Nerandomilast (Jascayd) Side Effects
The most common side effect of nerandomilast is diarrhea, occurring in approximately 36-41% of patients, followed by nausea, upper respiratory tract infections, fatigue, headache, and weight loss. 1
Most Common Adverse Reactions
Based on the FDA-approved prescribing information and clinical trial data, the following side effects occur most frequently 1, 2, 3:
Gastrointestinal Effects:
- Diarrhea (36-41% of patients) - most common adverse reaction
- Usually mild to moderate intensity
- Generally occurs within first 3 months of treatment
- Higher incidence when combined with nintedanib (49-50% vs 27% monotherapy)
- Most common reason for treatment discontinuation (1-4% of patients)
- Nausea
- Vomiting
- Decreased appetite
General Symptoms:
- Fatigue
- Headache
- Dizziness
- Back pain
Infectious Complications:
- COVID-19
- Upper respiratory tract infections
Metabolic Effects:
- Weight loss/decrease (8-13% of patients)
- More common with concomitant nintedanib use (10-12%)
- Consider discontinuation if >5% weight loss from baseline occurs 1
Psychiatric:
- Depression (reported in clinical trials) 1
Serious Adverse Reactions
Malignancies:
- Increased incidence observed in progressive pulmonary fibrosis trials (5% nerandomilast vs 3% placebo) 1
- Specific cancers reported:
- Non-melanoma skin cancers (basal cell carcinoma, squamous cell carcinoma)
- Small cell lung cancer (1% with 18 mg dose)
Cardiovascular:
- Atrial fibrillation (3% with 18 mg dose, 2% with 9 mg dose, <1% placebo) 1
Embryo-Fetal Toxicity:
- May cause fetal loss based on animal studies
- Increased embryo-fetal losses at 5× the maximum recommended human dose in rats 1
Important Clinical Considerations
Drug-Specific Warnings:
- Diarrhea risk increases substantially when combined with nintedanib - counsel patients accordingly 1
- Monitor weight regularly; discontinue if >5% loss from baseline 1
- Patients prone to dehydration (elderly) may experience more severe gastrointestinal effects potentially requiring hospitalization 1
Comparative Tolerability: The overall serious adverse event rate was balanced across treatment groups in both FIBRONEER-IPF and FIBRONEER-ILD trials, suggesting nerandomilast does not increase serious complications beyond the underlying disease 2, 3. Treatment discontinuation rates due to adverse events remained relatively low (1-4% for diarrhea), indicating acceptable tolerability for most patients 1.
Pregnancy Considerations: Advise pregnant women and females of reproductive potential about the risk of fetal loss. The drug should only be used in pregnancy if benefit justifies potential fetal risk 1.