Nifibro (Nintedanib)

What Is Nifibro and What Is It Used For?

Nifibro is a prescription medicine containing the active substance nintedanib, classified as a tyrosine kinase inhibitor. It is primarily indicated for the treatment of idiopathic pulmonary fibrosis (IPF) in adult patients. IPF is a chronic, progressive disease characterized by the irreversible scarring (fibrosis) of lung tissue, which leads to a gradual decline in lung function, worsening breathlessness, and reduced quality of life. There is currently no cure for IPF, but Nifibro can significantly slow the rate at which the disease progresses.

The mechanism of action of nintedanib involves competitive inhibition of the adenosine triphosphate (ATP) binding pocket of three families of receptor tyrosine kinases: 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). These receptors play critical roles in the signalling pathways that promote fibroblast proliferation, migration, and transformation into myofibroblasts, which are the primary cells responsible for excessive collagen deposition and fibrotic tissue remodelling in the lungs.

In addition to IPF, nintedanib may also be prescribed for other forms of chronic progressive fibrosing interstitial lung diseases (ILDs) and for systemic sclerosis-associated interstitial lung disease (SSc-ILD). In these conditions, the fibrotic process in the lungs follows a similar pattern to IPF, and nintedanib has been shown to slow the decline in forced vital capacity (FVC) across these indications as well. The pivotal INBUILD trial demonstrated that nintedanib reduced the annual rate of FVC decline in patients with progressive fibrosing ILDs regardless of the underlying disease pattern.

The clinical efficacy of Nifibro was established in the landmark INPULSIS-1 and INPULSIS-2 phase III randomized, double-blind, placebo-controlled trials, which enrolled over 1,000 patients with IPF. These trials demonstrated that nintedanib 150 mg twice daily reduced the annual rate of decline in FVC by approximately 50% compared to placebo (approximately -115 mL/year vs -240 mL/year). This represents a clinically meaningful preservation of lung function over time, although it does not reverse existing fibrosis or completely halt disease progression.

Nifibro is intended for long-term use as part of the ongoing management of pulmonary fibrosis. Patients are advised to continue treatment as long as clinical benefit is observed and the medicine is tolerated. Treatment should be supervised by a physician experienced in the diagnosis and management of interstitial lung diseases.

What Should You Know Before Taking Nifibro?

Contraindications

Nifibro must not be used in the following situations:

• Hypersensitivity to nintedanib, peanut, soya, or any of the excipients in the capsule formulation
• Pregnancy – nintedanib has demonstrated reproductive toxicity in preclinical animal studies and is expected to cause harm to the developing fetus
• Severe hepatic impairment (Child-Pugh C) – nintedanib is extensively metabolized by the liver and exposure is significantly increased in patients with severe liver disease

Warnings and Precautions

Before starting Nifibro, your prescribing physician will perform a thorough assessment that includes liver function tests, a review of your cardiovascular risk factors, and an evaluation of any bleeding risk. Several important warnings apply during treatment:

Hepatotoxicity: Nintedanib can cause drug-induced liver injury. Elevations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin have been reported. Liver function tests should be performed before starting treatment, at regular monthly intervals for the first three months, and periodically thereafter. If liver enzyme elevations exceed 3 times the upper limit of normal (ULN), dose reduction or temporary treatment interruption is recommended. Permanent discontinuation is necessary if elevations exceed 5 times ULN or if signs and symptoms of severe liver damage (such as jaundice) develop.

Diarrhea: This is the most frequently reported adverse event and may be severe. Patients should be advised on adequate hydration and anti-diarrheal medications (such as loperamide) at the first signs of diarrhea. If diarrhea persists despite supportive measures, dose reduction from 150 mg twice daily to 100 mg twice daily should be considered. Treatment should be discontinued if severe diarrhea persists despite medical management.

Bleeding risk: Nintedanib is a VEGFR inhibitor and may theoretically increase the risk of bleeding. Patients with a known predisposition to bleeding, including those receiving full-dose anticoagulant therapy, should be monitored closely. Treatment should only be initiated after careful consideration of the risk-benefit ratio in patients who have recently undergone major surgery.

Cardiovascular risk: An increased rate of myocardial infarction and other arterial thromboembolic events has been observed in clinical trials. Caution is advised in patients with significant cardiovascular risk factors, including known coronary artery disease. Treatment should be interrupted in patients who develop signs or symptoms suggestive of an acute arterial thromboembolic event.

Gastrointestinal perforation: Cases of gastrointestinal perforation have been reported in patients receiving nintedanib. Use with caution in patients who have had previous abdominal surgery, those with a history of diverticular disease, or those receiving concurrent corticosteroids or non-steroidal anti-inflammatory drugs (NSAIDs). Discontinue Nifibro permanently if gastrointestinal perforation occurs.

Pregnancy and Breastfeeding

Pregnancy: Nifibro is contraindicated during pregnancy. Nintedanib has demonstrated embryo-fetal toxicity and teratogenicity in animal reproductive studies. Women of childbearing potential must use highly effective contraception during treatment and for at least 3 months after the last dose. A pregnancy test should be performed before initiating therapy. If a patient becomes pregnant while taking Nifibro, the treatment must be stopped immediately and the patient should be informed about the potential risks to the fetus.

Breastfeeding: It is not known whether nintedanib or its metabolites are excreted in human breast milk. A risk to breastfed infants cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue treatment with Nifibro, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Fertility: Based on non-clinical data, nintedanib may have the potential to impair male fertility. The clinical significance of this finding is not known.

How Does Nifibro Interact with Other Drugs?

Drug interactions with nintedanib are primarily mediated through P-glycoprotein (P-gp) transport and, to a lesser extent, CYP3A4 metabolism. Nintedanib is predominantly metabolized by hydrolytic esterases rather than cytochrome P450 enzymes, which limits the potential for clinically relevant CYP-mediated drug interactions. However, because nintedanib is a substrate of P-gp, co-administration with inhibitors or inducers of this transporter can significantly affect its plasma concentrations.

Patients should inform their healthcare provider about all prescription medications, over-the-counter drugs, herbal supplements, and dietary products they are currently taking. This is particularly important for medications that affect P-gp transport or that carry their own risk of hepatotoxicity, gastrointestinal complications, or bleeding.

Major Interactions

P-glycoprotein inhibitors represent the most clinically significant drug interaction category for nintedanib. Co-administration of Nifibro with potent P-gp inhibitors such as ketoconazole or erythromycin increases the systemic exposure (AUC) of nintedanib by approximately 60%, and peak plasma concentrations (Cmax) by approximately 80%. While no specific dose adjustment is mandated, patients should be closely monitored for adverse effects, particularly diarrhea and liver enzyme elevations, and dose reduction to 100 mg twice daily should be considered if the combination is not well tolerated.

P-glycoprotein inducers such as rifampicin, carbamazepine, phenytoin, and the herbal supplement St. John's Wort can reduce nintedanib plasma exposure by approximately 50%, which may compromise therapeutic efficacy. Co-administration with potent P-gp and CYP3A4 inducers should be avoided. If concurrent use is unavoidable, patients should be monitored for signs of reduced treatment effect.

Minor Interactions

Nintedanib has a low potential for CYP-mediated interactions because its primary metabolism occurs via esterase-catalyzed hydrolysis. It is not a significant inhibitor or inducer of CYP enzymes at therapeutic concentrations. However, since a minor fraction of nintedanib metabolism involves CYP3A4, there may be a small additional pharmacokinetic effect when strong CYP3A4 inhibitors or inducers are co-administered alongside P-gp modulating drugs.

There is no clinically significant interaction with oral contraceptives, proton pump inhibitors, or H2-receptor antagonists. The bioavailability of nintedanib is approximately 5% on an empty stomach and increases when taken with food; therefore, consistent administration with meals is recommended for predictable drug exposure.

What Is the Correct Dosage of Nifibro?

Nifibro (nintedanib) dosing should be individualized based on patient tolerance and clinical response. The medicine is available as 100 mg soft capsules, and dosing may involve combining capsules to achieve the target dose. All dose changes should be made under the supervision of a physician experienced in managing interstitial lung diseases.

Adults

The recommended dose for adult patients with idiopathic pulmonary fibrosis, systemic sclerosis-associated ILD, or other chronic progressive fibrosing interstitial lung diseases is 150 mg taken orally twice daily. The two daily doses should be taken approximately 12 hours apart (for example, at 8 AM and 8 PM) and always with food, as this increases bioavailability and reduces gastrointestinal side effects. Nifibro 100 mg capsules can be used to achieve the 150 mg dose in combination with 50 mg capsules where available, or by physician-directed dosing using available strengths.

Capsules must be swallowed whole with a glass of water. They should not be chewed, crushed, or opened, as the contents have a bitter taste and may cause local irritation of the oropharynx if released outside the capsule shell. Treatment should be continued indefinitely for as long as clinical benefit is observed and the medication is tolerated.

Children

Nifibro is not indicated for use in children and adolescents under 18 years of age. The safety and efficacy of nintedanib have not been established in the pediatric population. Idiopathic pulmonary fibrosis is predominantly a disease of older adults, and there is no clinical rationale for nintedanib use in children. No pediatric studies have been conducted.

Elderly

No dose adjustment is required based solely on age. In the INPULSIS clinical trials, approximately 60% of enrolled patients were aged 65 years or older, and efficacy and safety profiles were generally consistent across age groups. However, elderly patients may be at increased risk of adverse events, particularly diarrhea and hepatic reactions, due to reduced physiological reserve. Close monitoring is recommended in patients older than 75 years, and a lower starting dose of 100 mg twice daily may be considered on an individual basis if tolerability is a concern.

Missed Dose

If a dose of Nifibro is missed, the patient should skip the missed dose and take the next scheduled dose at the usual time. The maximum recommended daily dose is 300 mg (150 mg twice daily). Patients should not take a double dose to compensate for a missed one. If doses are frequently missed, patients should discuss alternative strategies with their physician to improve adherence, such as setting daily reminders.

Overdose

There is limited clinical experience with overdose of nintedanib. In clinical trials, single doses of up to 450 mg once daily and doses of 300 mg twice daily for up to 28 days were investigated. The adverse events observed at these higher doses were consistent with the known safety profile, with gastrointestinal symptoms (diarrhea, nausea, vomiting) and liver enzyme elevations being the primary concerns.

In the event of an overdose, treatment should be discontinued, and general supportive measures should be initiated as appropriate. There is no specific antidote for nintedanib. Due to the high protein binding of nintedanib (approximately 97.8%), hemodialysis is unlikely to be effective in removing the drug from the circulation. Patients should be monitored for gastrointestinal adverse effects and liver function should be checked.

What Are the Side Effects of Nifibro?

Like all medicines, Nifibro can cause side effects, although not everybody experiences them. The safety profile of nintedanib has been well characterized through multiple large-scale randomized controlled trials (INPULSIS-1, INPULSIS-2, INBUILD, SENSCIS) involving thousands of patients. The most commonly reported adverse events are gastrointestinal in nature, particularly diarrhea, which is consistent with the pharmacological activity of nintedanib as a tyrosine kinase inhibitor.

Patients should be aware that many side effects of Nifibro can be effectively managed without stopping treatment. Early intervention with supportive measures such as adequate hydration, anti-diarrheal medications, and anti-emetics is important. Your doctor may reduce the dose from 150 mg twice daily to 100 mg twice daily if side effects are troublesome, and treatment may be temporarily interrupted if necessary.

When to seek immediate medical attention: Contact your doctor or seek emergency care immediately if you experience severe or persistent diarrhea with signs of dehydration (dizziness, dark urine, confusion), sudden chest pain or shortness of breath, signs of liver damage (yellowing of skin or eyes, dark urine, persistent fatigue), severe abdominal pain that may indicate gastrointestinal perforation, or any signs of a severe allergic reaction.

The overall discontinuation rate due to adverse events in clinical trials was approximately 20-25% in the nintedanib group compared to 15% in the placebo group. Dose reductions were used in approximately 25-30% of patients receiving nintedanib, primarily due to diarrhea. With appropriate dose management and supportive care, the majority of patients are able to continue treatment long-term.

How Should You Store Nifibro?

Proper storage of Nifibro is important to ensure the medication remains effective and safe throughout its shelf life. Nintedanib soft capsules contain a liquid fill that is sensitive to environmental conditions, and improper storage can affect the integrity and bioavailability of the active substance.

• Temperature: Store at or below 25°C (77°F). Do not refrigerate or freeze. Brief exposure to temperatures up to 30°C is acceptable during transport but should be minimized.
• Moisture protection: Keep capsules in the original blister packaging until immediately before use. The blister provides protection from moisture that could degrade the soft capsule shell.
• Light protection: Store in the original carton to protect from light when not in use.
• Shelf life: Do not use Nifibro after the expiry date (EXP) printed on the blister and carton. The expiry date refers to the last day of that month.
• Disposal: Do not dispose of unused capsules in household waste or wastewater. Return unused or expired medication to a pharmacy for proper disposal in accordance with local environmental regulations.
• Child safety: Keep this medicine out of the sight and reach of children. Store in a secure location, as accidental ingestion by children could cause serious harm.

If you notice any change in the appearance of the capsules (discoloration, damage, leaking, or unusual odor), do not take them and consult your pharmacist. Soft capsules that appear swollen, stuck together, or damaged may have been compromised and should not be used.

What Does Nifibro Contain?

Understanding the composition of your medication is important, particularly if you have known allergies or intolerances to specific excipients. Nifibro soft capsules are formulated as a solution of nintedanib esilate within a soft gelatin capsule shell.

Active Ingredient

Each Nifibro 100 mg soft capsule contains 100 mg of nintedanib (as nintedanib esilate). Nintedanib esilate is the ethanesulfonate salt form of nintedanib, which improves the pharmaceutical properties of the active substance. The molecular formula of nintedanib is C₃₁H₃₃N₅O₄, with a molecular weight of 539.62 g/mol for the free base.

Inactive Ingredients (Excipients)

The excipients in Nifibro soft capsules include:

• Capsule fill: Medium-chain triglycerides, hard fat, soya lecithin (E322)
• Capsule shell: Gelatin, glycerol (85%), titanium dioxide (E171), iron oxide red (E172), iron oxide yellow (E172)
• Printing ink: Shellac, iron oxide black (E172), propylene glycol

The soft capsule formulation has been selected for nintedanib because it provides optimal drug dissolution and absorption characteristics. The capsules are oblong in shape, opaque, and colored (typically brownish-orange for the 100 mg strength), with dosage strength markings printed on the shell for identification. The gelatin used in the capsule shell is of bovine or porcine origin, which may be relevant for patients with specific dietary or religious requirements.