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2015 ATS/ERS/JRS/ALAT Guidelines recommend* OFEV for the treatment of IPF1

Slows IPF progression

OFEV significantly2-6:
  • Reduced the annual rate of FVC decline in 3 trials
  • Reduced the risk of time to first acute IPF exacerbation over 52 weeks in 2 out of 3 trials

See results

Demonstrated safety profile

Safety and tolerability
profile was demonstrated
in 3 clinical trials2

View safety data

Twice-daily oral dosing

Recommended dosage of one capsule, twice daily with food2†

Learn more


*This is a conditional recommendation. This means that different choices will be appropriate for each patient based on individual preferences.1

†In patients with mild hepatic impairment (Child Pugh A), the recommended dosage is 100 mg twice daily with food.2


ALAT, Latin American Thoracic Association; ATS, American Thoracic Society; ERS, European Respiratory Society; FVC, forced vital capacity; IPF, idiopathic pulmonary fibrosis; JRS, Japanese Respiratory Society; MOA, mechanism of action.

IMPORTANT SAFETY INFORMATION AND INDICATION

WARNINGS AND PRECAUTIONS

Hepatic Impairment

  • OFEV is not recommended in patients with moderate (Child Pugh B) or severe (Child Pugh C) hepatic impairment. Patients with mild hepatic impairment (Child Pugh A) can be treated with a reduced dosage (100 mg twice daily). Consider treatment interruption or discontinuation for management of adverse reactions.

Elevated Liver Enzymes

  • Cases of drug-induced liver injury have been observed with OFEV treatment. OFEV was associated with elevations of liver enzymes (ALT, AST, ALKP, and GGT) and bilirubin. Liver enzyme and bilirubin increases were reversible with dose modification or interruption. The majority (94%) of patients with ALT and/or AST elevations had elevations <5 times ULN. The majority (95%) of patients with bilirubin elevations had elevations <2 times ULN.
  • Patients with a low body weight (<65 kg), Asian, and female patients may have a higher risk of elevations in liver enzymes. Nintedanib exposure increased with patient age, which may result in increased liver enzymes.
  • Conduct liver function tests prior to treatment, then as clinically indicated. Monitor for adverse reactions and consider dosage modifications, interruption, or discontinuation as necessary for liver enzyme elevations. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment, promptly interrupt therapy.

Gastrointestinal Disorders

Diarrhea

  • Diarrhea was the most frequent gastrointestinal event reported in 62% versus 18% of patients treated with OFEV and placebo, respectively. Events were primarily mild to moderate intensity and occurred within the first 3 months. Diarrhea led to permanent dose reduction in 11% and discontinuation in 5% of OFEV patients versus 0 and <1% in placebo patients, respectively.
  • Dosage modifications or treatment interruptions may be necessary in patients with diarrhea. Treat diarrhea at first signs with adequate hydration and antidiarrheal medication (e.g., loperamide), and consider treatment interruption if diarrhea continues. OFEV treatment may be resumed at the full dosage (150 mg twice daily), or at the reduced dosage (100 mg twice daily), which subsequently may be increased to the full dosage. If severe diarrhea persists, discontinue treatment.

Nausea and Vomiting

  • Nausea was reported in 24% versus 7% and vomiting was reported in 12% versus 3% of patients treated with OFEV and placebo, respectively. Events were primarily of mild to moderate intensity. Nausea and vomiting led to discontinuation of OFEV in 2% and 1% of patients, respectively.
  • If nausea or vomiting persists despite appropriate supportive care including anti-emetic therapy, consider dose reduction or treatment interruption. OFEV treatment may be resumed at full dosage or at reduced dosage, which subsequently may be increased to full dosage. If severe nausea or vomiting does not resolve, discontinue treatment.

Embryofetal Toxicity: OFEV can cause fetal harm when administered to a pregnant woman and patients should be advised of the potential risk to a fetus. Women should be advised to avoid becoming pregnant while receiving OFEV and to use effective contraception during treatment and at least 3 months after the last dose of OFEV. Verify pregnancy status prior to starting OFEV.

Arterial Thromboembolic Events: Arterial thromboembolic events were reported in 2.5% of OFEV and 0.8% of placebo patients, respectively. Myocardial infarction was the most common arterial thromboembolic event, occurring in 1.5% of OFEV and 0.4% of placebo patients. Use caution when treating patients at higher cardiovascular risk including known coronary artery disease. Consider treatment interruption in patients who develop signs or symptoms of acute myocardial ischemia.

Risk of Bleeding: OFEV may increase the risk of bleeding. Bleeding events were reported in 10% of OFEV versus 7% of placebo patients. Use OFEV in patients with known risk of bleeding only if the anticipated benefit outweighs the potential risk.

Gastrointestinal Perforation: OFEV may increase the risk of gastrointestinal perforation. Gastrointestinal perforation was reported in 0.3% of OFEV versus in 0% placebo patients. Use caution when treating patients who have had recent abdominal surgery. Discontinue therapy with OFEV in patients who develop gastrointestinal perforation. Only use OFEV in patients with known risk of gastrointestinal perforation if the anticipated benefit outweighs the potential risk.

ADVERSE REACTIONS

  • Adverse reactions reported in ≥5% of OFEV patients included diarrhea, nausea, abdominal pain, liver enzyme elevation, vomiting, decreased appetite, weight decreased, headache, and hypertension.
  • The most frequent serious adverse reactions reported in OFEV patients were bronchitis and myocardial infarction. The most common adverse events leading to death in OFEV patients versus placebo were pneumonia (0.7% vs. 0.6%), lung neoplasm malignant (0.3% vs. 0%), and myocardial infarction (0.3% vs. 0.2%). In the predefined category of major adverse cardiovascular events (MACE) including MI, fatal events were reported in 0.6% of OFEV versus 1.8% in placebo patients.

DRUG INTERACTIONS

  • P-glycoprotein (P-gp) and CYP3A4 Inhibitors and Inducers: Coadministration with oral doses of a P-gp and CYP3A4 inhibitor, ketoconazole, increased exposure to nintedanib by 60%. Concomitant use of potent P-gp and CYP3A4 inhibitors (e.g., erythromycin) with OFEV may increase exposure to nintedanib. In such cases, patients should be monitored closely for tolerability of OFEV. Management of adverse reactions may require interruption, dose reduction, or discontinuation of therapy with OFEV. Coadministration with oral doses of a P-gp and CYP3A4 inducer, rifampicin, decreased exposure to nintedanib by 50%. Concomitant use of P-gp and CYP3A4 inducers (e.g., carbamazepine, phenytoin, and St. John’s wort) with OFEV should be avoided as these drugs may decrease exposure to nintedanib.
  • Anticoagulants: Nintedanib may increase the risk of bleeding. Monitor patients on full anticoagulation therapy closely for bleeding and adjust anticoagulation treatment as necessary.

USE IN SPECIFIC POPULATIONS

  • Nursing Mothers: Because of the potential for serious adverse reactions in nursing infants from OFEV, advise women that breastfeeding is not recommended during treatment.
  • Reproductive Potential: OFEV may reduce fertility in females of reproductive potential.
  • Smokers: Smoking was associated with decreased exposure to OFEV, which may affect the efficacy of OFEV. Encourage patients to stop smoking prior to and during treatment.
OFEVPROFISIAUG2017

Indication

OFEV (nintedanib) is indicated for the treatment of Idiopathic Pulmonary Fibrosis (IPF).

Click here for full Prescribing Information, including Patient Information.

References

1. Raghu G, Rochwerg B, Zhang Y, et al; on behalf of the ATS, ERS, JRS, and ALAT. An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis: an executive summary. An update of the 2011 clinical practice guideline. Am J Respir Crit Care Med. 2015;192(2):e3-e19. 2. OFEV® (nintedanib) Prescribing Information. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2017. 3. Zappala CJ, Latsi PI, Nicholson AG, et al. Marginal decline in forced vital capacity is associated with a poor outcome in idiopathic pulmonary fibrosis. Eur Respir J. 2010;35(4):830-836. 4. Schmidt SL, Tayob N, Han MK, et al. Predicting pulmonary fibrosis disease course from past trends in pulmonary function. Chest. 2014;145(3):579-585. 5. du Bois RM, Weycker D, Albera C, et al. Forced vital capacity in patients with idiopathic pulmonary fibrosis: test properties and minimal clinically important difference. Am J Respir Crit Care Med. 2011;184(12):1382-1389. 6. Song JW, Hong S-B, Lim C-M, Koh Y, Kim DS. Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors and outcome. Eur Respir J. 2011;37(2):356-363.

IMPORTANT SAFETY INFORMATION AND INDICATION

WARNINGS AND PRECAUTIONS

Hepatic Impairment

  • OFEV is not recommended in patients with moderate (Child Pugh B) or severe (Child Pugh C) hepatic impairment. Patients with mild hepatic impairment (Child Pugh A) can be treated with a reduced dosage (100 mg twice daily). Consider treatment interruption or discontinuation for management of adverse reactions.

Elevated Liver Enzymes

  • Cases of drug-induced liver injury have been observed with OFEV treatment. OFEV was associated with elevations of liver enzymes (ALT, AST, ALKP, and GGT) and bilirubin. Liver enzyme and bilirubin increases were reversible with dose modification or interruption. The majority (94%) of patients with ALT and/or AST elevations had elevations <5 times ULN. The majority (95%) of patients with bilirubin elevations had elevations <2 times ULN.
  • Patients with a low body weight (<65 kg), Asian, and female patients may have a higher risk of elevations in liver enzymes. Nintedanib exposure increased with patient age, which may result in increased liver enzymes.
  • Conduct liver function tests prior to treatment, then as clinically indicated. Monitor for adverse reactions and consider dosage modifications, interruption, or discontinuation as necessary for liver enzyme elevations. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment, promptly interrupt therapy.

Gastrointestinal Disorders

Diarrhea

  • Diarrhea was the most frequent gastrointestinal event reported in 62% versus 18% of patients treated with OFEV and placebo, respectively. Events were primarily mild to moderate intensity and occurred within the first 3 months. Diarrhea led to permanent dose reduction in 11% and discontinuation in 5% of OFEV patients versus 0 and <1% in placebo patients, respectively.
  • Dosage modifications or treatment interruptions may be necessary in patients with diarrhea. Treat diarrhea at first signs with adequate hydration and antidiarrheal medication (e.g., loperamide), and consider treatment interruption if diarrhea continues. OFEV treatment may be resumed at the full dosage (150 mg twice daily), or at the reduced dosage (100 mg twice daily), which subsequently may be increased to the full dosage. If severe diarrhea persists, discontinue treatment.

Nausea and Vomiting

  • Nausea was reported in 24% versus 7% and vomiting was reported in 12% versus 3% of patients treated with OFEV and placebo, respectively. Events were primarily of mild to moderate intensity. Nausea and vomiting led to discontinuation of OFEV in 2% and 1% of patients, respectively.
  • If nausea or vomiting persists despite appropriate supportive care including anti-emetic therapy, consider dose reduction or treatment interruption. OFEV treatment may be resumed at full dosage or at reduced dosage, which subsequently may be increased to full dosage. If severe nausea or vomiting does not resolve, discontinue treatment.

Embryofetal Toxicity: OFEV can cause fetal harm when administered to a pregnant woman and patients should be advised of the potential risk to a fetus. Women should be advised to avoid becoming pregnant while receiving OFEV and to use effective contraception during treatment and at least 3 months after the last dose of OFEV. Verify pregnancy status prior to starting OFEV.

Arterial Thromboembolic Events: Arterial thromboembolic events were reported in 2.5% of OFEV and 0.8% of placebo patients, respectively. Myocardial infarction was the most common arterial thromboembolic event, occurring in 1.5% of OFEV and 0.4% of placebo patients. Use caution when treating patients at higher cardiovascular risk including known coronary artery disease. Consider treatment interruption in patients who develop signs or symptoms of acute myocardial ischemia.

Risk of Bleeding: OFEV may increase the risk of bleeding. Bleeding events were reported in 10% of OFEV versus 7% of placebo patients. Use OFEV in patients with known risk of bleeding only if the anticipated benefit outweighs the potential risk.

Gastrointestinal Perforation: OFEV may increase the risk of gastrointestinal perforation. Gastrointestinal perforation was reported in 0.3% of OFEV versus in 0% placebo patients. Use caution when treating patients who have had recent abdominal surgery. Discontinue therapy with OFEV in patients who develop gastrointestinal perforation. Only use OFEV in patients with known risk of gastrointestinal perforation if the anticipated benefit outweighs the potential risk.

ADVERSE REACTIONS

  • Adverse reactions reported in ≥5% of OFEV patients included diarrhea, nausea, abdominal pain, liver enzyme elevation, vomiting, decreased appetite, weight decreased, headache, and hypertension.
  • The most frequent serious adverse reactions reported in OFEV patients were bronchitis and myocardial infarction. The most common adverse events leading to death in OFEV patients versus placebo were pneumonia (0.7% vs. 0.6%), lung neoplasm malignant (0.3% vs. 0%), and myocardial infarction (0.3% vs. 0.2%). In the predefined category of major adverse cardiovascular events (MACE) including MI, fatal events were reported in 0.6% of OFEV versus 1.8% in placebo patients.

DRUG INTERACTIONS

  • P-glycoprotein (P-gp) and CYP3A4 Inhibitors and Inducers: Coadministration with oral doses of a P-gp and CYP3A4 inhibitor, ketoconazole, increased exposure to nintedanib by 60%. Concomitant use of potent P-gp and CYP3A4 inhibitors (e.g., erythromycin) with OFEV may increase exposure to nintedanib. In such cases, patients should be monitored closely for tolerability of OFEV. Management of adverse reactions may require interruption, dose reduction, or discontinuation of therapy with OFEV. Coadministration with oral doses of a P-gp and CYP3A4 inducer, rifampicin, decreased exposure to nintedanib by 50%. Concomitant use of P-gp and CYP3A4 inducers (e.g., carbamazepine, phenytoin, and St. John’s wort) with OFEV should be avoided as these drugs may decrease exposure to nintedanib.
  • Anticoagulants: Nintedanib may increase the risk of bleeding. Monitor patients on full anticoagulation therapy closely for bleeding and adjust anticoagulation treatment as necessary.

USE IN SPECIFIC POPULATIONS

  • Nursing Mothers: Because of the potential for serious adverse reactions in nursing infants from OFEV, advise women that breastfeeding is not recommended during treatment.
  • Reproductive Potential: OFEV may reduce fertility in females of reproductive potential.
  • Smokers: Smoking was associated with decreased exposure to OFEV, which may affect the efficacy of OFEV. Encourage patients to stop smoking prior to and during treatment.
OFEVPROFISIAUG2017

INDICATION

OFEV (nintedanib) is indicated for the treatment of Idiopathic Pulmonary Fibrosis (IPF).

Click here for full Prescribing Information, including Patient Information.
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