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 (decreased nerandomilast exposure)

Care provided by VA/VA Community Care pulmonologist experienced in the management of interstitial lung disease (ILD)
Confirmed idiopathic 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 for additive therapy to either pirfenidone or nintedanib when further efficacy is desired

Relative decline in FVC of 10% or more of predicted
Relative decline in FVC of 5% to less than 10% of predicted and: 1) worsening of respiratory symptoms; or 2) 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: Prescribed the 18 mg twice daily dose of nerandomilast (nerandomilast dose should not be reduced)
For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy
For patients who are lactating and providing breastmilk to infant: Counseling provided on potential risks vs. benefits of treatment