Usage
Nintedanib is prescribed for the treatment of:
- Idiopathic Pulmonary Fibrosis (IPF): A chronic and progressive lung disease characterized by scarring and thickening of lung tissue.
- Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs): A group of lung disorders characterized by inflammation and scarring, leading to breathing difficulties. This includes conditions like unclassifiable ILDs, autoimmune ILDs (e.g., rheumatoid arthritis-associated ILD), chronic hypersensitivity pneumonitis, sarcoidosis, myositis, Sjögren syndrome, coal workers’ pneumoconiosis, and idiopathic forms of interstitial pneumonias (e.g., idiopathic nonspecific interstitial pneumonia).
- Systemic Sclerosis-associated Interstitial Lung Disease (SSc-ILD): A lung complication of systemic sclerosis (scleroderma), an autoimmune disease affecting connective tissues. Nintedanib helps slow the decline in lung function.
Pharmacological Classification: Nintedanib is a multiple tyrosine kinase inhibitor. Specifically, it targets vascular endothelial growth factor receptors (VEGFR 1-3), fibroblast growth factor receptors (FGFR 1-3), and platelet-derived growth factor receptors (PDGFR α and β).
Mechanism of Action: Nintedanib primarily works by inhibiting tyrosine kinases involved in pathways that promote fibrosis (scarring) and angiogenesis (formation of new blood vessels). By blocking these pathways, it aims to slow down the progression of fibrotic lung diseases.
Alternate Names
International Nonproprietary Name (INN): Nintedanib
Brand Names: Ofev
How It Works
Pharmacodynamics: Nintedanib exerts its therapeutic effect by inhibiting key tyrosine kinases (VEGFR, FGFR, PDGFR) involved in the pathogenesis of fibrotic lung diseases. These kinases play crucial roles in promoting fibroblast proliferation, differentiation into myofibroblasts, and excessive collagen deposition, which contribute to the scarring and stiffening of lung tissue.
Pharmacokinetics:
- Absorption: Nintedanib is well-absorbed orally, with peak plasma concentrations reached within 2 to 4 hours after administration. Food intake enhances absorption and is recommended.
- Distribution: Nintedanib is extensively distributed throughout the body, exhibiting a high volume of distribution. It is highly protein-bound (approximately 97.8%).
- Metabolism: Primarily metabolized in the liver, predominantly by CYP3A4, and by other CYP enzymes (CYP1A1, CYP1A2 and CYP2C19) to a minor extent and also through intestinal metabolism.
- Elimination: Nintedanib and its metabolites are mainly eliminated through biliary/fecal excretion (approximately 93% and 84% respectively), with a small portion eliminated in the urine (about 0.1%). The elimination half-life ranges from 10 to 15 hours.
- Receptor binding, enzyme inhibition, or neurotransmitter modulation: Nintedanib exerts its effects through the inhibition of tyrosine kinase activity, primarily VEGFR, FGFR, and PDGFR.
Dosage
Standard Dosage
Adults:
The standard dose is 150 mg twice daily, taken approximately 12 hours apart, with food.
Children:
Nintedanib is not recommended for use in children under 18 years of age. Safety and efficacy have not been established in this population.
Special Cases:
- Elderly Patients (≥65 years): No a priori dose adjustment is required. However, patients ≥75 years may be more likely to require a dose reduction due to increased risk of adverse effects. Close monitoring is recommended.
- Patients with Renal Impairment: No dose adjustment is necessary for mild to moderate renal impairment. Use in patients with severe renal impairment (creatinine clearance <30 mL/min) or end-stage renal disease has not been studied.
- Patients with Hepatic Dysfunction: For mild hepatic impairment (Child-Pugh A), the recommended dose is 100 mg twice daily. Nintedanib is not recommended for patients with moderate to severe hepatic impairment (Child-Pugh B or C).
- Patients with Comorbid Conditions: Caution should be exercised in patients with coronary artery disease, thromboembolic events, a history of gastrointestinal perforation, or those taking anticoagulant medications. Dose adjustments may be necessary.
Clinical Use Cases
Nintedanib is not indicated for use in clinical settings such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dose adjustments to 100 mg twice daily or temporary interruption of treatment may be required in patients experiencing adverse reactions, particularly gastrointestinal issues (diarrhea, nausea, vomiting) or elevated liver enzymes.
Side Effects
Common Side Effects:
Diarrhea, nausea, vomiting, abdominal pain, decreased appetite, weight loss, headache, and elevated liver enzymes.
Rare but Serious Side Effects:
Liver injury (hepatotoxicity), bleeding, arterial thromboembolic events (heart attack, stroke), gastrointestinal perforation, and renal impairment.
Long-Term Effects:
Chronic complications from prolonged use are still being investigated. Monitoring for liver function, renal function, and cardiovascular events is essential.
Adverse Drug Reactions (ADR):
Severe liver injury, gastrointestinal bleeding or perforation, and arterial thromboembolic events require immediate medical attention.
Contraindications
- Hypersensitivity to nintedanib, peanut, or soya.
- Pregnancy.
- Moderate to severe hepatic impairment (Child-Pugh B or C).
Drug Interactions
Nintedanib is primarily metabolized by CYP3A4 and is a substrate for P-glycoprotein (P-gp). Therefore, concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, erythromycin) or P-gp inhibitors (e.g., cyclosporine) may increase nintedanib plasma concentrations. Conversely, strong CYP3A4 inducers (e.g., rifampicin, carbamazepine, phenytoin, St. John’s wort) or P-gp inducers may decrease nintedanib levels, potentially reducing efficacy. Caution is advised with concomitant use of anticoagulants and antiplatelet agents due to an increased risk of bleeding.
Pregnancy and Breastfeeding
Pregnancy: Nintedanib is contraindicated during pregnancy (Pregnancy Category D) due to the risk of fetal harm and birth defects. Effective contraception is essential during treatment and for at least 3 months after the last dose.
Breastfeeding: Breastfeeding is not recommended while taking nintedanib as the drug may be excreted in breast milk and could potentially harm the nursing infant.
Drug Profile Summary
- Mechanism of Action: Tyrosine kinase inhibitor targeting VEGFR, FGFR, and PDGFR, reducing fibrosis and angiogenesis.
- Side Effects: Diarrhea, nausea, vomiting, liver enzyme elevation, bleeding risk, gastrointestinal perforation.
- Contraindications: Pregnancy, moderate/severe hepatic impairment, hypersensitivity.
- Drug Interactions: CYP3A4 and P-gp inhibitors/inducers, anticoagulants, antiplatelet agents.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy; breastfeeding not recommended.
- Dosage: 150 mg twice daily (with food); adjustments for hepatic impairment and adverse events.
- Monitoring Parameters: Liver function tests, renal function, blood pressure, signs of bleeding.
Popular Combinations
No specific drug combinations with nintedanib are routinely recommended.
Precautions
Screen for pre-existing liver disease, renal dysfunction, and cardiovascular disease. Counsel patients regarding potential side effects, drug interactions, and the importance of contraception. Monitor liver function tests regularly. Patients should avoid smoking.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Nintedanib?
A: The recommended dose is 150 mg twice daily (approximately 12 hours apart) taken with food. The dose may be reduced to 100 mg twice daily for patients with mild hepatic impairment or those who experience adverse reactions.
Q2: What are the most common side effects?
A: Diarrhea, nausea, vomiting, and abdominal pain are among the most common side effects.
Q3: How does Nintedanib work?
A: Nintedanib inhibits tyrosine kinases involved in fibrosis and angiogenesis, thus slowing the progression of fibrotic lung diseases.
Q4: Can Nintedanib be used during pregnancy?
A: No, Nintedanib is contraindicated during pregnancy due to the risk of fetal harm.
Q5: Are there any drug interactions I should be aware of?
A: Yes, Nintedanib can interact with drugs that are strong CYP3A4 and P-gp inhibitors or inducers. Also, co-administration with anticoagulants increases the risk of bleeding.
Q6: What should I monitor in patients taking Nintedanib?
A: Monitor liver function tests, renal function, signs and symptoms of bleeding, and cardiovascular events.
Q7: Can Nintedanib be crushed or chewed?
A: No, Nintedanib capsules should be swallowed whole with food and water. They should not be chewed, crushed, or opened.
Q8: What should I do if a patient misses a dose?
A: If a dose is missed, the patient should take the next dose at the usual scheduled time. They should not double the dose.
Q9: What is the difference between the 100mg and 150mg doses?
A: The 150 mg dose is the standard recommended dose. The 100 mg dose is typically used for patients with mild hepatic impairment or for dose adjustments due to adverse reactions.
Please note that this information is current as of February 16, 2025, and might change with time. Always refer to the latest prescribing information.
