Nintedanib
💊 Nintedanib (Ofev®)
🫁 Nintedanib is an anti-fibrotic tyrosine kinase inhibitor used in fibrosing interstitial lung diseases to slow the rate of lung function decline (it is not a “quick symptomatic” drug).
Because adverse effects are common (especially diarrhoea and LFT rise), good counselling + early dose adjustment massively improves adherence and outcomes.
ℹ️ What is it?
- 🧬 Oral small-molecule tyrosine kinase inhibitor with anti-fibrotic and anti-proliferative effects.
- 🎯 Inhibits signalling pathways including receptors for VEGF, FGF, and PDGF → reduces fibroblast activation, migration, and extracellular matrix deposition.
- 📉 Clinical effect: slows FVC decline (disease modification), rather than reversing established fibrosis.
✅ Indications (UK practice)
- 🫁 Idiopathic Pulmonary Fibrosis (IPF) (per NICE commissioning criteria).
- 🫁 Progressive fibrosing interstitial lung diseases (PF-ILD) (non-IPF fibrosing ILDs with progression despite standard care, per NICE criteria).
- 🧑⚕️ Systemic sclerosis–associated ILD (SSc-ILD): licensed, but NHS access/commissioning may depend on local formulary/region—follow ILD MDT and local pathway.
📦 Formulation
- 💊 Soft capsules: 100 mg and 150 mg.
- 🍽️ Take with food and swallow whole with water (do not chew/crush).
🧾 Dosing
- 🟩 Standard adult dose: 150 mg twice daily (approximately 12 hours apart).
- 🟧 If not tolerated: reduce to 100 mg twice daily.
- ⛔ If 100 mg BD not tolerated: stop (or prolonged interruption per specialist advice).
- ❌ Missed dose: do not double; take next dose at the scheduled time.
🧠 Dose adjustment & special populations
- 🟧 Mild hepatic impairment (Child-Pugh A): start/maintain at 100 mg twice daily.
- ⛔ Moderate/severe hepatic impairment (Child-Pugh B/C): generally not recommended.
- 🚰 Renal impairment: no routine adjustment for mild–moderate; severe renal impairment has limited data—specialist decision.
- 👶 Pregnancy: avoid (see counselling below).
⚠️ Contraindications / caution zones
- 🧪 Significant baseline liver disease or markedly abnormal transaminases (specialist decision; monitor closely).
- 🩸 Bleeding risk (e.g., on anticoagulation, recent major bleed) — not an absolute ban, but needs explicit risk–benefit and monitoring.
- 🧠/💓 Prior arterial thrombotic events (MI, stroke) — caution and optimise CV prevention.
- 🏥 Peri-operative period: discuss with specialist team (theoretical wound-healing/bleeding considerations).
🔬 Baseline checks (before starting)
- 🧪 LFTs: ALT/AST, bilirubin, ALP ± albumin.
- 🩸 FBC (baseline), U&E, pregnancy test if relevant.
- 📈 Document baseline FVC, symptoms, oxygen requirement, exacerbation history (ILD clinic/MDT).
- 💊 Medication review for interactions (see below).
📅 Monitoring (pragmatic UK schedule)
- 🧪 LFTs: baseline, then monthly for 3 months, then every 3 months (and any time symptoms suggest liver injury).
- 🚽 Ask actively about diarrhoea at every contact (early treatment prevents dehydration/AKI and drug discontinuation).
- ⚖️ Weight trend (chronic diarrhoea/anorexia can lead to significant weight loss).
- 🫁 ILD follow-up: FVC trend + exacerbations + function (specialist clinic).
🤢 Common adverse effects (and what to do)
- 🚽 Diarrhoea (very common): start loperamide early, maintain hydration, consider dose reduction/interruption if persistent.
- 🤮 Nausea/vomiting, abdominal pain: take with food, consider antiemetic, review dose.
- 🧪 Raised ALT/AST: repeat LFTs, consider dose reduction/interruption; stop if severe or with jaundice.
- ⚠️ Reduced appetite/weight loss: dietitian input if needed; rule out dehydration and malabsorption.
🚨 Serious/less common adverse effects (red flags)
- 🟨 Drug-induced liver injury: jaundice, dark urine, RUQ pain, marked LFT rise → urgent review and stop pending specialist advice.
- 🩸 Bleeding (esp. GI): melaena/haematemesis/unexplained anaemia → urgent assessment.
- 🦵 Thromboembolism (DVT/PE symptoms) or arterial events (stroke/MI symptoms) → emergency pathway.
- 🧯 Severe diarrhoea with dehydration: risk of AKI/hypotension → treat promptly, consider admission if frail.
🔗 Drug interactions (high-yield)
- 🧬 Nintedanib is a substrate of P-gp (and affected by strong inhibitors/inducers).
- ⬆️ Strong P-gp/CYP3A4 inhibitors (e.g. some azoles/macrolides) may increase exposure → monitor tolerability/LFTs.
- ⬇️ Strong inducers (e.g. rifampicin, carbamazepine, phenytoin, St John’s wort) may reduce exposure → avoid where possible.
- 🩸 Anticoagulants/antiplatelets: bleeding risk may increase → monitor clinically (not automatically contraindicated).
🗣️ Patient counselling (copy-paste friendly)
- 🍽️ Take with food, 12 hours apart; swallow whole.
- 🚽 If diarrhoea starts: use loperamide early, drink more fluids, and contact the ILD team if persistent.
- 🧪 You will need regular blood tests (liver monitoring) especially early on.
- 🟨 Seek urgent help for jaundice, severe tummy pain, black stools/vomiting blood, chest pain, sudden breathlessness, one-sided weakness.
- 🤰 Avoid pregnancy; use effective contraception and discuss plans with the specialist team.
🏥 Practical UK workflow (how it usually runs)
- 🫁 Initiation is typically by Respiratory/ILD specialist (MDT diagnosis + criteria check).
- 📋 Baseline bloods + early LFT monitoring arranged via ILD clinic/shared care (varies by ICB).
- 📈 Primary care role often includes: supporting adherence, managing diarrhoea advice, checking blood results if shared care, and aggressive CV risk reduction.
📚 References
