Nintedanib Ratiopharm (Nintedanib)

Nintedanib is an antifibrotic and antineoplastic agent that targets multiple tyrosine‑kinase pathways involved in fibrosis and tumor angiogenesis.

• Idiopathic pulmonary fibrosis: slows decline in lung function and reduces disease progression.
• Systemic sclerosis‑associated interstitial lung disease: improves forced vital capacity and delays worsening of lung fibrosis.
• Non‑small cell lung cancer (in combination therapy): enhances efficacy of chemotherapy regimens and may improve progression‑free survival.

• Nintedanib blocks the intracellular kinase activity of several receptor tyrosine kinases, notably VEGFR‑1/2/3, PDGFR‑α/β and FGFR‑1/2/3. Inhibition of these receptors curtails endothelial cell proliferation, fibroblast activation, and extracellular matrix deposition, thereby limiting angiogenesis and fibrotic remodeling in lung tissue and tumours.

Nintedanib may cause a range of adverse reactions, which are categorized by frequency and severity.

Common Side Effects

• Nausea: mild to moderate upset stomach.
• Diarrhoea: frequent loose stools, often manageable with hydration.
• Abdominal pain: cramping or discomfort in the stomach area.
• Decreased appetite: reduced desire to eat.
• Vomiting: occasional episodes of expulsion of stomach contents.

Serious or Rare Side Effects

• Elevated liver enzymes: potential indication of hepatic injury.
• Arterial thromboembolic events: risk of blood clots in arteries.
• Severe bleeding: increased susceptibility to gastrointestinal or other bleeding.
• Gastrointestinal perforation: rare but serious tearing of the GI tract.

Before initiating therapy, clinicians should consider several safety aspects.

• Renal function: assess baseline and monitor during treatment.
• Hepatic function: avoid in patients with severe hepatic impairment; monitor liver enzymes regularly.
• Bleeding risk: use caution in patients receiving anticoagulants or antiplatelet agents.
• Pregnancy and lactation: safety not established; avoid use in pregnant or nursing women.
• Drug interactions: review concomitant medications for CYP3A4 substrates or inhibitors.
• Store at ambient temperature: keep below 25 °C, retain original packaging, protect from moisture.

Nintedanib may interact with other medicines, requiring careful management.

Major Interactions (Avoid)

• Strong CYP3A4 inducers (e.g., rifampicin, carbamazepine): markedly reduce nintedanib exposure.
• Anticoagulants (e.g., warfarin, direct oral anticoagulants): increase risk of serious bleeding.
• Concurrent VEGF inhibitors: additive toxicity, especially hypertension and proteinuria.

Moderate Interactions (Monitor Closely)

• Moderate CYP3A4 inhibitors (e.g., ketoconazole, erythromycin): may raise nintedanib plasma levels.
• P‑glycoprotein inhibitors (e.g., verapamil): can increase systemic exposure.
• Diuretics: may exacerbate dehydration from gastrointestinal losses, requiring fluid monitoring.