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Nintedanib

Medically reviewed by Drugs.com. Last updated on May 5, 2020.

Pronunciation

(nin TED a nib)

Index Terms

  • BIBF1120
  • Nintedanib Esylate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Ofev: 100 mg, 150 mg

Brand Names: U.S.

  • Ofev

Pharmacologic Category

  • Tyrosine Kinase Inhibitor

Pharmacology

Inhibits multiple receptor tyrosine kinases (RTKs) and nonreceptor tyrosine kinases (nRTKs), including platelet-derived growth factor (PDGFR alpha and PDGFR beta); fibroblast growth factor receptor (FGFR1, FGFR2, FGFR3); vascular endothelial growth factor (VEGFR1, VEGFR2, and VEGFR3); colony-stimulating factor 1 receptor (CSF1R); and Fms-like tyrosine kinase-3 (FLT3). Nintedanib binds competitively to the adenosine triphosphate (ATP) binding pocket of these receptors and blocks the intracellular signaling which is crucial for the proliferation, migration, and transformation of fibroblasts.

Absorption

Food increases exposure ~20% and delays absorption

Distribution

Vss: 1050 L

Metabolism

Hydrolytic cleavage by esterases to free acid moiety BIBF 1202, which is then glucuronidated by UGT 1A1, UGT 1A7, UGT 1A8, and UGT 1A10 to BIBF 1202 glucuronide; CYP 3A4 (minor)

Excretion

Feces (~93%); urine (<1%)

Time to Peak

2 hours (4 hours with food)

Half-Life Elimination

9.5 hours

Protein Binding

~98%

Special Populations: Hepatic Function Impairment

In patients with mild hepatic impairment (Child-Pugh class A) and moderate impairment (Child-Pugh class B), the AUC is increased 2.2-fold and 7.6-fold, respectively, compared with patients with normal hepatic function.

Special Populations Note

Cigarette smoking: Exposure was 21% lower in smokers.

Use: Labeled Indications

Chronic fibrosing interstitial lung diseases with a progressive phenotype: Treatment of chronic fibrosing interstitial lung diseases (ILD) with a progressive phenotype.

Idiopathic pulmonary fibrosis: Treatment of idiopathic pulmonary fibrosis.

Systemic sclerosis-associated interstitial lung disease: Indicated to slow the rate of decline in pulmonary function in patients with systemic sclerosis-associated ILD.

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to nintedanib, peanut, or soya or any component of the formulation; pregnancy

Dosing: Adult

Chronic fibrosing interstitial lung diseases with a progressive phenotype: Oral: 150 mg every 12 hours (maximum: 300 mg/day).

Idiopathic pulmonary fibrosis: Oral: 150 mg every 12 hours (maximum: 300 mg/day).

Systemic sclerosis-associated interstitial lung disease: Oral: 150 mg every 12 hours (maximum: 300 mg/day).

Missed dose: If a dose is missed, the next dose should be taken at the next scheduled time. Do not make up a missed dose.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Gastrointestinal toxicity (eg, diarrhea, nausea, vomiting) or other adverse reactions/toxicity: Dose reduction or temporary interruption may be needed. Treatment may be resumed at 150 mg every 12 hours or 100 mg every 12 hours, which may subsequently be increased to 150 mg every 12 hours. If a patient does not tolerate 100 mg every 12 hours, discontinue treatment.

Administration

Oral: Administer with food. Swallow capsules whole with liquid; do not chew or crush (bitter taste).

Storage

Store at 25°C (77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Protect from high humidity and avoid excessive heat.

Drug Interactions

Anticoagulants: May enhance the adverse/toxic effect of Nintedanib. Specifically, the risk for bleeding may be increased. Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Nintedanib. Monitor therapy

Hormonal Contraceptives: Nintedanib may diminish the therapeutic effect of Hormonal Contraceptives. Management: Women of reproductive potential taking nintedanib and hormonal contraceptives concomitantly should add a barrier method of contraception during nintedanib treatment for at least 3 months after the last dose. Consider therapy modification

Inducers of CYP3A4 (Moderate) and P-glycoprotein: May decrease the serum concentration of Nintedanib. Avoid combination

Inducers of CYP3A4 (Strong) and P-glycoprotein: May decrease the serum concentration of Nintedanib. Avoid combination

Inhibitors of CYP3A4 (Moderate) and P-glycoprotein: May increase the serum concentration of Nintedanib. Monitor therapy

Inhibitors of CYP3A4 (Strong) and P-glycoprotein: May increase the serum concentration of Nintedanib. Monitor therapy

Letrozole: May increase the serum concentration of Nintedanib. Monitor therapy

Adverse Reactions

>10%:

Dermatologic: Dermal ulcer (18%)

Endocrine & metabolic: Weight loss (10% to 12%)

Gastrointestinal: Abdominal pain (15% to 18%), decreased appetite (9% to 11%), diarrhea (62% to 76%), nausea (24% to 32%), vomiting (12% to 25%)

Hepatic: Increased liver enzymes (13% to 14%)

Nervous system: Fatigue (10% to 11%)

Respiratory: Nasopharyngitis (13%)

1% to 10%:

Cardiovascular: Acute myocardial infarction (2%), arterial thrombosis (3%), hypertension (5%)

Endocrine & metabolic: Hypothyroidism (1%)

Genitourinary: Urinary tract infection (6%)

Hematologic & oncologic: Hemorrhage (10%; can be major hemorrhage)

Nervous system: Dizziness (6%), headache (8% to 9%)

Neuromuscular & skeletal: Back pain (6%)

Respiratory: Bronchitis (1%), pneumonia (4%), upper respiratory tract infection (7%)

Miscellaneous: Fever (6%)

<1%: Gastrointestinal: Gastrointestinal perforation

Postmarketing (any indication): Hepatotoxicity, pancreatitis, pruritus, skin rash, thrombocytopenia

Warnings/Precautions

Concerns related to adverse effects:

• Bleeding: May increase the risk of bleeding, especially epistaxis. Use in patients with known risk of bleeding only if the benefit outweighs the risk. Serious and nonserious bleeding events (some fatal) have been reported during postmarketing.

• Cardiovascular effects: Arterial thromboembolic events, including MI, have been reported. Use caution in patients at high cardiovascular risk, including in patients with known coronary artery disease. Consider treatment interruption in patients who develop signs or symptoms of acute myocardial ischemia.

• GI effects: Diarrhea, nausea, and vomiting may occur. Diarrhea occurred in over 50% of nintedanib-treated patients, and was generally of mild to moderate intensity and occurred within the first 3 months of treatment. Treat with appropriate supportive care (eg, adequate hydration, antidiarrheals, antiemetics); dose reduction and/or treatment interruption may be required. If GI effects do not resolve, discontinue treatment. In addition, nintedanib may increase the risk of GI perforation; cases of GI perforation (some fatal) have been reported during postmarketing. Use caution when treating patients who have had recent abdominal surgery, previous history of diverticular disease or who are receiving concomitant corticosteroids or NSAIDs; only use in patients at risk of perforation if the benefit outweighs the risk. It has been recommended to wait at least 4 weeks following abdominal surgery before initiating therapy (OFEV Canadian product monograph). Discontinue if perforation develops.

• Hepatic effects: Serious and nonserious cases of drug-induced liver injury (including severe liver injury with fatal outcome) have been reported. Hepatic effects usually occurred within the first 3 months of treatment. Elevations of ALT, AST, GGT, alkaline phosphatase, and bilirubin were usually reversible with dose modification or interruption. Risk may be increased in patients with a low body weight (<65 kg) and Asian and female patients. Obtain liver function tests prior to initiation of treatment, at regular intervals during the first 3 months of treatment, and periodically thereafter or as clinically indicated. Monitor for clinical signs/symptoms of liver injury (eg, fatigue, right upper abdominal discomfort, dark urine, jaundice); if reported, promptly obtain liver function tests. Dosage modifications or interruption may be necessary.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Hepatic impairment: Nintedanib is primarily eliminated through biliary/fecal excretion; use is not recommended in patients with moderate or severe hepatic impairment. Dose reduction is recommended in patients with mild impairment; if adverse reactions occur, consider treatment interruption or discontinuation.

• Smokers: Smoking may decrease exposure to nintedanib; patients should stop smoking prior to treatment and avoid smoking during therapy.

Monitoring Parameters

Obtain liver function tests prior to initiation of treatment, at regular intervals during the first 3 months of treatment, and periodically thereafter or as clinically indicated; obtain pregnancy test prior to treatment and periodically during treatment in women of reproductive potential. Monitor for GI events (eg, diarrhea, nausea, vomiting), arterial thromboembolic events, bleeding, and GI perforation.

Reproductive Considerations

A pregnancy test is required prior to initiating treatment and periodically during treatment in women of reproductive potential. Women of reproductive potential should use highly effective contraception during therapy and for ≥3 months after the last dose; the addition of a barrier method is recommended if a hormonal contraceptive is used.

Pregnancy Considerations

Based on the mechanism of action and adverse events observed in animal reproduction studies, nintedanib may be expected to cause fetal harm if used during pregnancy.

Patient Education

What is this drug used for?

• It is used to treat idiopathic pulmonary fibrosis (IPF) or certain other lung problems.

• It is used to slow the progress of lung disease in some people.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Lack of appetite

• Weight loss

• Fatigue

• Loss of strength and energy

• Diarrhea

• Nausea

• Vomiting

• Common cold symptoms

• Nose irritation

• Throat irritation

• Back pain

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding

• Blood clots like numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; chest pain; shortness of breath; fast heartbeat; or coughing up blood

• Urinary tract infection like blood in your urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain

• Heart attack like chest pain; pain in arms, back, neck, jaw, or abdomen; shortness of breath; cold sweats; severe dizziness; passing out; or severe nausea or vomiting

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes

• Severe abdominal pain

• Abdominal swelling

• Severe headache

• Severe dizziness

• Passing out

• Vision changes

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.