Nintedanib Lotus
Tyrosine kinase inhibitor for idiopathic pulmonary fibrosis and progressive fibrosing interstitial lung diseases
Quick Facts About Nintedanib Lotus
Key Takeaways About Nintedanib Lotus
- Slows disease progression: Nintedanib Lotus reduces the rate of lung function decline (FVC) by approximately 50% in patients with idiopathic pulmonary fibrosis, as demonstrated in the INPULSIS trials.
- Triple kinase inhibitor: It targets three key receptor families (VEGFR, FGFR, PDGFR) involved in the pathogenesis of pulmonary fibrosis, providing a multi-pathway antifibrotic effect.
- Diarrhea is the most common side effect: Occurring in over 60% of patients, diarrhea can usually be managed with dose adjustments and supportive care. Report persistent diarrhea to your doctor.
- Liver monitoring is essential: Liver function tests (ALT, AST, bilirubin) must be checked before starting treatment and monitored regularly, as nintedanib can cause drug-induced liver injury.
- Not suitable during pregnancy: Nintedanib Lotus has embryo-fetal toxicity. Women of childbearing potential must use effective contraception during treatment and for at least 3 months after the last dose.
What Is Nintedanib Lotus and What Is It Used For?
Nintedanib Lotus is a tyrosine kinase inhibitor that slows the progression of pulmonary fibrosis by blocking the signaling pathways that drive 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 Lotus contains the active substance nintedanib (as the esylate salt), a small molecule that belongs to the class of tyrosine kinase inhibitors. It was developed as an antifibrotic agent specifically targeting the molecular pathways responsible for the progressive scarring (fibrosis) that occurs in several serious lung conditions. The drug is available as soft capsules for oral administration in a strength of 100 mg.
Pulmonary fibrosis is a group of lung diseases characterized by progressive scarring of the lung tissue, which leads to a gradual and irreversible decline in lung function. In idiopathic pulmonary fibrosis (IPF), the most common and severe form, the cause of the scarring is unknown. The disease typically affects adults over the age of 50 and carries a median survival of only 3 to 5 years from diagnosis without treatment. The hallmark symptom is progressive breathlessness, initially on exertion and eventually at rest, accompanied by a persistent dry cough.
Nintedanib works by competitively binding to the adenosine triphosphate (ATP) binding pocket of three families of receptor tyrosine kinases 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 these receptors, nintedanib reduces the proliferation, migration, and transformation of fibroblasts into myofibroblasts, which are the key effector cells responsible for excessive collagen deposition and extracellular matrix remodeling in fibrotic lungs.
The clinical efficacy of nintedanib in IPF was established in three pivotal randomized controlled trials. The TOMORROW trial (Phase II) first demonstrated a clinically meaningful reduction in the annual rate of forced vital capacity (FVC) decline at the 150 mg twice-daily dose. This finding was subsequently confirmed in the two replicate INPULSIS trials (Phase III), published 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, establishing it as one of only two approved antifibrotic therapies for IPF worldwide.
Approved Indications
Nintedanib Lotus is approved for the following conditions:
- Idiopathic Pulmonary Fibrosis (IPF): The primary indication. Nintedanib slows the progression of IPF by reducing the rate of lung function decline. It is recommended as a conditional treatment option in the 2022 ATS/ERS/JRS/ALAT Clinical Practice Guideline for IPF.
- Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD): Based on the SENSCIS trial, nintedanib was shown to reduce the annual rate of FVC decline in patients with SSc-ILD, a serious complication of systemic sclerosis (scleroderma).
- Chronic Fibrosing Interstitial Lung Diseases with a Progressive Phenotype: Based on the INBUILD trial, nintedanib is also indicated for patients with other forms of chronic fibrosing ILD who show signs of disease progression despite standard management.
Nintedanib Lotus 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 physician experienced in the diagnosis and management of interstitial lung diseases.
What Should You Know Before Taking Nintedanib Lotus?
Before starting Nintedanib Lotus, 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. Certain drug interactions and pre-existing conditions require careful evaluation.
Contraindications
Nintedanib Lotus 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.
- Pregnancy: Nintedanib is contraindicated during pregnancy due to 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 last dose.
- Severe hepatic impairment: Nintedanib is contraindicated in patients with severe hepatic impairment (Child-Pugh C), as the drug is extensively metabolized by the liver and exposure may be significantly increased.
Warnings and Precautions
Your healthcare provider should be aware of and monitor for the following conditions and risks during treatment with Nintedanib Lotus:
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. If ALT or AST rises to more than 3 times the upper limit of normal (ULN), dose reduction 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.
Diarrhea: Diarrhea is the most frequently reported adverse reaction and can be severe. Patients should be advised to hydrate adequately and report persistent diarrhea to their doctor. Anti-diarrheal therapy (e.g., loperamide) should be started at the first signs of diarrhea. Dose reduction from 150 mg to 100 mg twice daily may be necessary. If severe diarrhea persists despite optimal supportive care, treatment discontinuation should be considered.
Nausea and vomiting: These gastrointestinal adverse effects are common and may contribute to decreased appetite and weight loss. Anti-emetic therapy and supportive care should be provided as needed. Dose reduction may be required in severe cases.
Bleeding risk: Nintedanib inhibits VEGFR, which plays a role in vascular homeostasis. Treatment may increase the risk of bleeding events. 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 patients with a known risk of bleeding if the anticipated benefit outweighs the potential risk.
Arterial thromboembolic events: An increased risk of myocardial infarction has been observed in some clinical studies. Patients with cardiovascular risk factors, including known coronary artery disease, should be monitored carefully. Treatment should be interrupted in patients who develop signs of acute myocardial ischemia.
Gastrointestinal perforation: Gastrointestinal perforation has been reported with nintedanib. Particular caution should be exercised in patients with previous abdominal surgery, recent history of gastrointestinal perforation, or concurrent use of corticosteroids or NSAIDs. Treatment should be permanently discontinued in patients who develop gastrointestinal perforation.
Liver function tests (ALT, AST, and bilirubin) must be performed prior to initiation of treatment and monitored at regular intervals. 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 skin or eyes), or right upper abdominal pain.
Pregnancy and Breastfeeding
Pregnancy: Nintedanib Lotus 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 use highly effective contraception during treatment. If a patient becomes pregnant while taking nintedanib, treatment must be stopped immediately and the patient informed of the potential hazard to the fetus.
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 with respect to fertility at the exposures studied, but the potential for impaired fertility in humans cannot be excluded based on the mechanism of action (VEGFR inhibition).
How Does Nintedanib Lotus Interact with Other Drugs?
Nintedanib is a substrate of P-glycoprotein (P-gp) and CYP3A4 to a minor extent. Co-administration with potent P-gp inhibitors may increase nintedanib exposure, while potent P-gp inducers may decrease it. Anticoagulants may increase the risk of bleeding when used concurrently.
Understanding drug interactions is essential for the safe use of Nintedanib Lotus. Nintedanib is primarily metabolized by hydrolytic ester cleavage, resulting in the free acid moiety BIBF 1202. Glucuronidation by UGT enzymes further produces the glucuronide BIBF 1202 glucuronide. CYP-dependent oxidation plays only a minor role in the biotransformation of nintedanib. Nintedanib, BIBF 1202, and BIBF 1202 glucuronide are substrates of P-glycoprotein (P-gp), which is the most clinically relevant transporter for drug interactions.
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 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 GI effects. |
| Rifampicin | Potent P-gp and CYP3A4 inducer. Decreased nintedanib AUC by ~50% and Cmax by ~60% | Avoid co-administration. Significantly reduces nintedanib efficacy. Select alternative agents. |
| Carbamazepine | Potent P-gp and CYP3A4 inducer. Expected to significantly decrease nintedanib exposure | Avoid co-administration. Consider alternative anti-epileptic with no P-gp induction. |
| Phenytoin | Potent CYP3A4 inducer and P-gp inducer. Expected to reduce nintedanib plasma levels | Avoid co-administration. Select alternative anti-epileptic medication. |
| St. John's Wort | Potent P-gp and CYP3A4 inducer. Expected to significantly reduce nintedanib exposure | Avoid concomitant use. Herbal supplement not recommended with nintedanib. |
Minor Interactions
| Interacting Drug | Effect | Clinical Recommendation |
|---|---|---|
| Warfarin / Anticoagulants | Nintedanib inhibits VEGFR, potentially increasing bleeding risk. Additive anticoagulant effect. | Monitor INR and signs of bleeding closely. Adjust anticoagulant dose as needed. |
| Antiplatelet agents (aspirin, clopidogrel) | Potential additive effect on bleeding risk due to VEGFR inhibition. | Use with caution. Monitor for signs of bleeding. |
| Pirfenidone | No clinically relevant pharmacokinetic interaction demonstrated. Both are antifibrotic agents. | Combination use not routinely recommended but under investigation in clinical studies. |
| Bosentan | Moderate P-gp and CYP3A4 inducer. May moderately reduce nintedanib exposure. | Monitor treatment efficacy. May be used concurrently in SSc-ILD patients on bosentan for PAH. |
Nintedanib Lotus should 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. This is the recommended way to take the medication and was the method used in all clinical trials.
What Is the Correct Dosage of Nintedanib Lotus?
The recommended dose of Nintedanib Lotus is 150 mg twice daily, taken approximately 12 hours apart with food. The 100 mg capsule strength allows for dose reduction when needed to manage adverse reactions. Capsules should be swallowed whole with water.
Dosing of Nintedanib Lotus should be individualized based on tolerability. Treatment should be initiated by a physician experienced in the management of interstitial lung diseases. The capsules must be swallowed whole with water and must not be chewed or crushed, as the active substance may cause irritation upon local contact with mucous membranes. 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 (one capsule of 150 mg or equivalent) 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. If the reduced dose of 100 mg twice daily is also not tolerated, treatment should be discontinued.
Note: Since Nintedanib Lotus is available as 100 mg soft capsules, doctors may prescribe two capsules per dose (200 mg equivalent) where the 150 mg capsule formulation is not available, or a single 100 mg capsule for dose reduction. Always follow your prescriber's specific instructions.
| Patient Group | Dose | Frequency | Special Considerations |
|---|---|---|---|
| Adults (IPF) | 150 mg (or 100 mg if reduced) | Twice daily with food | Monitor liver function. 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. Can be used with background immunosuppressive therapy (e.g., mycophenolate). |
| Adults (progressive fibrosing ILD) | 150 mg (or 100 mg if reduced) | Twice daily with food | Indicated for patients showing progression despite standard management of underlying ILD. |
| Mild hepatic impairment (Child-Pugh A) | 100 mg | Twice daily with food | Reduced starting dose recommended. Increased exposure (~2-fold) expected. Close monitoring required. |
| Moderate hepatic impairment (Child-Pugh B) | Not recommended | — | Not studied. Use not recommended due to potential for significantly increased exposure. |
| 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 Lotus in children and adolescents under 18 years of age have not been established. There are no data available. The use of nintedanib in pediatric populations is not recommended outside of clinical trials.
Elderly Patients
No dose adjustment is required based on age alone. Clinical trials included a substantial proportion of patients aged 65 years and older. In the INPULSIS trials, 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 and hepatotoxicity. Closer monitoring and a lower threshold for dose reduction may be appropriate in patients over 75 years of age.
Missed Dose
If you forget to take a dose of Nintedanib Lotus, skip the missed dose and take the next dose at the regularly scheduled time. Do not take a double dose to make up for a missed dose. There should be approximately 12 hours between two doses, but if the next scheduled dose is only a few hours away, simply continue with your regular dosing schedule.
Overdose
There is limited clinical experience with overdose of nintedanib. The highest dose studied in clinical trials was 450 mg once daily for a short period, which was associated with increased gastrointestinal adverse events. 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, hemodialysis is unlikely to be effective. Seek immediate medical attention in the event of an overdose.
Contact your local poison control center or emergency department immediately if you suspect an overdose. Bring the medication packaging with you. Symptoms of overdose may include severe diarrhea, nausea, vomiting, and abdominal pain.
What Are the Side Effects of Nintedanib Lotus?
The most common side effects of Nintedanib Lotus are gastrointestinal, particularly diarrhea (affecting over 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 and supportive care.
Like all medicines, Nintedanib Lotus can cause side effects, although not everybody gets them. The safety profile of nintedanib has been extensively characterized in large clinical trials involving over 3,000 patients. The following side effects are categorized by frequency according to international medical convention (MedDRA classification).
Very Common (affects more than 1 in 10 patients)
- Diarrhea — the most frequent side effect (~62% in IPF trials, ~76% in SSc-ILD trials). Usually mild to moderate and manageable with loperamide and hydration
- Nausea — reported in ~24% of patients. Taking capsules with food helps reduce nausea
- Elevated liver enzymes (ALT, AST) — reported in ~14% of patients. Usually reversible with dose reduction or interruption
- Abdominal pain — including upper abdominal pain, reported in ~15% of patients
- Vomiting — reported in ~12% of patients. Anti-emetic therapy may be helpful
Common (affects 1 to 10 in every 100 patients)
- Decreased appetite — may contribute to weight loss over time
- Weight loss — monitor body weight regularly during treatment
- Headache — usually mild and transient
- Elevated bilirubin — may indicate hepatic involvement
- Elevated gamma-glutamyltransferase (GGT)
- Hypertension — blood pressure should be monitored during treatment
- Bleeding events — including epistaxis (nosebleeds), bruising, and hematuria
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)
Rare (affects fewer than 1 in 1,000 patients)
- Myocardial infarction (heart attack) — higher incidence 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/anaphylactoid reactions — rare hypersensitivity reactions. Seek emergency medical care
- Hepatic failure — fatal cases have been reported post-marketing
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, yellowing of skin or eyes); unusual bleeding or bruising; severe abdominal pain; chest pain or symptoms of heart attack; severe headache with visual changes; or any other symptoms that concern you. Most side effects can be managed with early intervention and dose adjustment.
How Should You Store Nintedanib Lotus?
Store Nintedanib Lotus 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.
Proper storage of Nintedanib Lotus is important to maintain the quality and efficacy of the medication. The soft capsules should be stored in the original blister packaging until immediately before use to protect from moisture and light. The following storage conditions apply:
- Temperature: Store below 25°C (77°F). Do not refrigerate or freeze.
- Moisture protection: Keep the capsules in the original blister packaging until ready to take. The blister pack provides protection from moisture, which can affect the soft capsule integrity.
- 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.
- 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.
If you notice that the capsules have changed in appearance (discoloration, damage to the blister, or leakage), do not take them. Contact your pharmacist for replacement. Soft capsules are sensitive to heat and should not be left in direct sunlight or in a car during warm weather.
What Does Nintedanib Lotus Contain?
Each Nintedanib Lotus 100 mg soft capsule contains 100 mg of nintedanib (as the esylate salt) as the active substance, along with excipients including medium-chain triglycerides, soya lecithin, and gelatin capsule shell components.
Understanding the composition of your medication is important, particularly if you have known allergies or dietary restrictions. The complete composition of Nintedanib Lotus 100 mg soft capsules is as follows:
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 to solubilize 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)
- Glycerol (85%) — plasticizer 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), propylene glycol — used for imprinting the capsule with identification markings.
Nintedanib Lotus 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 or dietary restrictions, discuss these with your pharmacist or doctor before starting treatment.
Frequently Asked Questions About Nintedanib Lotus
References
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About Our Medical Editorial Team
All content on iMedic is written and reviewed by qualified medical professionals. Our editorial team for this article includes specialists in pulmonology and clinical pharmacology with extensive experience in the 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 randomized controlled trials), including the INPULSIS, SENSCIS, and INBUILD clinical trial programs, and current international treatment guidelines. No commercial funding was involved in the creation of this content.