable approach for patients with bronchiectasis who are currently on the 25mg dose.