Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Ofev: 100 mg, 150 mg
Pharmacology
Mechanism of Action
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.
Pharmacokinetics/Pharmacodynamics
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%
Use in Specific Populations
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
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 interstitial lung disease.
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
Dosage and Administration
Dosing: Adult
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
Combined Inducers of CYP3A4 and P-glycoprotein: May decrease the serum concentration of Nintedanib. Avoid combination
Combined Inhibitors of CYP3A4 and P-glycoprotein: May increase the serum concentration of Nintedanib. Monitor therapy
Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy
Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Avoid combination
Lumacaftor and Ivacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor and Ivacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy
Adverse Reactions
>10%:
Gastrointestinal: Diarrhea (62%), nausea (24%), abdominal pain (15%), vomiting (12%), decreased appetite (11%)
Hepatic: Increased liver enzymes (14%)
1% to 10%:
Cardiovascular: Hypertension (5%), arterial thrombosis (3%), myocardial infarction (2%)
Central nervous system: Headache (8%)
Endocrine & metabolic: Weight loss (10%), hypothyroidism (1%)
Hematologic and oncologic: Hemorrhage (10%)
Respiratory: Bronchitis (1%)
<1%, postmarketing, and/or case reports: Gastrointestinal perforation, hemorrhage, hepatotoxicity, major hemorrhage, pancreatitis, pruritus, skin rash, thrombocytopenia
Warnings/Precautions
Concerns related to adverse effects:
- Bleeding: May increase the risk of bleeding. 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.
Pregnancy
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.
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.
Patient Education
What is this drug used for?
- It is used to treat idiopathic pulmonary fibrosis.
- It is used to slow the progress of lung disease in some people.
Frequently reported side effects of this drug
- Lack of appetite
- Weight loss
- Fatigue
- Loss of strength and energy
- Diarrhea
- Nausea
- Vomiting
- Back pain
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- 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
- Severe cerebrovascular disease like change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or vision changes
- 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 a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of 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 brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
