Dosing & Uses
Dosage Forms & Strengths
capsule
- 100mg
- 150mg
Idiopathic Pulmonary Fibrosis
Indicated for idiopathic pulmonary fibrosis
150 mg PO q12hr
Chronic Fibrosing Interstitial Lung Diseases with a Progressive Phenotype
Indicated for chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype
Unclassifiable ILDs, autoimmune ILDs, chronic hypersensitivity pneumonitis, sarcoidosis, myositis, Sjögren syndrome, coal workers pneumoconiosis, and idiopathic forms of interstitial pneumonias (eg, idiopathic nonspecific interstitial pneumonia) are among the diseases that may develop a progressive form of chronic fibrosing ILD
150 mg PO q12hr
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 (SSc-ILD)
150 mg PO q12hr
Dosage Modifications
Dosage modifications due to adverse reactions
- Adverse reactions may require dose reduction or temporary interruption until the specific adverse reaction resolves
- Resumed at 150 mg q12hr, or at 100 mg q12hr, which subsequently may be increased to the full dose (150 mg q12hr)
- If 100 mg q12hr is not tolerated, discontinue treatment
Elevated liver enzymes
- AST/ALT >3 to <5x ULN without signs of severe liver damage: Interrupt treatment or reduce to 100 mg BID; once LFTs return to normal, may reintroduce at 100 mg BID, which subsequently may be increased to 150 mg BID
- AST/ALT >5x ULN or >3x ULN with signs/symptoms of severe liver damage: Discontinue
Hepatic impairment
- Mild (Child Pugh A): 100 mg PO q12hr
- Moderate-to-severe (Child Pugh B or C): Not recommended (not studied)
Renal impairment
- Mild-to-moderate: No dosage adjustment required
- Severe (CrCl <30 mL/min) or ESRD: Not studied
Dosing Considerations
Laboratory testing before initiating
- Conduct liver function tests in all patients
- Obtain pregnancy test in females of reproductive potential
Mesothelioma (Orphan)
Orphan designation for treatment of mesothelioma
Sponsor
- Boehringer Ingelheim Pharmaceuticals, Inc; 900 Ridgebury Rd, Box 368; Ridgefield, CT 06877
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
Idiopathic pulmonary fibrosis
- Diarrhea (62%)
- Nausea (24%)
- Abdominal pain (15%)
- Elevated liver enzymes (14%)
- Vomiting (12%)
- Decreased appetite (11%)
SSc-ILD
- Diarrhea (76%)
- Nausea (32%)
- Vomiting (25%)
- Skin ulcer (18%)
- Abdominal pain (18%)
- Liver enzyme elevation (13%)
- Decreased weight (12%)
- Fatigue (11%)
1-10%
Idiopathic pulmonary fibrosis
- Decreased weight (10%)
- Bleeding events (10%)
- Headache (8%)
- Hypertension (5%)
- Arterial thromboembolic events (2.5%)
- Myocardial infarction (1.5%)
- Bronchitis (1.5%)
- Hypothyroidism (1.1%)
SSc-ILD
- Decreased appetite (9%)
- Headache (9%)
- Pyrexia (6%)
- Back pain (6%)
- Dizziness (6%)
- Hypertension (5%)
<1%
Idiopathic pulmonary fibrosis
- Pneumonia (0.7%)
- Lung neoplasm malignant (0.3%)
- Gastrointestinal perforation (0.3%)
Postmarketing Reports
Pancreatitis
Thrombocytopenia
Drug-induced liver injury
Rash
Pruritus
Alopecia
Warnings
Contraindications
None
Cautions
Severe liver injury with fatal outcome reported; majority of hepatic events occur within first 3 months of treatment; conduct liver function tests (ALT, AST, and bilirubin) before initiating, monthly for 3 months, and then q3months thereafter and as clinically indicated
Not recommended in patients with moderate or severe hepatic impairment (Child Pugh B or C); reduced dose for patients with mild hepatic impairment (Child Pugh A)
Nausea, and/or vomiting may occur; treat with adequate hydration and antidiarrheal/antiemetic medications; if persists, treatment interruption and dose reduction may be needed
Diarrhea may occur; treat at first signs with adequate hydration and antidiarrheal medication (eg, loperamide); consider treatment interruption if diarrhea continues; treatment may be resumed at full dosage (150 mg twice daily), or at reduced dosage (100 mg twice daily); may subsequently increase to full dosage; if severe diarrhea persists despite symptomatic treatment, discontinue treatment
Arterial thromboembolic events reported, including myocardial infarction; caution when treatment patients at higher cardiovascular risk
May increased risk of bleeding or gastrointestinal perforation (based on mechanism of action [VEGFR inhibition]); monitor for bleeding if on full anticoagulant therapy and adjust anticoagulation treatment as needed
Smoking associated with decreased systemic exposure; encourage patients to quit smoking
Can cause fetal harm; use adequate contraception during treatment and for at least 3 months after the last dose
In postmarketing period non-serious and serious bleeding events reported; use therapy in patients with known risk of bleeding only if anticipated benefit outweighs potential risk
In postmarketing period, cases of gastrointestinal perforations reported; use caution when treating patients who have had recent abdominal surgery, previous history of diverticular disease or receiving concomitant corticosteroids or NSAIDs; discontinue therapy in patients who develop gastrointestinal perforation; only use in patients with known risk of gastrointestinal perforation if the anticipated benefit outweighs the potential risk
Drug interaction overview
- Nintedanib is a substrate of CYP3A4 and P-gp transporter
- Coadministration with potent P-gp or CYP3A4 inhibitors may increase systemic exposure of nintedanib (monitor closely)
- Coadministration with P-gp or CYP3A4 inducers may decrease systemic exposure to nintedanib by 50%; avoid coadministration
- Nintedanib is a VEGFR inhibitor and may increase bleeding risk; monitor patients on full anticoagulation for bleeding and adjust anticoagulation treatment if needed
Pregnancy & Lactation
Pregnancy
Based on findings from animal studies and its mechanism of action, can cause fetal harm when administered to pregnant women
Verify pregnancy status of females of reproductive potential prior to treatment
Animal data
- In animal studies of pregnant rats and rabbits treated during organogenesis, nintedanib caused embryofetal deaths and structural abnormalities at less than (rats) and ~5 times (rabbits) the maximum recommended human dose
Contraception
- Advise females of reproductive potential to avoid becoming pregnant while receiving nintedanib
- Use effective contraception during treatment, and for at least 3 months after taking the last dose
Infertility
- Based on animal data, may reduce fertility in females of reproductive potential
Lactation
There is no information on the presence of nintedanib in human milk, the effects on the breast-fed infant or the effects on milk production
Nintedanib and/or its metabolites are present in the milk of lactating rats
Because of the potential for serious adverse effects in breastfed infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Tyrosine kinase inhibitor; targets growth factors, which have been shown to be potentially involved in pulmonary fibrosis (eg, vascular endothelial growth factor receptor [VEGFR], fibroblast growth factor receptor [FGFR], platelet-derived growth factor receptor [PDGF])
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, representing essential mechanisms of the IPF pathology
Absorption
Bioavailability: 4.7%; undergoes substantial first-pass metabolism
Peak plasma concentration: 2-4 hr
Food increases systemic exposure by ~20% and delays peak level to ~4 hr
Distribution
Protein bound: 97.8%
Vd: 1050 L
Metabolism
Hydrolytic cleavage by esterases resulting in the free acid moiety BIBF 1202 is the prevalent metabolic pathway (~25%); BIBF 1202 is subsequently glucuronidated by UGT enzymes, namely UGT 1A1, UGT 1A7, UGT 1A8, and UGT 1A10 to BIBF 1202 glucuronide
Only a minor extent of the biotransformation consists of CYP pathways (~5%), with CYP3A4 being the predominant enzyme involved
Elimination
Excretion: 93.4% feces/biliary; 0.65% urine
Administration
Oral Administration
Take with food
Swallow capsule whole with liquid; do not chew or crush (bitter taste); effect of crushing on the pharmacokinetics is unknown
Missed dose: Take next dose at next scheduled time; advise patient to not make up for a missed dose
Storage
Store at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF)
Protect from exposure to high humidity and avoid excessive heat
If repackaged, use USP tight container
Keep out of reach of children
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Formulary
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