Nintedanib Accord Healthcare (Nintedanib)

Nintedanib acts on multiple receptor tyrosine kinases involved in fibrotic remodeling and tumor angiogenesis.

• Idiopathic pulmonary fibrosis: slows the decline in lung function and reduces disease progression.
• Systemic sclerosis‑associated interstitial lung disease: helps preserve vital capacity and delay worsening of respiratory symptoms.
• Non‑small cell lung cancer (in combination therapy): contributes to tumour control when used with standard chemotherapy regimens.

• Nintedanib inhibits the intracellular kinase activity of vascular endothelial growth factor receptors (VEGFR 1‑3), platelet‑derived growth factor receptors (PDGFR‑α/β) and fibroblast growth factor receptors (FGFR 1‑3). By blocking these pathways, it reduces fibroblast proliferation, angiogenesis, and extracellular matrix deposition, thereby limiting fibrotic tissue remodeling and tumor vascularisation.

Nintedanib is associated with a range of adverse reactions that vary in frequency and severity.

Common Side Effects

• Diarrhoea: frequent, often mild to moderate in intensity.
• Nausea: may occur with or without vomiting.
• Vomiting: occasional, usually self‑limiting.
• Abdominal pain: mild discomfort reported by some patients.
• Decreased appetite: reduced food intake leading to possible weight loss.
• Elevated liver enzymes: mild transaminase increases.

Serious or Rare Side Effects

• Hepatotoxicity: significant liver injury requiring monitoring.
• Bleeding events: increased risk of gastrointestinal or other bleeding.
• Cardiovascular events: rare cases of myocardial infarction or stroke.
• Severe infections: opportunistic infections in immunocompromised individuals.
• Gastrointestinal perforation: rare but potentially life‑threatening.
• Severe skin reactions: such as Stevens‑Johnson syndrome.

Before initiating therapy, clinicians should evaluate patient‑specific risk factors and monitor relevant parameters.

• Liver function monitoring: check transaminases and bilirubin before treatment and periodically thereafter.
• Bleeding risk assessment: avoid concurrent use with strong anticoagulants unless benefits outweigh risks.
• Cardiovascular evaluation: consider baseline cardiac status in patients with known disease.
• Pregnancy and lactation: use only if potential benefit justifies potential risk; safety data are limited.
• Hepatic impairment dosing: adjust dose in moderate to severe liver dysfunction.
• Store at below 25°C: keep in the original packaging, protect from moisture and direct sunlight.

Nintedanib may interact with other medicines that affect its metabolism or increase bleeding risk.

Major Interactions (Avoid)

• Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin): may raise nintedanib exposure.
• Potent P‑gp inhibitors (e.g., verapamil): can increase plasma concentrations.
• Anticoagulants and antiplatelet agents (e.g., warfarin, clopidogrel): heightened bleeding potential.

Moderate Interactions (Monitor Closely)

• Moderate CYP3A4 inhibitors (e.g., fluconazole): may modestly increase levels.
• CYP3A4 inducers (e.g., rifampicin, carbamazepine): may reduce efficacy.
• P‑gp inducers (e.g., phenytoin): could lower drug exposure.
• Non‑steroidal anti‑inflammatory drugs (NSAIDs): monitor for additive gastrointestinal bleeding risk.