Version May 2024
Idiopathic pulmonary fibrosis: Oral: 150 mg every 12 hours; maximum daily dose: 300 mg/day.
Progressive pulmonary fibrosis: Oral: 150 mg every 12 hours; maximum daily dose: 300 mg/day.
Systemic sclerosis–associated interstitial lung disease: Oral: 150 mg every 12 hours; maximum daily dose: 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.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥30 mL/minute: No initial dosage adjustment necessary.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
ESRD: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hepatic impairment at baseline:
Mild impairment (Child-Pugh class A): Oral: 100 mg every 12 hours. If a patient does not tolerate 100 mg every 12 hours, consider treatment interruption or discontinue treatment to manage adverse reactions.
Moderate to severe impairment (Child-Pugh class B or C): Oral: Use is not recommended (exposure is increased in moderate impairment; has not been studied in severe impairment).
Hepatotoxicity during treatment:
AST or ALT >3 times to <5 times ULN (without signs of liver damage): Interrupt treatment or reduce dosage to 100 mg every 12 hours. Once liver enzymes have returned to baseline values after treatment interruption, reintroduce therapy at 100 mg every 12 hours; may be subsequently increased to 150 mg every 12 hours.
AST or ALT >5 times ULN or >3 times ULN with signs or symptoms of liver damage: Discontinue therapy.
Gastrointestinal toxicity (eg, diarrhea, nausea, vomiting) or other adverse reactions/toxicity: Dose reduction to 100 mg every 12 hours 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.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>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 (3% to 4%), upper respiratory tract infection (7%)
Miscellaneous: Fever (6%)
<1%: Gastrointestinal: Gastrointestinal perforation
Postmarketing:
Dermatologic: Pruritus, skin rash
Gastrointestinal: Pancreatitis
Genitourinary: Proteinuria
Hematologic & oncologic: Thrombocytopenia
Hepatic: Hepatoxicity
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to nintedanib, peanut, or soya or any component of the formulation; pregnancy
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), Asian patients, female patients, and older patients. Obtain LFTs 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 LFTs. Dosage modifications or interruption may be necessary.
• Nephrotic range proteinuria: Proteinuria within the nephrotic range has been reported. Histological findings were consistent with glomerular microangiopathy with or without renal thrombi. Usually improved when treatment was discontinued; some cases of residual proteinuria did persist. Consider treatment interruption in patients with new or worsening proteinuria.
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Ofev: 100 mg, 150 mg
No
Capsules (Ofev Oral)
100 mg (per each): $259.93
150 mg (per each): $259.93
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Ofev: 100 mg [contains soybean lecithin]
Ofev: 150 mg
Oral: Administer with food. Swallow capsules whole with liquid; do not open, chew, or crush (bitter taste). If exposure to capsule contents occurs, wash hands immediately and thoroughly.
Idiopathic pulmonary fibrosis: Treatment of idiopathic pulmonary fibrosis.
Progressive pulmonary fibrosis : Treatment of chronic progressive fibrosing interstitial lung diseases.
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.
Nintedanib may be confused with enasidenib, erlotinib, imatinib, neratinib, nilotinib, niraparib, vandetanib.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.
Substrate of CYP3A4 (minor), OCT1, P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Anticoagulants: May enhance the adverse/toxic effect of Nintedanib. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Nintedanib. Risk C: Monitor therapy
Inducers of CYP3A4 (Moderate) and P-glycoprotein: May decrease the serum concentration of Nintedanib. Risk X: Avoid combination
Inducers of CYP3A4 (Strong) and P-glycoprotein: May decrease the serum concentration of Nintedanib. Risk X: Avoid combination
Inhibitors of CYP3A4 (Moderate) and P-glycoprotein: May increase the serum concentration of Nintedanib. Risk C: Monitor therapy
Inhibitors of CYP3A4 (Strong) and P-glycoprotein: May increase the serum concentration of Nintedanib. Risk C: Monitor therapy
Letrozole: May increase the serum concentration of Nintedanib. Risk C: Monitor therapy
Tobacco (Smoked): May decrease the serum concentration of Nintedanib. Management: Encourage patients to stop smoking prior starting nintedanib therapy and to avoid smoking when using nintedanib. Risk D: Consider therapy modification
A pregnancy test is required prior to initiating treatment and periodically during treatment in patients who may become pregnant. Patients who may become pregnant should use highly effective contraception during therapy and for ≥3 months after the last dose. Patients experiencing vomiting and/or diarrhea during treatment may have decreased efficacy if an oral hormonal contraceptive is used; an alternate form of highly effective contraception may be required in patients with conditions where drug absorption may be reduced.
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.
It is not known if nintedanib is present in breast milk.
Due to the potential for serious adverse reactions in the breastfeeding infant, breastfeeding is not recommended by the manufacturer.
Obtain pregnancy test prior to treatment and periodically during treatment in patients who may become pregnant; obtain LFTs prior to initiation of treatment, at regular intervals during the first 3 months of treatment, and periodically thereafter or as clinically indicated; consider baseline and periodic protein/creatinine ratio in patients at risk of proteinuria. Monitor for GI events (eg, diarrhea, nausea, vomiting, weight loss), arterial thromboembolic events, bleeding, and GI perforation.
Nintedanib 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
Protein binding: ~98%
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).
Bioavailability: ~5%
Half-life elimination: 9.5 hours
Time to peak, plasma: 2 hours (4 hours with food)
Excretion: Feces (~93%); urine (<1%)
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.
Cigarette smoking: Exposure was 21% lower in smokers.
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