Ofev (Nintedanib)
Tyrosine Kinase Inhibitor for Pulmonary Fibrosis
Quick Facts About Ofev
Key Takeaways About Ofev (Nintedanib)
- Slows lung fibrosis progression: Ofev reduces the annual decline in lung function (FVC) in patients with IPF, progressive fibrosing ILDs, and SSc-ILD
- Triple kinase inhibitor: Blocks VEGFR, FGFR, and PDGFR signalling pathways that drive fibroblast activity and scar tissue formation in the lungs
- Diarrhoea is very common: Occurs in more than 60% of IPF patients; manage with hydration, loperamide, and dose reduction if needed
- Contraindicated in pregnancy: Nintedanib can cause birth defects and must not be used during pregnancy; effective contraception is mandatory
- Monitor liver function: Liver enzyme elevations are common; liver tests should be performed before starting and regularly during treatment
What Is Ofev and What Is It Used For?
Ofev (nintedanib) is a tyrosine kinase inhibitor prescribed to slow the progression of lung scarring (fibrosis) in several conditions, including idiopathic pulmonary fibrosis (IPF), progressive fibrosing interstitial lung diseases, and systemic sclerosis-associated interstitial lung disease (SSc-ILD). It is also approved for fibrosing interstitial lung disease in children and adolescents aged 6 years and older.
Ofev belongs to a class of medicines known as tyrosine kinase inhibitors. It works by blocking three families of receptor tyrosine kinases – vascular endothelial growth factor receptors (VEGFR), fibroblast growth factor receptors (FGFR), and platelet-derived growth factor receptors (PDGFR). These receptors play central roles in the signalling pathways that drive the proliferation, migration, and differentiation of fibroblasts, the cells responsible for producing the excess scar tissue that characterises pulmonary fibrosis.
By inhibiting these pathways, Ofev slows the progressive scarring of lung tissue, helping to preserve lung function for longer. It is important to understand that Ofev does not reverse existing scarring – rather, it reduces the rate at which new scar tissue forms. Clinical trials have consistently demonstrated that nintedanib reduces the annual rate of decline in forced vital capacity (FVC), a key measure of lung function, across multiple forms of fibrosing lung disease.
Idiopathic Pulmonary Fibrosis (IPF)
Idiopathic pulmonary fibrosis is the most common and most severe form of idiopathic interstitial pneumonia. It is a chronic, progressive disease characterised by worsening scarring of the lung tissue, leading to irreversible loss of lung function, increasing breathlessness, and ultimately respiratory failure. The term "idiopathic" means the cause is unknown. IPF typically affects adults over the age of 50 and is more common in men than women.
The landmark INPULSIS trials (INPULSIS-1 and INPULSIS-2) demonstrated that nintedanib 150 mg twice daily significantly reduced the annual rate of FVC decline compared with placebo in patients with IPF. Based on these pivotal studies, Ofev received marketing authorisation from the European Medicines Agency (EMA) in 2015 and approval from the U.S. Food and Drug Administration (FDA) in 2014 for the treatment of IPF. The American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS), and Latin American Thoracic Association (ALAT) conditionally recommend nintedanib for IPF in their joint clinical practice guidelines.
Progressive Fibrosing Interstitial Lung Diseases
Many interstitial lung diseases other than IPF can develop a progressive fibrosing phenotype, meaning the scarring worsens over time despite standard treatment for the underlying condition. These progressive fibrosing ILDs include:
- Hypersensitivity pneumonitis – lung inflammation caused by inhaling certain dusts, moulds, or chemicals
- Autoimmune ILDs – including rheumatoid arthritis-associated ILD (RA-ILD) and mixed connective tissue disease-associated ILD
- Idiopathic non-specific interstitial pneumonia (NSIP) – a form of interstitial pneumonia with a more uniform inflammatory pattern
- Unclassifiable idiopathic interstitial pneumonia – cases that do not fit into a specific diagnostic category
- Other occupational and environmental lung diseases with a fibrosing course
The INBUILD trial demonstrated that nintedanib significantly reduced the rate of FVC decline in patients with a range of progressive fibrosing ILDs other than IPF. This led to an expanded indication for Ofev, making it the first approved treatment for chronic fibrosing ILDs with a progressive phenotype regardless of the underlying diagnosis.
Systemic Sclerosis-Associated ILD (SSc-ILD)
Systemic sclerosis (scleroderma) is an autoimmune connective tissue disease that can affect the skin, blood vessels, and internal organs. Interstitial lung disease is a common and serious complication of systemic sclerosis, occurring in up to 80% of patients. SSc-ILD is a leading cause of death in patients with systemic sclerosis.
The SENSCIS trial showed that nintedanib reduced the annual rate of FVC decline in patients with SSc-ILD compared with placebo. Based on these results, Ofev was approved for the treatment of SSc-ILD in adults by both the EMA and FDA. It can be used in combination with other treatments for systemic sclerosis, such as mycophenolate mofetil.
Paediatric Fibrosing ILD
Ofev is also approved for the treatment of fibrosing interstitial lung disease in children and adolescents aged 6 years and older. While fibrosing ILD is rare in children, it can lead to significant morbidity. The paediatric indication is based on extrapolation of efficacy from adult data, supported by pharmacokinetic studies in the paediatric population. Dosing is weight-based to ensure appropriate drug exposure in younger patients.
Nintedanib was originally developed by Boehringer Ingelheim and is also marketed under the brand name Vargatef for the treatment of certain types of lung cancer (non-small cell lung cancer). For pulmonary fibrosis indications, the brand name Ofev is used. The medicine is included in international treatment guidelines for IPF as one of only two approved antifibrotic therapies, alongside pirfenidone.
What Should You Know Before Taking Ofev?
Before starting Ofev, inform your doctor about all your medical conditions, especially liver problems, kidney disease, bleeding disorders, heart disease, and any planned surgery. Ofev is strictly contraindicated during pregnancy due to the risk of birth defects. Patients allergic to peanuts or soy must not take Ofev as the capsules contain soy lecithin.
Contraindications
You should not take Ofev if any of the following apply to you:
- Pregnancy – nintedanib has been shown to cause birth defects and embryo-foetal death in animal studies. Women of childbearing potential must use effective contraception during treatment and for at least 3 months after the last dose
- Allergy to nintedanib or any of the other ingredients in the capsules
- Allergy to peanuts or soy – Ofev capsules contain soy lecithin (E322), which may cause allergic reactions in people with peanut or soy allergy
Warnings and Precautions
Talk to your doctor or pharmacist before taking Ofev if you have or have had any of the following conditions:
- Liver problems – nintedanib is primarily eliminated through the liver. Patients with moderate or severe hepatic impairment (Child-Pugh B or C) should not take Ofev. Liver function tests (ALT, AST, bilirubin) must be monitored before starting treatment, monthly for the first 3 months, and periodically thereafter. Treatment should be interrupted or discontinued if liver enzyme levels rise significantly
- Kidney problems – patients with severe renal impairment (creatinine clearance less than 30 mL/min) have not been adequately studied. Cases of proteinuria (protein in the urine) and nephrotic syndrome have been reported
- Bleeding disorders or risk of bleeding – nintedanib inhibits VEGFR, which is involved in blood vessel maintenance. Patients on anticoagulants (such as warfarin or heparin) or with known bleeding risk should be closely monitored
- Heart problems – particularly if you have had a recent myocardial infarction (heart attack). Cases of myocardial infarction and arterial thromboembolic events have been reported during nintedanib treatment
- Recent surgery or planned surgery – nintedanib may impair wound healing due to its mechanism of action. Consider interrupting treatment before major surgery and restarting based on clinical assessment of wound healing
- Hypertension – blood pressure should be monitored and controlled during treatment, as nintedanib may increase blood pressure
- Pulmonary hypertension – use with caution, as this condition has not been adequately studied in clinical trials
- History of aneurysm or arterial dissection – VEGFR inhibitors may promote the formation or worsening of aneurysms and/or arterial dissections
- Risk of gastrointestinal (GI) perforation – nintedanib may increase the risk of GI perforation, particularly in patients also taking NSAIDs, corticosteroids, or with a history of abdominal surgery, diverticular disease, or peptic ulcers
- Thrombotic microangiopathy (TMA) – cases of TMA, including thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome, have been reported with VEGFR inhibitors
- Posterior reversible encephalopathy syndrome (PRES) – a rare neurological condition characterised by headache, seizures, confusion, and visual disturbances. If PRES is suspected, treatment should be discontinued
Drug Interactions
Nintedanib is a substrate of P-glycoprotein (P-gp). Co-administration with P-gp inhibitors can increase nintedanib blood levels, while P-gp inducers can decrease them. Nintedanib is also metabolised to a small extent by CYP3A4. The following table summarises the most clinically important drug interactions.
| Drug | Category | Effect | Recommendation |
|---|---|---|---|
| Ketoconazole | Antifungal (P-gp inhibitor) | Increases nintedanib blood levels by approximately 60% | Monitor closely for side effects; consider dose reduction to 100 mg BID |
| Erythromycin | Macrolide antibiotic (P-gp inhibitor) | Increases nintedanib blood levels | Monitor for increased side effects during concurrent use |
| Cyclosporine | Immunosuppressant (P-gp inhibitor) | Increases nintedanib blood levels | Monitor closely; dose adjustment may be needed |
| Rifampicin | Antibiotic for TB (P-gp inducer) | Decreases nintedanib blood levels by approximately 50% | Avoid concurrent use if possible; alternative antibiotics should be considered |
| Carbamazepine | Anticonvulsant (P-gp/CYP3A4 inducer) | Decreases nintedanib blood levels significantly | Avoid concurrent use; choose alternative anticonvulsant if possible |
| Phenytoin | Anticonvulsant (P-gp/CYP3A4 inducer) | Decreases nintedanib blood levels significantly | Avoid concurrent use; choose alternative anticonvulsant if possible |
| St. John's Wort (Hypericum perforatum) | Herbal supplement (P-gp inducer) | Decreases nintedanib blood levels | Avoid concurrent use |
| Pirfenidone | Antifibrotic | Increased risk of GI side effects (diarrhoea, nausea) and liver enzyme elevation | Use with caution; monitor liver function more frequently |
Pregnancy and Breastfeeding
Ofev must not be taken during pregnancy. Animal studies have shown that nintedanib causes serious harm to the developing foetus, including skeletal malformations and embryo-foetal death. Before starting treatment, a pregnancy test must be performed to rule out existing pregnancy. Women of childbearing potential must use highly effective contraception during treatment and for at least 3 months after the last dose. If you become pregnant while taking Ofev, contact your doctor immediately.
It is not known whether nintedanib or its metabolites are excreted in human breast milk. Because of the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during treatment with Ofev and for at least 3 months after the last dose. Discuss the risks and benefits with your doctor.
Ofev can cause birth defects. You must not become pregnant while taking this medicine. Use effective contraception during treatment and for at least 3 months after the last dose. If you think you may be pregnant, stop taking Ofev and contact your doctor immediately.
What Is the Correct Dosage of Ofev?
The recommended adult dose of Ofev is 150 mg twice daily, taken approximately 12 hours apart with food. If side effects are not tolerable, the dose may be reduced to 100 mg twice daily. Swallow the capsules whole with water – do not chew, crush, or open them. For children and adolescents, dosing is based on body weight.
Always take Ofev exactly as your doctor has told you. Do not change your dose without consulting your doctor first. The capsules should be swallowed whole with water and taken with food to reduce the risk of gastrointestinal side effects, particularly nausea and diarrhoea. Try to take each dose approximately 12 hours apart – for example, one capsule with breakfast and one with dinner.
Adults
IPF, Progressive Fibrosing ILD, and SSc-ILD
Recommended dose: 150 mg twice daily (taken approximately 12 hours apart)
Reduced dose: 100 mg twice daily (if side effects are intolerable at the full dose)
Your doctor may temporarily reduce the dose to 100 mg twice daily to manage side effects such as diarrhoea, nausea, or elevated liver enzymes. Once side effects have resolved, the dose may be increased back to 150 mg twice daily. If side effects persist at 100 mg twice daily, your doctor may consider discontinuing treatment.
Children and Adolescents (6–17 years)
For paediatric patients, the dose of Ofev is based on body weight. The aim is to achieve drug exposure similar to that in adults receiving 150 mg twice daily. The following table shows the recommended weight-based dosing.
| Body Weight | Single Dose | Capsules Per Dose | Frequency |
|---|---|---|---|
| 13.5–22.9 kg | 50 mg | 2 × 25 mg capsules | Twice daily |
| 23.0–33.4 kg | 75 mg | 3 × 25 mg capsules | Twice daily |
| 33.5–57.4 kg | 100 mg | 1 × 100 mg capsule | Twice daily |
| ≥57.5 kg | 150 mg | 1 × 150 mg capsule | Twice daily |
For children who have difficulty swallowing capsules, Ofev capsules may be taken with soft food. Open the capsule and empty the contents onto a spoonful of apple puree (applesauce). The mixture should be swallowed immediately and followed with a glass of water. Do not store the mixture for later use.
Missed Dose
If you forget a dose of Ofev, skip the missed dose and take your next dose at the usual time. Do not take a double dose to make up for the one you missed. If you are unsure what to do, contact your doctor or pharmacist.
Overdose
If you take more Ofev than you should, contact your doctor immediately or go to the nearest emergency department. Symptoms of overdose may include severe diarrhoea, nausea, vomiting, and abdominal pain. There is no specific antidote for nintedanib overdose. Treatment is supportive and symptomatic.
Always take Ofev capsules with food to improve absorption and reduce gastrointestinal side effects. Taking the capsules on an empty stomach may worsen nausea and diarrhoea. If you experience persistent nausea, try eating a small meal or snack before taking your capsule. Avoid high-fat meals if they exacerbate GI symptoms.
What Are the Side Effects of Ofev?
The most common side effects of Ofev are gastrointestinal: diarrhoea (which affects more than 6 in 10 IPF patients), nausea, abdominal pain, and elevated liver function tests. Other common side effects include vomiting, decreased appetite, weight loss, bleeding, rash, and headache. Diarrhoea is usually manageable with adequate hydration and anti-diarrhoeal medication.
Like all medicines, Ofev can cause side effects, although not everybody gets them. The type and frequency of side effects may differ depending on the underlying condition being treated. The following sections describe side effects reported in clinical trials for IPF and SSc-ILD.
Side Effects in Idiopathic Pulmonary Fibrosis (IPF)
Very Common
May affect more than 1 in 10 people
- Diarrhoea (reported in approximately 62% of patients)
- Nausea
- Abdominal pain (including upper abdominal pain)
- Abnormal liver function tests (elevated ALT, AST, alkaline phosphatase, gamma-GT)
Common
May affect up to 1 in 10 people
- Vomiting
- Decreased appetite
- Weight loss
- Bleeding (including epistaxis, bruising, haematuria)
- Rash (including erythematous and acneiform rash)
- Headache
Uncommon
May affect up to 1 in 100 people
- Pancreatitis
- Colitis (including microscopic colitis and ischaemic colitis)
- Drug-induced liver injury (serious hepatotoxicity)
- Thrombocytopenia (low platelet count)
- Hypertension (high blood pressure)
- Jaundice (yellowing of the skin and eyes)
- Pruritus (itching)
- Myocardial infarction (heart attack)
- Alopecia (hair loss)
- Proteinuria (protein in the urine)
Rare / Unknown Frequency
Reported from post-marketing experience
- Renal failure
- Aneurysm and arterial dissection
- Posterior reversible encephalopathy syndrome (PRES)
- Gastrointestinal perforation
- Thrombotic microangiopathy
Diarrhoea is the most frequent side effect of Ofev and can be severe in some patients. To manage diarrhoea effectively:
- Stay well hydrated – drink plenty of water and oral rehydration solutions
- Start anti-diarrhoeal treatment promptly – loperamide (Imodium) can be used at the first signs of diarrhoea
- Inform your doctor if diarrhoea is severe or persistent – dose reduction from 150 mg to 100 mg twice daily may be needed
- Avoid dehydration – seek medical attention if you cannot keep fluids down or experience signs of dehydration (dark urine, dizziness, dry mouth)
- Take Ofev with food – this may reduce gastrointestinal side effects
Side Effects in Systemic Sclerosis-Associated ILD (SSc-ILD)
The side effect profile in SSc-ILD patients is generally similar to that in IPF, but with some differences in frequency. In the SENSCIS trial, the most commonly reported side effects in nintedanib-treated SSc-ILD patients were:
- Diarrhoea – reported in approximately 76% of patients (higher than in IPF)
- Nausea – approximately 32%
- Vomiting – approximately 25%
- Abdominal pain – approximately 18%
- Skin ulcers – more common in SSc-ILD than IPF due to underlying disease
- Liver enzyme elevation – approximately 4.9%
If you experience any side effects not listed here, or if any side effect becomes severe, contact your doctor or pharmacist. You can also report side effects directly to your national medicines regulatory authority to help with ongoing safety monitoring.
How Should You Store Ofev?
Store Ofev capsules below 25°C. Keep the capsules in the original blister packaging or container to protect from moisture. Do not use after the expiry date. Keep out of the reach and sight of children.
Ofev soft capsules are sensitive to moisture. Always store the capsules in their original blister pack or container and keep the container tightly closed. Do not remove capsules from the blister pack until you are ready to take them. Check the expiry date (marked "EXP") on the packaging before use.
Do not throw away any unused or expired capsules in household waste or flush them down the toilet. Return unused medicines to your pharmacy for safe disposal. This helps protect the environment from pharmaceutical contamination.
What Does Ofev Contain?
Each Ofev capsule contains the active ingredient nintedanib (as nintedanib esilate) in strengths of 25 mg, 100 mg, or 150 mg. The capsules also contain inactive ingredients including soy lecithin. Patients with peanut or soy allergy must not take Ofev.
Active Ingredient
The active substance is nintedanib. Each soft capsule contains either 25 mg, 100 mg, or 150 mg of nintedanib (as nintedanib esilate). Nintedanib esilate is the salt form used to ensure adequate stability and absorption.
Inactive Ingredients (Excipients)
The capsule fill contains: medium-chain triglycerides, hard fat, and soy lecithin (E322).
The capsule shell contains: gelatin, glycerol (85%), titanium dioxide (E171), red iron oxide (E172), and yellow iron oxide (E172). The printing ink contains shellac, black iron oxide (E172), and propylene glycol.
Ofev capsules contain soy lecithin (E322). If you are allergic to peanuts or soy, you must not take this medicine. Soy lecithin is derived from soybean oil and may contain soy protein residues that can trigger allergic reactions in sensitised individuals. Inform your doctor and pharmacist about any known food allergies before starting treatment.
Capsule Appearance
25 mg capsules: Small, peach-coloured, oblong soft gelatin capsules.
100 mg capsules: Peach-coloured, oblong soft gelatin capsules imprinted with the Boehringer Ingelheim logo and "100".
150 mg capsules: Brown, oblong soft gelatin capsules imprinted with the Boehringer Ingelheim logo and "150".
Ofev is available in blister packs of 60 capsules (for the 100 mg and 150 mg strengths) and 120 capsules (for the 25 mg strength), corresponding to a 30-day supply.
Frequently Asked Questions About Ofev
Ofev (nintedanib) is used to treat idiopathic pulmonary fibrosis (IPF), progressive fibrosing interstitial lung diseases (ILDs), and systemic sclerosis-associated interstitial lung disease (SSc-ILD) in adults. It is also approved for fibrosing interstitial lung disease in children and adolescents aged 6 years and older. Ofev slows the progression of lung scarring by blocking three tyrosine kinase signalling pathways (VEGFR, FGFR, PDGFR) involved in fibrosis.
The most common side effects of Ofev are diarrhoea (affects more than 6 in 10 IPF patients), nausea, abdominal pain, and abnormal liver function tests. Other common side effects include vomiting, decreased appetite, weight loss, bleeding, rash, and headache. Diarrhoea is the most frequently reported side effect and can often be managed with adequate hydration, dose reduction, and anti-diarrhoeal medication such as loperamide.
Some patients may be prescribed both Ofev (nintedanib) and pirfenidone together for pulmonary fibrosis. However, combining these two antifibrotic medicines may increase the risk of gastrointestinal side effects such as diarrhoea, nausea, and vomiting, as well as elevated liver enzymes. If your doctor prescribes both, your liver function will be monitored more closely. Always consult your doctor before combining these medications.
Ofev capsules should be taken with food and swallowed whole with water. Do not chew, crush, or open the capsules. The standard adult dose is 150 mg twice daily, taken approximately 12 hours apart (for example, with breakfast and dinner). If you have difficulty swallowing capsules, you may take them with soft foods such as apple puree or applesauce. If you miss a dose, skip it and take the next dose at the usual time – do not take a double dose.
No. Ofev (nintedanib) must not be taken during pregnancy. Animal studies have shown that nintedanib causes harm to the developing foetus, including skeletal malformations and embryo-foetal death. Women of childbearing potential must use effective contraception during treatment and for at least 3 months after the last dose. A pregnancy test should be performed before starting treatment. If you become pregnant while taking Ofev, contact your doctor immediately.
Ofev (nintedanib) works by blocking three families of receptor tyrosine kinases: VEGFR (vascular endothelial growth factor receptors), FGFR (fibroblast growth factor receptors), and PDGFR (platelet-derived growth factor receptors). These receptors drive the proliferation, migration, and transformation of fibroblasts – the cells responsible for producing scar tissue in the lungs. By inhibiting these pathways, Ofev slows the decline in lung function and reduces the progression of fibrosis. It does not reverse existing scarring, but it significantly reduces the rate at which new scar tissue forms.
References
This article is based on the following international medical guidelines and peer-reviewed sources. All medical claims have evidence level 1A, the highest quality of evidence based on systematic reviews of randomised controlled trials.
- Richeldi L, du Bois RM, Raghu G, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis (INPULSIS trials). New England Journal of Medicine. 2014;370(22):2071–2082. doi:10.1056/NEJMoa1402584
- Flaherty KR, Wells AU, Cottin V, et al. Nintedanib in progressive fibrosing interstitial lung diseases (INBUILD trial). New England Journal of Medicine. 2019;381(18):1718–1727. doi:10.1056/NEJMoa1908681
- Distler O, Highland KB, Gahlemann M, et al. Nintedanib for systemic sclerosis-associated interstitial lung disease (SENSCIS trial). New England Journal of Medicine. 2019;380(26):2518–2528. doi:10.1056/NEJMoa1903076
- Raghu G, Remy-Jardin M, Richeldi L, et al. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. American Journal of Respiratory and Critical Care Medicine. 2022;205(9):e18–e47.
- European Medicines Agency (EMA). Ofev (nintedanib) – Summary of Product Characteristics. EMA product information database. Accessed February 2026.
- U.S. Food and Drug Administration (FDA). Ofev (nintedanib) capsules – Prescribing Information. FDA Drugs@FDA database. Accessed February 2026.
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd list. Geneva: WHO; 2023.
- British National Formulary (BNF). Nintedanib. NICE BNF monograph. Accessed February 2026.
- National Institute for Health and Care Excellence (NICE). Nintedanib for treating idiopathic pulmonary fibrosis. Technology appraisal guidance [TA379]. 2016.
Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, a group of licensed specialist physicians with expertise in pulmonology, clinical pharmacology, and internal medicine.
Medical Writers
Board-certified physicians specialising in respiratory medicine and clinical pharmacology with documented academic and clinical experience.
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