How Do Pulmonary Tyrosine Kinase Inhibitors Work?

Pulmonary tyrosine kinase inhibitors are medications used to treat progressive lung diseases such as pulmonary fibrosis which cause scarring and thickening of the lungs resulting in loss of lung function. Pulmonary tyrosine kinase inhibitors prevent scar tissue formation in the lungs by inhibiting the activity of tyrosine kinase.

Tyrosine kinases are enzymes that play a key role in intercellular communication and many cellular functions including regulation of cell growth, proliferation, differentiation, and survival. Tyrosine kinases respond to growth factor proteins and activate a downstream signaling cascade that initiates action within the cell.

In fibrotic lung diseases, tyrosine kinases promote abnormal growth of scar tissue which replaces normal lung tissue, progressively affecting lung function. Pulmonary tyrosine kinase inhibitors prevent tyrosine kinases from promoting scar tissue growth in the lungs.

Pulmonary tyrosine kinase inhibitors prevent the activity of many tyrosine kinases implicated in pulmonary fibrosis including: 

• Vascular endothelial growth factor receptors (VEGFR) that play a role in blood vessel growth
• Fibroblast growth factor receptors (FGFR) that promote cell proliferation during tissue repair
• Platelet-derived growth factor receptors (PDGFR) that help repair damage to blood vessel walls

Pulmonary tyrosine kinase inhibitors are oral capsules used to slow down the progression of disease in lung diseases that cause lung scarring and progressive decline in lung function, which include:

FDA-approved:

• Idiopathic pulmonary fibrosis
• Chronic fibrosing interstitial lung diseases (ILD) with a progressive phenotype
• Systemic sclerosis-associated interstitial lung disease (SSc-ILD)

Orphan designation:

• Mesothelioma (cancer that develops in the tissue lining the lungs).

Side effects of pulmonary tyrosine kinase inhibitors may include the following:

• Diarrhea
• Nausea
• Abdominal pain
• Vomiting
• Decreased appetite
• Decreased weight
• Elevated liver enzymes
• Skin ulcer
• Fatigue
• Bleeding events
• Headache
• Hypertension (high blood pressure)
• Arterial thromboembolic events (blood clot block in arteries)
• Myocardial infarction (heart attack)
• Bronchitis (inflammation of the bronchial passage)
• Hypothyroidism
• Pyrexia (fever)
• Back pain
• Dizziness
• Pneumonia
• Malignant lung neoplasm (abnormal tissue growth)
• Gastrointestinal perforation
• Pancreatitis (inflammation of the pancreas)
• Thrombocytopenia (low platelet count in the blood)
• Drug-induced liver injury
• Rash
• Pruritus (itching)
• Alopecia (hair loss)

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of the FDA-approved pulmonary tyrosine kinase inhibitor drug are:

• nintedanib
• Ofev