Nerandomilast Dosing and Administration
The recommended dosage of nerandomilast is 18 mg orally twice daily, taken with or without food, for the treatment of idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF). 1
Standard Dosing Regimen
- Standard dose: 18 mg orally twice daily
- Food: Can be taken with or without food (no clinically relevant differences in pharmacokinetics with high-fat meals) 1
- Timing: Steady state is reached in approximately 4 days 1
Dose Modifications
Concomitant Strong CYP3A Inhibitors
Reduce the dose to 9 mg twice daily when using nerandomilast with strong CYP3A inhibitors (e.g., itraconazole, ketoconazole, clarithromycin), as these medications increase nerandomilast exposure by 2.2-fold, potentially increasing adverse reaction risk 1.
Concomitant Pirfenidone Use
Maintain the 18 mg twice daily dose when using nerandomilast with pirfenidone. Do not reduce to 9 mg twice daily, as pirfenidone decreases nerandomilast exposure by approximately 50%, and the 9 mg dose showed no efficacy when combined with pirfenidone in clinical trials 1.
Medications to Avoid
Avoid concomitant use with moderate or strong CYP3A inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin), as these are expected to decrease nerandomilast exposure and reduce efficacy 1.
Missed Dose Instructions
The approach depends on timing:
Within 3 days of missed dose: Administer as soon as possible and resume the original once-weekly schedule. Monitor fasting blood glucose closely during this period.
More than 3 days after missed dose: Administer as soon as possible, but the dosing schedule will shift to the new day of administration. If returning to the original schedule is desired, extend subsequent dosing intervals by 1-3 days each week until reaching the original administration day.
Note: These missed dose instructions appear to reference weekly dosing from insulin icodec guidelines 2 and may not apply to nerandomilast's twice-daily regimen. The FDA label does not provide specific missed dose guidance for nerandomilast 1.
Special Populations
Renal Impairment
No dose adjustment required for mild, moderate, or severe renal impairment (eGFR ≥15 mL/min/1.73 m²). End-stage renal disease has not been studied 1.
Hepatic Impairment
No dose adjustment required for mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. Severe hepatic impairment (Child-Pugh Class C) has not been studied 1.
Age, Weight, Sex, Race
No dose adjustments needed based on age (18-90 years), body weight (31-143 kg), sex, or race 1.
Monitoring Recommendations
Weight Monitoring
Monitor weight regularly, particularly when used with nintedanib. Weight decrease occurred in 12-13% of patients on nerandomilast 18 mg twice daily 1. Consider clinical significance if substantial weight loss occurs.
Gastrointestinal Adverse Effects
Diarrhea is the most common adverse reaction (41.3% with 18 mg twice daily vs. 16.0% with placebo). Most cases are mild to moderate and occur within the first 3 months of treatment 1, 3. Diarrhea led to discontinuation in only 4% of patients using nerandomilast with nintedanib and 1% without nintedanib 1.
Malignancy Surveillance
Increased rates of neoplasms were observed in PPF patients (5% with nerandomilast vs. 3% with placebo), including non-melanoma skin cancers and small cell lung cancer. Maintain appropriate cancer screening protocols 1.
Clinical Efficacy Context
Nerandomilast demonstrated dose-dependent efficacy in slowing FVC decline:
- 18 mg twice daily: Reduced FVC decline by 68.8 mL vs. placebo at 52 weeks in IPF 3
- 9 mg twice daily: Reduced FVC decline by 44.9 mL vs. placebo at 52 weeks in IPF 3
- Both doses showed similar efficacy in PPF (67.2 mL and 81.1 mL improvement vs. placebo, respectively) 4
The 18 mg twice daily dose is preferred based on greater efficacy in IPF and consistent safety profile across both indications.