NERANDOMILAST TAB

Clinical Criteria Summary

• Treatment of idiopathic pulmonary fibrosis (IPF) in adult patients
• Treatment of non-IPF interstitial lung disease with progression, also known as progressive pulmonary fibrosis (PPF), in adult patients

• IPF: Patients 40 years of age or older; diagnosis confirmed by investigator per guidelines based on high-resolution computed tomographic (CT) scan and centrally confirmed
• PPF: Patients 18 years and older; must have a non-IPF ILD diagnosis, fibrotic lung disease ≥10% by HRCT within the past 12 months, FVC ≥45% of predicted, and DL of ≥25% of predicted
• PPF progression criteria (within prior 24 months): relative FVC decline ≥10%; OR FVC decline of 5 to 10% with worsening respiratory symptoms and/or increased extent of fibrotic changes on imaging; OR worsening respiratory symptoms and increased extent of fibrotic changes on imaging
• IPF diagnosis requires exclusion of other identifiable causes of ILD, HRCT showing usual interstitial pneumonia (UIP) or probable UIP pattern, or indeterminate pattern for UIP with histologic confirmation; pulmonary function tests assess pattern and severity

• Usual dose: 18 mg twice daily, administered every 12 hours without regard to food
• Reduced dose (9 mg twice daily): For patients unable to tolerate 18 mg twice daily or receiving concomitant strong CYP3A4 inhibitors
• Dose with pirfenidone: Maintain full dose of 18 mg twice daily; do not reduce dose due to drug interaction

• Contraindications: None stated
• Exclude patients with active vasculitis, severe depression, suicidal behavior or ideation
• Exclude patients with elevated hepatic transaminases >2.5 times the upper limit of normal or total bilirubin >1.5 times the upper limit of normal
• Exclude patients with estimated glomerular filtration rate (eGFR) ≤ 30 ml/min/1.73 m2
• Avoid use in patients receiving certain immunomodulatory medications: prednisone equivalent dose >15 mg daily, cyclophosphamide, tocilizumab, mycophenolate, pirfenidone, or rituximab
• Pregnancy: May increase risk of fetal loss based on animal studies; no available data in pregnant women

• Monitor for gastrointestinal adverse events, particularly diarrhea (generally occurs within the first three months), nausea, and decreased appetite/weight
• Monitor for psychiatric adverse events, including depression and suicidality, which may lead to treatment discontinuation
• Discontinuations due to adverse events were more common with nerandomilast vs placebo; diarrhea was the most common adverse reaction leading to discontinuation, occurring more frequently with concomitant nintedanib

• Strong CYP3A4 inhibitors: Reduce dose to 9 mg twice daily due to increased exposure
• Moderate or strong CYP3A inducers: Avoid concomitant use due to decreased exposure
• Pirfenidone: Prescribe full dose of 18 mg twice daily; do not reduce dose due to reduced exposure

Severe hepatic impairment (Child Pugh C)
End stage renal disease (eGFR less than 15 ml/min/1.73 m2)
Recent, active, or uncontrolled vasculitis
Severe depression or suicidal ideation or behavior unless a mental health consultant concurs with nerandomilast treatment
Concurrent use of CYP3A inducer

Care provided by VA/VA Community Care pulmonologist experienced in the management of interstitial lung disease (ILD)
Confirmed interstitial pulmonary fibrosis (IPF) diagnosis or non-IPF interstitial lung disease with progression, using clinical, radiologic and if applicable, histopathologic information
Monotherapy when there is a contraindication, intolerance, or inadequate response to nintedanib (and pirfenidone in IPF) or additive therapy to either pirfenidone or nintedanib when further efficacy is desired

Relative decline in FVC of 10% or more of predicted within past 24 months
Relative decline in FVC of 5% to less than 10% of predicted combined with either worsening of respiratory symptoms or increased extent of fibrotic changes on imaging
Worsening of respiratory symptoms and increased extent of fibrotic changes on imaging

Patients continuing treatment with pirfenidone and adding nerandomilast must be prescribed the 18 mg twice daily dose (nerandomilast dose should not be reduced)
Patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and use of effective contraception during therapy
Patients who are lactating and providing breastmilk to infant: Counseling provided on potential risks vs. benefits of treatment

IPF diagnosis confirmation requires exclusion of other identifiable causes of ILD, high resolution CT scan showing usual interstitial pneumonia (UIP) pattern or probable UIP pattern, or indeterminate pattern for UIP with histological confirmation of IPF
Progressive pulmonary fibrosis (PPF) is a pattern of disease progression requiring documented markers for progression
Diarrhea occurs more frequently when combined with nintedanib and may reduce tolerability