nerandomilast

Action and Spectrum

Action and spectrum:  

It acts as a phosphodiesterase 4 (PDE4) inhibitor, showing a selective affinity for the PDE4B isoenzyme. This selectivity contributes to its antifibrotic and immunomodulatory effects. By blocking PDE4B activity, the drug increases intracellular cyclic AMP (cAMP) concentrations, leading to a reduction in pro-fibrotic growth factors and inflammatory cytokines that are typically elevated in idiopathic pulmonary fibrosis (IPF). 

Drug Interaction

Adverse Reaction

Frequency Defined  

1-10%
Vasculitis (1%)
Amylase increased (1%)
Asthenia (4-5%)
Dizziness (5-6%)
Back pain (5-6%)
Vomiting (5-6%)
Headache (6-7%)
Fatigue (7-8%)
Nausea (8-9%)
Decreased appetite (9%) 

>10%
Weight decreased (10-11%)
Depression (11-12%)
Upper respiratory tract infection (11-13%)
Respiratory infection, COVID-19 (13-16%)
Diarrhea (31-42%) 

Black Box Warning

Black Box Warning  

None 

Contraindication / Caution

Contraindication/Caution:  

Contraindication  

None 

Cautions  

Drug interactions 

Pregnancy / Lactation

Pregnancy Warnings:  

Pregnancy category: N/A  

Lactation: Excretion in human breastmilk is unknown  

Pregnancy categories:  

Category A: Satisfactory and well-controlled studies show no evidence of risk to the fetus in the first trimester or in the later trimester.  

Category B: No evidence of risk to fetus found in animal reproduction studies and there are not enough studies on pregnant women.  

Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women.  

Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits.  

Category X: Drugs listed in this category clearly outweigh risks over benefits. These category drugs should be prohibited for pregnant women.   

Category N: There is no data available for the drug under this category.   

Pharmacology

Pharmacology:  

It acts as a phosphodiesterase 4 (PDE4) inhibitor, showing a selective affinity for the PDE4B isoenzyme. This selectivity contributes to its antifibrotic and immunomodulatory effects. By blocking PDE4B activity, the drug increases intracellular cyclic AMP (cAMP) concentrations, leading to a reduction in pro-fibrotic growth factors and inflammatory cytokines that are typically elevated in idiopathic pulmonary fibrosis (IPF). 

Pharmacokinetics:  

Absorption  

After oral administration, the drug exhibits a bioavailability of approximately 73%, with peak plasma concentrations achieved within 1 to 1.25 hours. A steady-state level is typically reached after about four days of consistent dosing. 

Distribution  

About 77% of the drug binds to plasma proteins, and it has an apparent volume of distribution (Vd) of around 93 L. 

Metabolism  

The drug undergoes hepatic metabolism, mainly through the CYP3A enzyme system, with minor contributions from multiple UGT enzymes. A chiral inversion process converts the pharmacologically active R-enantiomer; the major circulating form into the inactive S-enantiomer, which is a minor metabolite. 

Excretion and Elimination  

For elimination, the drug has a half-life of approximately 17 hours and a clearance rate of about 15.2 L/hour. Excretion occurs primarily through the feces (58%), with 14% excreted unchanged, and through the urine (36%), with 13% unchanged. 

Adminstartion

Administration:  

 The mode of administration is oral. 

Patient Information Leaflet

Patient information leaflet  

Generic Name: nerandomilast 

Why do we use nerandomilast? 

Nerandomilast is being developed for the treatment of idiopathic pulmonary fibrosis, a chronic, progressive lung disease characterized by scarring (fibrosis) of the lung tissue. 

It helps reduce inflammation and fibrosis by inhibiting PDE4, which increases intracellular cAMP levels and modulates inflammatory pathways.