Nintedanib Zentiva
Generic tyrosine kinase inhibitor for idiopathic pulmonary fibrosis and progressive fibrosing interstitial lung diseases
Quick Facts About Nintedanib Zentiva
Key Takeaways About Nintedanib Zentiva
- Bioequivalent generic of Ofev: Nintedanib Zentiva contains the identical active substance, nintedanib esylate, as the originator medicine Ofev and is approved under European generic medicines regulations with the same clinical indications and safety profile.
- Slows disease progression: Nintedanib reduces the annual rate of forced vital capacity (FVC) decline by approximately 50% in patients with idiopathic pulmonary fibrosis, as demonstrated in the INPULSIS-1 and INPULSIS-2 phase III trials.
- Triple kinase inhibitor: It simultaneously targets VEGFR, FGFR, and PDGFR receptor families to block the fibroblast-driven scarring process in the lungs, providing a multi-pathway antifibrotic effect.
- Diarrhea is the most common side effect: Occurring in over 60% of patients, it can usually be managed with anti-diarrheal medicines such as loperamide, adequate hydration, and dose adjustment from 150 mg to 100 mg twice daily if needed.
- Liver monitoring and pregnancy prevention are essential: Liver function tests (ALT, AST, bilirubin) must be checked before starting treatment and at regular intervals, and women of childbearing potential must use highly effective contraception during and for at least 3 months after treatment.
What Is Nintedanib Zentiva and What Is It Used For?
Nintedanib Zentiva is a generic tyrosine kinase inhibitor that slows the progression of pulmonary fibrosis by blocking the signalling pathways responsible for abnormal scar tissue formation in the lungs. It is approved for idiopathic pulmonary fibrosis (IPF), systemic sclerosis-associated interstitial lung disease (SSc-ILD), and other chronic fibrosing interstitial lung diseases with a progressive phenotype.
Nintedanib Zentiva contains the active substance nintedanib (administered as the esylate salt), a small molecule belonging to the class of tyrosine kinase inhibitors. The medicine was developed as an antifibrotic agent specifically targeting the molecular pathways responsible for the progressive scarring (fibrosis) that characterises several serious chronic lung diseases. It is supplied as soft gelatin capsules for oral administration in a strength of 100 mg and is manufactured by Zentiva as a generic equivalent of the originator product Ofev (Boehringer Ingelheim). Being a generic medicine, Nintedanib Zentiva is regulated to deliver the same plasma concentrations and therapeutic effect as the reference product.
Pulmonary fibrosis encompasses a heterogeneous group of lung diseases characterised by progressive scarring of the lung interstitium, which gradually stiffens the lung tissue and causes an irreversible decline in lung function. In idiopathic pulmonary fibrosis (IPF) — the most common and severe form — the cause of the scarring is unknown. IPF typically affects adults over the age of 50, shows a male predominance, and carries a median survival of only 3 to 5 years from diagnosis in untreated patients. The hallmark symptoms are progressive exertional breathlessness and a persistent dry cough, while high-resolution CT imaging typically reveals a usual interstitial pneumonia (UIP) pattern with bibasilar reticulation, traction bronchiectasis, and subpleural honeycombing.
Nintedanib works by competitively binding to the adenosine triphosphate (ATP) binding pocket of three receptor tyrosine kinase families that play central roles in fibrogenesis: vascular endothelial growth factor receptors (VEGFR 1, 2, and 3), fibroblast growth factor receptors (FGFR 1, 2, and 3), and platelet-derived growth factor receptors (PDGFR alpha and beta). By inhibiting signalling through these receptors, nintedanib reduces the proliferation, migration, and transformation of fibroblasts into myofibroblasts — the key effector cells responsible for excessive collagen deposition and extracellular matrix remodelling in fibrotic lungs. This multi-targeted mechanism is thought to provide broader antifibrotic activity than strategies targeting a single pathway.
The clinical efficacy of nintedanib in IPF was established in three pivotal randomised controlled trials. The phase II TOMORROW trial first demonstrated a clinically meaningful reduction in the annual rate of forced vital capacity (FVC) decline at the 150 mg twice-daily dose. These findings were confirmed in the two replicate INPULSIS phase III trials, published together in the New England Journal of Medicine in 2014. Across these studies, nintedanib consistently reduced the annual rate of FVC decline by approximately 50% compared with placebo. Long-term safety and tolerability were later confirmed in the INPULSIS-ON open-label extension. Additional efficacy for systemic sclerosis-associated ILD and for progressive fibrosing ILD was demonstrated in the SENSCIS (2019) and INBUILD (2019) trials, respectively, extending the clinical utility of nintedanib beyond IPF.
Approved Indications
Nintedanib Zentiva is approved for the following conditions in adults:
- Idiopathic Pulmonary Fibrosis (IPF): The primary indication. Nintedanib slows disease progression by reducing the annual rate of lung function decline and is recommended as a conditional treatment option in the 2022 ATS/ERS/JRS/ALAT Clinical Practice Guideline for IPF, alongside pirfenidone.
- Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD): Based on the SENSCIS trial, nintedanib reduces the annual rate of FVC decline in patients with this serious pulmonary complication of systemic sclerosis (scleroderma) and may be combined with background immunosuppressive therapy such as mycophenolate mofetil.
- Chronic Fibrosing Interstitial Lung Diseases with a Progressive Phenotype: Based on the INBUILD trial, nintedanib is indicated for patients whose non-IPF chronic fibrosing ILD (e.g., hypersensitivity pneumonitis, sarcoidosis, connective-tissue-disease-associated ILD, idiopathic non-specific interstitial pneumonia) shows a progressive phenotype despite standard management.
Nintedanib Zentiva does not cure pulmonary fibrosis. It is an antifibrotic therapy designed to slow disease progression and preserve lung function for as long as possible. Treatment should be initiated and supervised by a specialist physician experienced in the diagnosis and management of interstitial lung diseases, and should be integrated with non-pharmacological measures such as pulmonary rehabilitation, vaccinations, oxygen therapy when indicated, and, where appropriate, referral for lung transplant assessment.
What Should You Know Before Taking Nintedanib Zentiva?
Before starting Nintedanib Zentiva, your doctor will assess your liver function, bleeding risk, and cardiovascular status. The medication is contraindicated in patients with severe hepatic impairment and during pregnancy, and it requires careful evaluation of drug interactions and several pre-existing conditions.
Contraindications
Nintedanib Zentiva must not be used in the following situations:
- Hypersensitivity: Known allergy to nintedanib, peanut, soya, or any of the excipients in the formulation. The soft capsules contain soya lecithin as an emulsifier.
- Pregnancy: Nintedanib is contraindicated during pregnancy because of demonstrated embryo-fetal toxicity in preclinical studies. Women of childbearing potential must have a negative pregnancy test before initiation and must use highly effective contraception during treatment and for at least 3 months after the final dose.
- Severe hepatic impairment: Nintedanib is contraindicated in patients with severe hepatic impairment (Child-Pugh C), as the drug is extensively metabolised and exposure may be significantly increased, raising the risk of serious hepatotoxicity.
Warnings and Precautions
Your healthcare provider should be aware of and monitor for the following conditions and risks during treatment with Nintedanib Zentiva. Careful patient selection and active safety monitoring are central to the responsible use of this medicine.
Hepatotoxicity: Nintedanib can cause drug-induced liver injury, including elevations in hepatic transaminases (ALT, AST) and bilirubin. Cases of serious liver injury, including fatal outcomes, have been reported in post-marketing surveillance. Liver function tests should be performed before starting treatment, at regular intervals during the first three months, and periodically thereafter or as clinically indicated. If ALT or AST rises to more than 3 times the upper limit of normal (ULN), dose reduction from 150 mg to 100 mg twice daily or treatment interruption is recommended. If elevations exceed 5 times ULN or are accompanied by signs of liver damage (jaundice, elevated bilirubin), treatment should be permanently discontinued. Risk factors include Asian ethnicity and low body weight.
Diarrhea: Diarrhea is the most frequently reported adverse reaction and can be severe in a minority of patients. Patients should be advised to hydrate adequately and to contact their healthcare team promptly if diarrhea is persistent or worsening. Anti-diarrheal therapy (e.g., loperamide) should be started at the first signs of diarrhea together with dietary measures. If supportive care is insufficient, dose reduction from 150 mg to 100 mg twice daily is the next step. If severe diarrhea persists despite optimal supportive care and dose reduction, treatment discontinuation should be considered to avoid volume depletion and electrolyte disturbances.
Nausea and vomiting: These gastrointestinal adverse effects are common and may contribute to decreased appetite and weight loss over time. Anti-emetic therapy and nutritional support should be offered as needed, and body weight should be monitored regularly. Dose reduction may be required in severe cases.
Bleeding risk: Nintedanib inhibits VEGFR, which plays a role in vascular homeostasis. Treatment may therefore increase the risk of bleeding events such as nosebleeds, bruising, or gastrointestinal bleeding. Patients with a known predisposition to bleeding (including those on full-dose anticoagulant therapy) should be treated with caution. Nintedanib should only be used in these patients if the anticipated benefit outweighs the potential risk.
Arterial thromboembolic events: An increased incidence of myocardial infarction has been observed in some clinical studies. Patients with cardiovascular risk factors, including known coronary artery disease, uncontrolled hypertension, or prior stroke, should be monitored carefully during treatment. Treatment should be interrupted in patients who develop signs of acute myocardial ischemia.
Gastrointestinal perforation: Gastrointestinal perforation has been reported with nintedanib, including fatal cases. Particular caution should be exercised in patients with previous abdominal surgery, recent history of gastrointestinal perforation, peptic ulcer disease, diverticular disease, or concurrent use of corticosteroids or NSAIDs. Treatment should be permanently discontinued in patients who develop gastrointestinal perforation.
Renal impairment and proteinuria: Cases of renal impairment and proteinuria, including nephrotic syndrome, have been reported. Patients should be monitored for signs of renal dysfunction during treatment, and the benefit-risk balance should be reassessed if clinically significant renal impairment or proteinuria develops.
Liver function tests (ALT, AST, and bilirubin) must be performed before initiation of treatment, monthly for the first three months, and then periodically thereafter. Cases of severe drug-induced liver injury, including fatal cases, have been reported. Contact your doctor immediately if you experience unexplained fatigue, dark urine, jaundice (yellowing of the skin or eyes), pale stools, loss of appetite, or right upper abdominal pain.
Pregnancy and Breastfeeding
Pregnancy: Nintedanib Zentiva is contraindicated during pregnancy. Animal studies have demonstrated reproductive toxicity, including embryo-fetal lethality, structural abnormalities, and skeletal variations at exposures below the maximum recommended human dose. Women of childbearing potential must have a negative pregnancy test before treatment initiation and must use highly effective contraception during treatment and for at least 3 months after the final dose. If a patient becomes pregnant while taking nintedanib, treatment must be stopped immediately and the patient counselled about the potential hazards to the fetus.
Contraceptive considerations: The efficacy of oral hormonal contraceptives may be compromised by vomiting or severe diarrhea. Women relying on oral contraception while taking nintedanib are therefore advised to use an additional barrier method or consider a non-oral contraceptive option after discussion with their healthcare provider.
Breastfeeding: It is not known whether nintedanib or its metabolites are excreted in human breast milk. A risk to the breastfed infant cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue nintedanib therapy, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother.
Fertility: There are no clinical data on the effect of nintedanib on human fertility. Animal studies did not indicate direct harmful effects on fertility at the exposures studied, but the potential for impaired fertility in humans cannot be excluded based on the mechanism of action (VEGFR inhibition). Men planning to father children should discuss this with their doctor before starting treatment.
How Does Nintedanib Zentiva Interact with Other Drugs?
Nintedanib is a substrate of P-glycoprotein (P-gp) and, to a minor extent, CYP3A4. Co-administration with potent P-gp inhibitors can increase nintedanib exposure, while potent P-gp inducers can reduce its efficacy. Anticoagulants and antiplatelet agents may increase bleeding risk when used concurrently.
Understanding drug interactions is essential for the safe use of Nintedanib Zentiva. Nintedanib is primarily metabolised by hydrolytic ester cleavage to the free acid moiety BIBF 1202, followed by glucuronidation through UGT enzymes to produce BIBF 1202 glucuronide. CYP-dependent oxidation plays only a minor role in biotransformation. The clinically most relevant transporter for drug interactions is P-glycoprotein (P-gp), for which nintedanib, BIBF 1202, and BIBF 1202 glucuronide are all substrates. Modulation of P-gp activity can therefore meaningfully alter nintedanib exposure.
Before starting Nintedanib Zentiva, you should tell your doctor and pharmacist about all medicines you are taking, including prescription medicines, over-the-counter products, herbal remedies, and dietary supplements. The tables below summarise the most clinically relevant interactions. This list is not exhaustive, and your prescriber will assess your complete medication history.
Major Interactions
| Interacting Drug | Effect | Clinical Recommendation |
|---|---|---|
| Ketoconazole | Potent P-gp and CYP3A4 inhibitor. Increased nintedanib AUC by ~60% and Cmax by ~83% | Use with caution. Monitor for increased gastrointestinal and hepatic side effects. Consider dose reduction if poorly tolerated. |
| Erythromycin | Moderate P-gp and CYP3A4 inhibitor. Increased nintedanib AUC by ~61% and Cmax by ~36% | Use with caution. Monitor closely for adverse reactions, especially gastrointestinal effects. |
| Rifampicin | Potent P-gp and CYP3A4 inducer. Decreased nintedanib AUC by ~50% and Cmax by ~60% | Avoid co-administration. Significantly reduces antifibrotic efficacy. Select an alternative antibiotic where possible. |
| Carbamazepine | Potent P-gp and CYP3A4 inducer. Expected to significantly decrease nintedanib exposure | Avoid co-administration. Consider an alternative anti-epileptic without P-gp induction (e.g., levetiracetam). |
| Phenytoin | Potent CYP3A4 and P-gp inducer. Expected to reduce nintedanib plasma levels | Avoid co-administration. Select an alternative anti-epileptic medicine after neurologist consultation. |
| St. John's Wort (Hypericum perforatum) | Potent P-gp and CYP3A4 inducer. Expected to significantly reduce nintedanib exposure | Avoid concomitant use. Herbal supplements are not recommended with nintedanib — always disclose supplement use to your prescriber. |
Minor Interactions
| Interacting Drug | Effect | Clinical Recommendation |
|---|---|---|
| Warfarin and other anticoagulants | Nintedanib inhibits VEGFR, potentially increasing bleeding risk. Additive anticoagulant effect. | Monitor INR and signs of bleeding closely. Adjust anticoagulant dose as needed and discuss DOAC alternatives. |
| Antiplatelet agents (aspirin, clopidogrel) | Potential additive effect on bleeding risk due to VEGFR inhibition. | Use with caution. Monitor for bruising, nosebleeds, and GI bleeding. |
| Pirfenidone | No clinically relevant pharmacokinetic interaction demonstrated. Both are antifibrotic agents. | Combination use is not routinely recommended outside clinical trials because of additive gastrointestinal toxicity. |
| Bosentan and other ERAs | Moderate P-gp and CYP3A4 inducer. May moderately reduce nintedanib exposure. | Monitor treatment efficacy. Often used concurrently in SSc-ILD patients with associated pulmonary arterial hypertension. |
| Corticosteroids | Possible additive risk of gastrointestinal perforation. No pharmacokinetic interaction expected. | Use with caution, particularly in long-term high-dose corticosteroid therapy. Consider gastroprotection. |
Nintedanib Zentiva should always be taken with food. Co-administration with food increases the bioavailability of nintedanib by approximately 20% compared with the fasted state and reduces inter-patient variability in plasma exposure. This is the recommended way to take the medication and was the method used in all pivotal clinical trials. Grapefruit juice should be avoided as theoretical CYP3A4 and P-gp inhibition could alter exposure.
What Is the Correct Dosage of Nintedanib Zentiva?
The recommended dose of nintedanib is 150 mg twice daily, taken approximately 12 hours apart with food. Because Nintedanib Zentiva is available as 100 mg soft capsules, doctors may prescribe this strength for dose reduction from 150 mg to 100 mg twice daily when needed to manage adverse reactions. Capsules must always be swallowed whole with water.
Dosing of Nintedanib Zentiva should be individualised based on tolerability rather than body weight or body surface area. Treatment should be initiated by a specialist physician experienced in the management of interstitial lung diseases. The capsules must be swallowed whole with water and must not be chewed, crushed, or opened, as the active substance may cause local irritation on contact with mucous membranes and direct contact may increase the risk of skin or eye reactions for caregivers. Taking the capsules with food is recommended to enhance absorption and reduce gastrointestinal side effects.
Adults
Standard Dosing for All Approved Indications
Recommended dose: 150 mg taken orally twice daily, approximately 12 hours apart, with food.
Dose reduction: If the full dose of 150 mg twice daily is not tolerated, the dose may be reduced to 100 mg twice daily using the Nintedanib Zentiva 100 mg capsule. If the reduced dose of 100 mg twice daily is also not tolerated, treatment should be discontinued rather than reduced further.
Treatment interruption: Transient treatment interruption may be used to manage adverse reactions such as significant liver enzyme elevations or severe diarrhea. Once adverse reactions have resolved, treatment can be reintroduced at 100 mg twice daily and, if tolerated, subsequently increased to 150 mg twice daily.
| Patient Group | Dose | Frequency | Special Considerations |
|---|---|---|---|
| Adults (IPF) | 150 mg (or 100 mg if reduced) | Twice daily with food | Monitor liver function and body weight. Reduce to 100 mg if GI side effects are intolerable. |
| Adults (SSc-ILD) | 150 mg (or 100 mg if reduced) | Twice daily with food | Same dose as IPF. May be used with background immunosuppressive therapy (e.g., mycophenolate mofetil). |
| Adults (progressive fibrosing ILD) | 150 mg (or 100 mg if reduced) | Twice daily with food | Indicated for patients showing progression despite standard management of the underlying ILD. |
| Mild hepatic impairment (Child-Pugh A) | 100 mg | Twice daily with food | Reduced starting dose recommended. Exposure approximately doubled. Close monitoring of LFTs required. |
| Moderate hepatic impairment (Child-Pugh B) | Not recommended | — | Not studied. Use not recommended due to significantly increased exposure and hepatotoxicity risk. |
| Severe hepatic impairment (Child-Pugh C) | Contraindicated | — | Do not use. Exposure is expected to be significantly increased with a high risk of serious hepatotoxicity. |
| Renal impairment | No dose adjustment needed | Standard dosing | Less than 1% of the dose is excreted renally. No clinically relevant change in exposure expected. |
Children and Adolescents
The safety and efficacy of Nintedanib Zentiva in children and adolescents under 18 years of age have not been established. There are currently no reliable data to support dosing in this population, and the use of nintedanib in paediatric patients is not recommended outside of clinical trials. Rare paediatric forms of progressive fibrosing ILD are actively being investigated in clinical research programmes; eligible patients should be discussed at a specialist ILD centre.
Elderly Patients
No dose adjustment is required based on age alone. Clinical trials included a substantial proportion of patients aged 65 years and older, and the safety and efficacy profile in older patients was consistent with the overall study population. However, elderly patients may be more susceptible to gastrointestinal adverse effects, dehydration secondary to diarrhea, and hepatotoxicity. Closer monitoring, earlier supportive care, and a lower threshold for dose reduction from 150 mg to 100 mg twice daily may be appropriate in patients over 75 years of age or in those with significant frailty or multimorbidity.
Missed Dose
If you forget to take a dose of Nintedanib Zentiva, skip the missed dose entirely and take the next scheduled dose at the usual time. Do not take a double dose to make up for the missed one, and do not take more than the total daily dose prescribed by your doctor within any 24-hour period. Consistency is more important than making up for single missed doses: try to take the medicine at approximately the same times each day, ideally with your morning and evening meals.
Overdose
There is limited clinical experience with overdose of nintedanib. The highest dose evaluated in short-term clinical trials was 450 mg once daily, which was associated with increased gastrointestinal adverse events, particularly diarrhea and nausea. In case of overdose, treatment should be symptomatic and supportive — there is no specific antidote for nintedanib. Given that nintedanib is approximately 97.8% protein-bound, haemodialysis is unlikely to meaningfully remove the drug. Seek immediate medical attention if you suspect an overdose.
Contact your local poison control centre or emergency department immediately if you suspect an overdose. Take the medication packaging with you so that the treating team can confirm the product and strength. Symptoms of overdose may include severe diarrhea, nausea, vomiting, abdominal pain, dehydration, and elevated liver enzymes.
What Are the Side Effects of Nintedanib Zentiva?
The most common side effects of Nintedanib Zentiva are gastrointestinal — particularly diarrhea (affecting more than 60% of patients), nausea, vomiting, abdominal pain, and decreased appetite. Elevated liver enzymes are also common and require regular monitoring. Most side effects can be managed with dose adjustment, supportive therapy, and, where needed, temporary treatment interruption.
Like all medicines, Nintedanib Zentiva can cause side effects, although not everybody experiences them. The safety profile of nintedanib has been extensively characterised in a clinical trial programme involving more than 3,000 patients across IPF, SSc-ILD, and progressive fibrosing ILD studies, as well as in large post-marketing registries such as INPULSIS-ON. The side effects below are classified by frequency according to the MedDRA convention used in European product information. Frequencies reflect pooled clinical trial data and may vary by indication.
Very Common (affects more than 1 in 10 patients)
- Diarrhea — the most frequent side effect (approximately 62% in IPF trials and up to 76% in SSc-ILD trials). Usually mild to moderate and manageable with loperamide, hydration, and dose adjustment.
- Nausea — reported in approximately 24% of patients. Taking capsules with food helps reduce nausea.
- Elevated liver enzymes (ALT, AST) — reported in approximately 14% of patients. Usually reversible with dose reduction or temporary interruption.
- Abdominal pain — including upper abdominal pain, reported in approximately 15% of patients.
- Vomiting — reported in approximately 12% of patients. Anti-emetic therapy may be helpful in persistent cases.
Common (affects 1 to 10 in every 100 patients)
- Decreased appetite — may contribute to weight loss over time.
- Weight loss — body weight should be monitored regularly during treatment.
- Headache — usually mild and transient.
- Elevated bilirubin — may indicate hepatic involvement and warrants prompt evaluation.
- Elevated gamma-glutamyltransferase (GGT) and alkaline phosphatase.
- Hypertension — blood pressure should be monitored during treatment.
- Bleeding events — including epistaxis (nosebleeds), bruising, haematuria, and menorrhagia.
- Dehydration — secondary to diarrhea and reduced oral intake.
Uncommon (affects 1 to 10 in every 1,000 patients)
- Pancreatitis — inflammation of the pancreas. Report severe abdominal pain radiating to the back.
- Thrombocytopenia — low platelet count, may increase bleeding risk.
- Drug-induced liver injury — serious liver damage requiring treatment discontinuation.
- Gastrointestinal perforation — a serious event requiring immediate medical attention.
- Rash — skin reactions including pruritus (itching) and dry skin.
- Proteinuria — protein in the urine, may require renal assessment.
Rare (affects fewer than 1 in 1,000 patients)
- Myocardial infarction (heart attack) — a higher incidence was observed in some studies. Patients with cardiovascular risk factors should be monitored.
- Posterior reversible encephalopathy syndrome (PRES) — reported post-marketing. Symptoms include headache, seizures, visual disturbances, and altered consciousness.
- Severe anaphylactic or anaphylactoid reactions — rare hypersensitivity reactions. Seek emergency medical care.
- Hepatic failure — fatal cases have been reported in post-marketing surveillance.
- Nephrotic syndrome — significant proteinuria with peripheral oedema and hypoalbuminaemia.
Contact your healthcare provider immediately if you experience: persistent or severe diarrhea lasting more than 24 hours; signs of liver problems (unexplained fatigue, dark urine, jaundice); unusual bleeding or bruising; severe abdominal pain; chest pain or symptoms of a heart attack; severe headache with visual changes; significant facial or peripheral swelling; or any other symptoms that concern you. Most side effects can be managed effectively with early intervention and dose adjustment, so prompt reporting is essential.
Reporting of suspected adverse reactions is an important part of ongoing medication safety. If you experience any side effect, you are encouraged to report it to your doctor, pharmacist, or national pharmacovigilance system. This helps regulators continue to monitor the safety profile of nintedanib in real-world use.
How Should You Store Nintedanib Zentiva?
Store Nintedanib Zentiva below 25°C in the original packaging to protect from moisture. Keep out of the reach and sight of children. Do not use after the expiry date printed on the packaging, and return any unused medicine to your pharmacy for safe disposal.
Proper storage of Nintedanib Zentiva is important to maintain the quality, stability, and efficacy of the medication. The soft gelatin capsules are moisture-sensitive and should remain in the original blister packaging until immediately before use. The following storage conditions apply:
- Temperature: Store below 25°C (77°F). Do not refrigerate or freeze, as freezing may compromise the integrity of the soft capsule shell.
- Moisture protection: Keep the capsules in the original blister packaging until ready to take. The blister provides protection from humidity, which can otherwise soften the soft capsule.
- Light protection: Store in the outer carton to protect from light.
- Shelf life: Do not use this medicine after the expiry date stated on the carton and blister after "EXP." The expiry date refers to the last day of that month.
- Children: Keep out of the reach and sight of children at all times. Store in a secure, elevated location.
- Travel: Carry Nintedanib Zentiva in your hand luggage when flying to avoid temperature extremes in aircraft holds. For extended travel, keep the medicine in the original packaging and away from direct sunlight.
- Disposal: Do not dispose of medications via wastewater or household waste. Return unused medicines to your pharmacy for safe disposal in accordance with local regulations — this helps protect the environment.
If you notice that the capsules have changed in appearance (discoloration, leakage, softening, or damage to the blister seal), do not take them. Contact your pharmacist for replacement. Soft capsules are sensitive to heat and should not be left in direct sunlight, in a hot car, or close to heaters or electrical appliances that generate warmth.
What Does Nintedanib Zentiva Contain?
Each Nintedanib Zentiva 100 mg soft capsule contains 100 mg of nintedanib (as the esylate salt) as the active substance, together with excipients including medium-chain triglycerides, soya lecithin, and a gelatin capsule shell.
Understanding the full composition of your medication is important, particularly if you have known allergies or dietary restrictions. Although the precise excipient list can vary slightly between manufacturers and countries, the composition of Nintedanib Zentiva 100 mg soft capsules is generally as follows, in line with the reference medicinal product:
Active substance: Each soft capsule contains 120.4 mg of nintedanib esylate, equivalent to 100 mg of nintedanib (free base).
Capsule contents (excipients):
- Medium-chain triglycerides — lipid-based vehicle used to solubilise the active substance.
- Hard fat — provides structural consistency to the capsule fill.
- Soya lecithin (E322) — emulsifier. Contains soya; contraindicated in patients with soya or peanut allergy.
Capsule shell:
- Gelatin — capsule shell material (of animal origin; of note for patients with religious or dietary restrictions).
- Glycerol (85%) — plasticiser for the gelatin shell.
- Titanium dioxide (E171) — opacifier.
- Iron oxide red (E172) — colorant.
- Iron oxide yellow (E172) — colorant.
Printing ink: Shellac, iron oxide black (E172), and propylene glycol are typically used for imprinting the capsule with identification markings. Please refer to the patient information leaflet supplied with your pack for the exact list of excipients.
Nintedanib Zentiva soft capsules contain soya lecithin. Patients with a known allergy to peanut or soya must not take this medicine. The gelatin capsule shell is of animal origin. If you have any other allergies, dietary restrictions, or religious considerations, discuss these with your pharmacist or doctor before starting treatment so that an appropriate formulation decision can be made.
Manufacturer and Marketing Authorisation
Nintedanib Zentiva is manufactured and marketed by Zentiva as a generic version of the originator medicine Ofev (nintedanib), which was developed and is marketed by Boehringer Ingelheim. Generic medicinal products are approved by national and European regulators (such as the EMA) only after demonstrating pharmaceutical and bioequivalence to the reference product, which means that they are expected to deliver the same therapeutic effect and safety profile. The availability of high-quality generic options such as Nintedanib Zentiva helps improve patient access to antifibrotic therapy and reduces the cost burden on healthcare systems.
Frequently Asked Questions About Nintedanib Zentiva
References
- Richeldi L, du Bois RM, Raghu G, et al. Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis. N Engl J Med. 2014;370(22):2071-2082. doi:10.1056/NEJMoa1402584
- Richeldi L, Costabel U, Selman M, et al. Efficacy of a Tyrosine Kinase Inhibitor in Idiopathic Pulmonary Fibrosis (TOMORROW trial). N Engl J Med. 2011;365(12):1079-1087. doi:10.1056/NEJMoa1103690
- Distler O, Highland KB, Gahlemann M, et al. Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease (SENSCIS trial). N Engl J Med. 2019;380(26):2518-2528. doi:10.1056/NEJMoa1903076
- Flaherty KR, Wells AU, Cottin V, et al. Nintedanib in Progressive Fibrosing Interstitial Lung Diseases (INBUILD trial). N Engl J Med. 2019;381(18):1718-1727. doi:10.1056/NEJMoa1908681
- 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. Am J Respir Crit Care Med. 2022;205(9):e18-e47. doi:10.1164/rccm.202202-0399ST
- European Medicines Agency. Summary of Product Characteristics — Ofev (nintedanib). EMA/CHMP. Revised 2024.
- U.S. Food and Drug Administration. Ofev (nintedanib) Prescribing Information. Revised 2024.
- British National Formulary. Nintedanib. BNF. Accessed January 2026.
- Wollin L, Wex E, Pautsch A, et al. Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis. Eur Respir J. 2015;45(5):1434-1445. doi:10.1183/09031936.00174914
- Crestani B, Huggins JT, Kaye M, et al. Long-term safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis: results from the open-label extension study, INPULSIS-ON. Lancet Respir Med. 2019;7(1):60-68. doi:10.1016/S2213-2600(18)30339-4
- World Health Organization. Model List of Essential Medicines. 23rd List, 2023.
About Our Medical Editorial Team
All content on iMedic is written and reviewed by qualified medical professionals. The editorial team for this article includes specialists in pulmonology and clinical pharmacology with extensive experience in the diagnosis and management of interstitial lung diseases and antifibrotic therapies.
iMedic Medical Editorial Team — Specialists in pulmonary medicine and pharmaceutical sciences with academic and clinical backgrounds in respiratory diseases and pharmacotherapy.
iMedic Medical Review Board — Independent panel including board-certified pulmonologists and clinical pharmacologists who verify all content against current international guidelines (ATS, ERS, EMA, FDA).
Evidence standard: All medical claims in this article are based on Level 1A evidence (systematic reviews and randomised controlled trials), including the INPULSIS, SENSCIS, and INBUILD clinical trial programmes, and on current international treatment guidelines. No commercial funding was involved in the creation of this content, and no pharmaceutical company sponsorship has influenced its preparation.