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PATIENT SUBGROUPS

A post hoc subgroup analysis in patients with ≤90% and >90% FVC predicted at baseline1

Objective and methods1

  • A post hoc subgroup analysis of pooled data from the INPULSIS® trials was used to evaluate the treatment effect (annual rate of FVC decline) of OFEV (nintedanib) in patients with FVC ≤90% predicted compared to those with FVC >90% predicted at baseline

In the pooled INPULSIS® population (OFEV and placebo arms):

Proportion of patients with FVC predicted at baseline in the pool INPULSIS® population Proportion of patients with FVC predicted at baseline in the pool INPULSIS® population

Annual rate of FVC decline results from a post hoc subgroup analysis of the pooled INPULSIS® trials1

Annual rate of FVC decline results from a post hoc subgroup analysis of the pooled INPULSIS® trials Annual rate of FVC decline results from a post hoc subgroup analysis of the pooled INPULSIS® trials
  • Placebo-treated patients with a baseline FVC >90% predicted declined at a similar rate to patients with a baseline FVC ≤90% predicted over 52 weeks (-225 mL/year vs -224 mL/year, respectively)1
  • The treatment effect was not different between patients with FVC ≤90% predicted and those with FVC >90% predicted, as indicated by the nonsignificant treatment-by-subgroup interaction (P=.530)1
  • Both subgroups had a similar adverse events profile1

Limitations

  • This is a post hoc subgroup analysis. Results are exploratory in nature and cannot be used to demonstrate statistical differences between treatment groups2
In a subgroup analysis, OFEV reduced the annual rate of FVC decline in patients with FVC ≤90% and >90% predicted at baseline1

A prespecified subgroup analysis in patients with ≤70% and >70% FVC predicted at baseline2

Objective and methods

  • A prespecified subgroup analysis of pooled data from the INPULSIS® trials was used to evaluate the treatment effect (annual rate of FVC decline) of OFEV in patients with FVC ≤70% predicted compared to those with FVC >70% predicted at baseline2

In the pooled INPULSIS® population (OFEV and placebo arms)2:

OFEV® INPULSIS® clinical trials FVC predicted at 70 percent OFEV® INPULSIS® clinical trials FVC predicted at 70 percent

Annual rate of FVC decline results from a prespecified subgroup analysis of the pooled INPULSIS® trials2

OFEV® FVC decline 70 percent baseline OFEV® FVC decline 70 percent baseline
  • Placebo-treated patients with a baseline FVC >70% predicted declined at a similar rate to patients with a baseline FVC ≤70% predicted over 52 weeks (-220 mL/year vs -233 mL/year, respectively)2
  • The treatment effect was not different between patients with FVC ≤70% predicted and those with FVC >70% predicted, as indicated by the nonsignificant treatment-by-subgroup interaction (P=.9505)2

Limitations

  • This is a prespecified subgroup analysis. Results are exploratory in nature and cannot be used to demonstrate statistical differences between treatment groups2
In a subgroup analysis, OFEV reduced the annual rate of FVC decline in patients with FVC ≤70% and >70% predicted at baseline2

A post hoc subgroup analysis in patients with and without concomitant emphysema2

Objective and methods2,3

  • A post hoc subgroup analysis of pooled data from the INPULSIS® trials to evaluate the treatment effect (annual rate of FVC decline) in patients with or without emphysema on HRCT at baseline. Concomitant centrilobular emphysema was diagnosed on HRCT based on qualitative assessment

In the pooled INPULSIS® population (OFEV and placebo arms)2:

INPULSIS® clinical trials FVC predicted emphysema INPULSIS® clinical trials FVC predicted emphysema

Annual rate of FVC decline results from a POST HOC subgroup analysis of the pooled INPULSIS® trials2

OFEV® FVC decline emphysema HRCT baseline OFEV® FVC decline emphysema HRCT baseline
  • Placebo-treated patients with concomitant emphysema declined at a similar rate to patients without emphysema over 52 weeks (-207 mL/year vs -234 mL/year, respectively)2
  • The treatment effect of OFEV on the annual rate of FVC decline was not different between patients with or without emphysema on HRCT at baseline, as indicated by the nonsignificant treatment-by-subgroup interaction (P=.5199)2
  • Both subgroups had a similar adverse events profile2

Limitations

  • This is a post hoc subgroup analysis. Results are exploratory in nature and cannot be used to demonstrate statistical differences between treatment groups2
In a subgroup analysis, OFEV reduced the annual rate of FVC decline independent of the presence of emphysema at baseline2

A post hoc subgroup analysis in patients with honeycombing on HRCT and/or biopsy confirmation and those without either4

Objective and methods4

  • A post hoc subgroup analysis of pooled data from the INPULSIS® trials was conducted to evaluate the treatment effect (annual rate of FVC decline) of OFEV in patients with honeycombing on HRCT and/or confirmation of UIP pattern by SLB versus patients without either

In the pooled INPULSIS® population (OFEV and placebo arms)4:

OFEV INPULSIS population with honeycombing on HCRT OFEV INPULSIS population with honeycombing on HCRT

Annual rate of FVC decline results from a POST HOC subgroup analysis of the pooled INPULSIS® trials4

OFEV INPULSIS Honeycombing annual rate of FVC decline OFEV INPULSIS Honeycombing annual rate of FVC decline
  • Placebo-treated patients with honeycombing on HRCT and/or confirmed UIP pattern by SLB declined at a similar rate over 52 weeks to patients without honeycombing on HRCT or SLB (-226 mL/year vs -221 mL/year, respectively)4
  • The treatment effect of OFEV on the annual rate of FVC decline was not different between patients with honeycombing on HRCT and/or SLB confirmation of UIP pattern and patients without either, as indicated by the nonsignificant treatment-by-subgroup interaction (P=.8139)4
  • Both subgroups had a similar adverse events profile4

Limitations

  • This is a post hoc subgroup analysis. Results are exploratory in nature and cannot be used to demonstrate statistical differences between treatment groups2
OFEV reduced the annual rate of FVC decline independent of honeycombing on HRCT and/or biopsy confirmation4

A post hoc subgroup analysis in patients at GAP stage I and patients at GAP stage II/III2

Objective and methods4

  • A post hoc subgroup analysis of pooled data from the INPULSIS® trials was conducted to evaluate the treatment effect (annual rate of FVC decline) of OFEV in patients at GAP stage I at baseline versus GAP stage II/III at baseline
GAP Staging System

In the pooled INPULSIS® population (OFEV and placebo arms)2:

OFEV INPULSIS population at GAP stage 1 OFEV INPULSIS population at GAP stage 1

Annual rate of FVC decline results from a POST HOC subgroup analysis of the pooled INPULSIS® trials2

OFEV INPULSIS GAP Stage 1 annual rate of FVC decline OFEV INPULSIS GAP Stage 1 annual rate of FVC decline
  • Placebo-treated patients at GAP stage I at baseline declined in a similar rate over 52 weeks to patients at GAP stage II/III at baseline (-219 mL/year vs -228 mL/year, respectively)2
  • The treatment effect of OFEV on the annual rate of FVC decline was not different between patients at GAP stage I compared with GAP stage II/III, as indicated by the nonsignificant treatment-by-subgroup interaction (P=.8847)2
  • Adverse events in both subgroups were consistent with the overall safety population2,3

Limitations

  • This is a post hoc subgroup analysis. Results are exploratory in nature and cannot be used to demonstrate statistical differences between treatment groups2
OFEV reduced the annual rate of FVC decline independent of GAP stage2

CI, confidence interval; DLCO, diffusing capacity for carbon monoxide; FVC, forced vital capacity; GAP, gender age physiology; HRCT, high-resolution computed tomography; SLB, surgical lung biopsy; UIP, usual interstitial pneumonia.

IMPORTANT SAFETY INFORMATION

INDICATIONS

IMPORTANT SAFETY INFORMATION

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.

INDICATIONS

OFEV is indicated for the treatment of idiopathic pulmonary fibrosis (IPF).

OFEV is indicated to slow the rate of decline in pulmonary function in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD).

Elevated Liver Enzymes and Drug-Induced Liver Injury

  • Cases of drug-induced liver injury (DILI) have been observed with OFEV treatment. In the clinical trials and post-marketing period, non-serious and serious cases of DILI were reported. Cases of severe liver injury with fatal outcome have been reported in the post-marketing period. The majority of hepatic events occur within the first three months of 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 in the majority of cases.
  • In IPF studies, the majority (94%) of patients with ALT and/or AST elevations had elevations less than 5 times ULN and the majority (95%) of patients with bilirubin elevations had elevations less than 2 times ULN.
  • In the SSc-ILD study, a maximum ALT and/or AST greater than or equal to 3 times ULN was observed in 4.9% of patients treated with OFEV.
  • Patients with low body weight (less than 65 kg), patients who are 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 initiation of treatment, at regular intervals during the first three months of treatment, and periodically thereafter or as clinically indicated. Measure liver function tests promptly in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. Dosage modifications, interruption, or discontinuation may be necessary for liver enzyme elevations.

Gastrointestinal Disorders

Diarrhea

  • In IPF studies, 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 in 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 less than 1% in placebo patients, respectively.
  • In the SSc-ILD study, diarrhea was the most frequent gastrointestinal event reported in 76% versus 32% of patients treated with OFEV and placebo, respectively. Events were primarily mild to moderate in intensity and occurred within the first 3 months. Diarrhea led to permanent dose reduction in 22% and discontinuation in 7% of OFEV patients versus 1% and 0.3% 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

  • In IPF studies, 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.
  • In the SSc-ILD study, nausea was reported in 32% versus 14% and vomiting was reported in 25% versus 10% 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 highly effective contraception during treatment and at least 3 months after the last dose of OFEV. As the impact of nintedanib on the effectiveness of hormonal contraception is unknown, advise women using hormonal contraceptives to add a barrier method. Verify pregnancy status prior to starting OFEV and during treatment as appropriate.

Arterial Thromboembolic Events

  • In IPF studies, 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.
  • In the SSc-ILD study, arterial thromboembolic events were reported in 0.7% of patients in both the OFEV-treated and placebo-treated patients. There were 0 cases of myocardial infarction in OFEV-treated patients compared to 0.7% of placebo-treated 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.
  • In IPF studies, bleeding events were reported in 10% of OFEV versus 7% of placebo patients. In the post-marketing period, non-serious and serious bleeding events, some of which were fatal, have been observed.
  • In the SSc-ILD study, bleeding events were reported in 11% of OFEV versus 8% 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.
  • In IPF studies, gastrointestinal perforation was reported in 0.3% of OFEV versus in 0% placebo patients.
  • In the SSc-ILD study, no cases of gastrointestinal perforation were reported in either OFEV or placebo-treated patients.
  • In the post-marketing period, cases of gastrointestinal perforations have been reported, some of which were fatal. Use caution when treating patients who have had recent abdominal surgery, have a previous history of diverticular disease, or who are receiving concomitant corticosteroids or NSAIDs. 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 greater than or equal to 5% of OFEV patients, and more than placebo, included diarrhea, nausea, vomiting, skin ulcer, abdominal pain, liver enzyme elevation, weight decreased, fatigue, decreased appetite, headache, pyrexia, back pain, dizziness and hypertension.
  • In IPF studies, the most frequent serious adverse reactions reported in patients treated with OFEV, more than placebo, were bronchitis (1.2% vs. 0.8%) and myocardial infarction (1.5% vs. 0.4%). 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.
  • In the SSc-ILD study, the most frequent serious adverse events reported in patients treated with OFEV, more than placebo, were interstitial lung disease (2.4% vs. 1.7%) and pneumonia (2.8% vs. 0.3%). Within 52 weeks, 5 patients treated with OFEV (1.7%) and 4 patients treated with placebo (1.4%) died. There was no pattern among adverse events leading to death in either treatment arm.

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.
CL-OF-100025 09.06.19

Click here for full Prescribing Information, including Patient Information.

References:

  1. Kolb M et al. Thorax. 2017;72(4):340-346.
  2. Data on file. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.
  3. Richeldi L et al; for the INPULSIS Trial Investigators. N Engl J Med. 2014;370(22):2071-2082.
  4. Raghu G et al. Am J Respir Crit Care Med. 2017;195(1):78-85.
  5. Ley B et al. Ann Intern Med. 2012;156(10):684-691.

IMPORTANT SAFETY INFORMATION

INDICATIONS

IMPORTANT SAFETY INFORMATION

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.

INDICATIONS

OFEV is indicated for the treatment of idiopathic pulmonary fibrosis (IPF).

OFEV is indicated to slow the rate of decline in pulmonary function in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD).

Elevated Liver Enzymes and Drug-Induced Liver Injury

  • Cases of drug-induced liver injury (DILI) have been observed with OFEV treatment. In the clinical trials and post-marketing period, non-serious and serious cases of DILI were reported. Cases of severe liver injury with fatal outcome have been reported in the post-marketing period. The majority of hepatic events occur within the first three months of 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 in the majority of cases.
  • In IPF studies, the majority (94%) of patients with ALT and/or AST elevations had elevations less than 5 times ULN and the majority (95%) of patients with bilirubin elevations had elevations less than 2 times ULN.
  • In the SSc-ILD study, a maximum ALT and/or AST greater than or equal to 3 times ULN was observed in 4.9% of patients treated with OFEV.
  • Patients with low body weight (less than 65 kg), patients who are 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 initiation of treatment, at regular intervals during the first three months of treatment, and periodically thereafter or as clinically indicated. Measure liver function tests promptly in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. Dosage modifications, interruption, or discontinuation may be necessary for liver enzyme elevations.

Gastrointestinal Disorders

Diarrhea

  • In IPF studies, 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 in 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 less than 1% in placebo patients, respectively.
  • In the SSc-ILD study, diarrhea was the most frequent gastrointestinal event reported in 76% versus 32% of patients treated with OFEV and placebo, respectively. Events were primarily mild to moderate in intensity and occurred within the first 3 months. Diarrhea led to permanent dose reduction in 22% and discontinuation in 7% of OFEV patients versus 1% and 0.3% 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

  • In IPF studies, 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.
  • In the SSc-ILD study, nausea was reported in 32% versus 14% and vomiting was reported in 25% versus 10% 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 highly effective contraception during treatment and at least 3 months after the last dose of OFEV. As the impact of nintedanib on the effectiveness of hormonal contraception is unknown, advise women using hormonal contraceptives to add a barrier method. Verify pregnancy status prior to starting OFEV and during treatment as appropriate.

Arterial Thromboembolic Events

  • In IPF studies, 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.
  • In the SSc-ILD study, arterial thromboembolic events were reported in 0.7% of patients in both the OFEV-treated and placebo-treated patients. There were 0 cases of myocardial infarction in OFEV-treated patients compared to 0.7% of placebo-treated 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.
  • In IPF studies, bleeding events were reported in 10% of OFEV versus 7% of placebo patients. In the post-marketing period, non-serious and serious bleeding events, some of which were fatal, have been observed.
  • In the SSc-ILD study, bleeding events were reported in 11% of OFEV versus 8% 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.
  • In IPF studies, gastrointestinal perforation was reported in 0.3% of OFEV versus in 0% placebo patients.
  • In the SSc-ILD study, no cases of gastrointestinal perforation were reported in either OFEV or placebo-treated patients.
  • In the post-marketing period, cases of gastrointestinal perforations have been reported, some of which were fatal. Use caution when treating patients who have had recent abdominal surgery, have a previous history of diverticular disease, or who are receiving concomitant corticosteroids or NSAIDs. 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 greater than or equal to 5% of OFEV patients, and more than placebo, included diarrhea, nausea, vomiting, skin ulcer, abdominal pain, liver enzyme elevation, weight decreased, fatigue, decreased appetite, headache, pyrexia, back pain, dizziness and hypertension.
  • In IPF studies, the most frequent serious adverse reactions reported in patients treated with OFEV, more than placebo, were bronchitis (1.2% vs. 0.8%) and myocardial infarction (1.5% vs. 0.4%). 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.
  • In the SSc-ILD study, the most frequent serious adverse events reported in patients treated with OFEV, more than placebo, were interstitial lung disease (2.4% vs. 1.7%) and pneumonia (2.8% vs. 0.3%). Within 52 weeks, 5 patients treated with OFEV (1.7%) and 4 patients treated with placebo (1.4%) died. There was no pattern among adverse events leading to death in either treatment arm.

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.
CL-OF-100025 09.06.19

Click here for full Prescribing Information, including Patient Information.