NULL is an oral antifibrotic medicine belonging to the class of tyrosine kinase inhibitors (TKIs). It is primarily prescribed to slow the progression of Idiopathic Pulmonary Fibrosis (IPF), Systemic Sclerosis-associated Interstitial Lung Disease (SSc-ILD), and other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype. NULL works by blocking multiple cellular signalling pathways that drive lung scarring, thereby reducing the rate of lung function decline. Although it does not cure fibrotic lung disease, long-term use helps preserve respiratory capacity and supports better disease outcomes.

NULL contains nintedanib, a small-molecule intracellular tyrosine kinase inhibitor specifically developed to address the pathological fibrosis seen in chronic interstitial lung diseases. In conditions such as idiopathic pulmonary fibrosis, the normal healing process of the lungs becomes dysregulated. Instead of repairing minor injury, the lungs develop excessive scar tissue, leading to progressive thickening and stiffening of the lung interstitium. This reduces lung elasticity, impairs oxygen transfer, and causes gradually worsening breathlessness.

Patients with fibrotic lung disease often experience symptoms such as shortness of breath on exertion, persistent dry cough, fatigue, and reduced exercise tolerance. Over time, these symptoms may progress to severe respiratory impairment. Traditional anti-inflammatory medicines and immunosuppressants offer limited benefit in purely fibrotic disease. NULL was developed to specifically target fibrotic pathways rather than inflammation alone.

NULL inhibits several receptor tyrosine kinases, including platelet-derived growth factor receptors, fibroblast growth factor receptors, and vascular endothelial growth factor receptors. These growth factors play a central role in activating fibroblasts and promoting collagen deposition in lung tissue. By blocking these pathways, NULL slows fibroblast proliferation, migration, and transformation into scar-forming cells.

Clinical trials have consistently shown that NULL significantly reduces the annual rate of decline in forced vital capacity (FVC), which is a key measure of lung function. While patients may not experience immediate symptom relief, slowing disease progression is clinically meaningful and can delay respiratory failure, hospitalisation, and the need for lung transplantation.

NULL is intended for long-term use and should be taken continuously unless discontinued by a specialist. Because it can affect liver enzymes and gastrointestinal tolerance, regular medical monitoring is essential. When used appropriately, NULL plays a vital role in improving disease stability and maintaining quality of life for patients with progressive fibrosing lung disorders.

NULL is indicated for the treatment of the following conditions:

Idiopathic Pulmonary Fibrosis (IPF):

Used to slow the progression of lung scarring and reduce the rate of decline in lung function in adults with IPF.

Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD):

Helps limit the progression of fibrotic lung involvement in patients with systemic sclerosis.

Chronic Fibrosing Interstitial Lung Diseases with a Progressive Phenotype:

Prescribed to slow disease worsening in other fibrosing ILDs that continue to progress despite standard treatment.

Disease-Modifying Action:

Targets key molecular pathways involved in fibrosis, helping slow disease progression rather than only relieving symptoms.

Preserves Lung Function:

Clinically proven to reduce the annual decline in forced vital capacity (FVC), a key measure of lung capacity.

Broad ILD Coverage:

Effective across multiple fibrosing lung diseases, including autoimmune-related and progressive ILDs.

Long-Term Management Option:

Suitable for continuous, long-term use under specialist supervision.

Oral Therapy Convenience:

Available as capsules, avoiding the need for injections or hospital-based treatments.

Most patients experience some side effects, particularly during the early phase of treatment. These are often manageable with dose adjustment and supportive care.

Common Side Effects

• Diarrhoea

• Nausea

• Vomiting

• Abdominal discomfort

• Reduced appetite

• Weight loss

• Fatigue

• Elevated liver enzymes

Less Common Side Effects

• Headache

• Dizziness

• High blood pressure

• Skin rash

Serious Side Effects (Seek immediate medical advice)

Stop the medicine and seek urgent medical attention:

• Signs of Liver Injury: Yellowing of the skin or eyes (jaundice), dark urine, persistent nausea, severe fatigue, or right-upper abdominal pain.

• Severe or Persistent Diarrhoea: Leading to dehydration.

• Bleeding Events: Unusual bruising, nosebleeds, or gastrointestinal bleeding.

• Cardiovascular Events (Rare): Chest pain or symptoms suggestive of clot formation.

• Gastrointestinal Perforation (Very Rare): Severe abdominal pain with fever.

• Dosage: The standard adult dose is 150 mg twice daily, taken approximately 12 hours apart. In patients who experience intolerance, the dose may be reduced to 100 mg twice daily.
• Administration: Capsules should be taken with food to minimise gastrointestinal side effects. Swallow whole with water. Do not chew, crush, or open the capsules.
• Consistency: Take the medicine at the same times each day. Do not stop treatment without consulting your specialist, even if symptoms appear stable.

NULL works by targeting the biological processes responsible for lung fibrosis.

• Tyrosine Kinase Inhibition: NULL inhibits multiple receptor tyrosine kinases involved in fibrotic signalling pathways.

• Growth Factor Blockade: It blocks receptors for platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF), all of which drive fibroblast activation.

• Anti-Fibrotic Effect: By suppressing fibroblast proliferation, migration, and collagen deposition, it slows the formation of scar tissue in the lungs.

• Overall Outcome: Reduced progression of lung fibrosis and preservation of lung elasticity and function over time.

• Take with Food: Always take each dose with a full meal to improve tolerance.

• Manage Diarrhoea Early: Start antidiarrhoeal treatment promptly and maintain fluid intake to prevent dehydration.

• Liver Monitoring: Regular blood tests to monitor liver enzymes are essential, especially during the first months of therapy.

• Report Bleeding: Inform your doctor immediately if you notice unusual bruising, bleeding, or black stools.

• Do Not Stop Abruptly: Continue taking NULL as prescribed unless advised otherwise by your specialist.

• Store at room temperature (below 25°C).

• Keep the capsules in the original blister pack to protect from moisture.

• Protect from heat and direct sunlight.

• Keep out of reach of children.

There are no specific food restrictions while taking NULL. However, maintaining a balanced, nutritious diet is important, as reduced appetite and weight loss are common during treatment. Adequate hydration is essential, particularly if diarrhoea occurs. Excessive alcohol intake should be avoided, as it may increase the risk of liver-related side effects.

• Anticoagulants (e.g., Warfarin): Concomitant use may increase the risk of bleeding. Close clinical and laboratory monitoring is required.

• Antiplatelet Medicines (e.g., Aspirin, Clopidogrel): May further increase bleeding risk; use cautiously under medical supervision.

• Strong P-glycoprotein (P-gp) Inhibitors (e.g., Ketoconazole, Erythromycin): May increase NULL blood levels, raising the risk of side effects.

• Strong P-gp Inducers (e.g., Rifampicin, Carbamazepine, Phenytoin): May reduce the effectiveness of NULL by lowering its concentration.

• NSAIDs (e.g., Ibuprofen, Naproxen): May increase the risk of gastrointestinal complications; caution is advised.

• Hepatic Impairment (Liver Disease): Increased risk of hepatotoxicity. Use with caution in patients with liver disease. Regular monitoring of liver function tests (LFTs) is mandatory. Dose adjustment or discontinuation may be required in moderate to severe impairment.

• Bleeding Disorders: NULL may increase the risk of bleeding due to its anti-angiogenic properties. Use with caution in patients with a history of bleeding.

• Cardiovascular Disease: Caution is advised in patients with a history of arterial thromboembolic events, such as heart attack or stroke.

• Gastrointestinal Disorders: Use cautiously in patients with a history of peptic ulcer disease, diverticular disease, or recent gastrointestinal surgery due to a rare risk of gastrointestinal perforation.

• Renal Impairment (Kidney Disease): Generally safe in mild to moderate renal impairment, but limited data are available in severe kidney disease; careful monitoring is advised.

The usual recommended dose is 150 mg twice daily, taken approximately 12 hours apart. If side effects occur, the dose may be reduced to 100 mg twice daily or temporarily interrupted, based on clinical judgement.

Overdose may result in severe gastrointestinal symptoms, including nausea, vomiting, diarrhoea, or significant elevation of liver enzymes. Seek immediate medical attention. Treatment is supportive and may include monitoring liver function, fluid replacement, and symptom management under medical supervision.

If you miss a dose, do not take an extra dose to compensate. Skip the missed dose and take the next one at the regular scheduled time. Doubling the dose may increase the risk of side effects.