Medical Editor: John P. Cunha, DO, FACOEP
What Is Ofev?
Ofev (nintedanib) is a kinase inhibitor used to treat idiopathic pulmonary fibrosis (IPF).
What Are Side Effects of Ofev?
Ofev may cause serious side effects including:
- hives,
- difficulty breathing,
- swelling of your face, lips, tongue, or throat,
- chest, jaw, and left arm pain,
- unusual sweating,
- weakness on one side of the body,
- sudden vision problems,
- trouble speaking,
- sudden severe back pain,
- headache,
- severe abdominal pain,
- abdominal swelling, and
- severe dizziness
Get medical help right away, if you have any of the symptoms listed above.
Common side effects of Ofev include:
- diarrhea,
- nausea,
- stomach or abdominal pain,
- vomiting,
- liver problems and liver enzyme elevation,
- decreased appetite,
- headache,
- weight loss, and
- high blood pressure (hypertension)
Seek medical care or call 911 at once if you have the following serious side effects:
- Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
- Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; and sudden dizziness, lightheadedness, or passing out;
- Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.
Dosage for Ofev
The recommended dosage of Ofev is 150 mg twice daily administered approximately 12 hours apart.
What Drugs, Substances, or Supplements Interact with Ofev?
Ofev may interact with:
- ketoconazole,
- rifampicin,
- carbamazepine,
- phenytoin,
- St. John's wort, and
- anticoagulants
Tell your doctor all medications and supplements you use.
Ofev During Pregnancy and Breastfeeding
Women should not become pregnant while taking Ofev. It can cause birth defects or death to an unborn baby. Women should use birth control during treatment and for at least 3 months after treatment. If you become pregnant while taking Ofev, tell your doctor right away. Breastfeeding is not recommended while using this drug.
Additional Information
Our Ofev (nintedanib) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
SLIDESHOW
COPD Foods to Boost Your Health - COPD Diet Tips See SlideshowGet emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Call your doctor at once if you have:
- severe ongoing nausea, vomiting, or diarrhea;
- severe stomach pain, bloating, or tenderness;
- bleeding from your rectum or blood in your stools;
- easy bruising or bleeding, any wound that will not heal;
- fever, chills, cough with mucus, chest pain, feeling short of breath;
- heart attack symptoms--chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating;
- liver problems--stomach pain (upper right side), loss of appetite, tiredness, dark urine, jaundice (yellowing of the skin or eyes); or
- signs of a stroke--sudden numbness or weakness (especially on one side of the body), slurred speech, problems with vision or balance.
Liver problems may be more likely in women, in people who weigh less than 143 pounds (65 kilograms), and in people of Asian descent.
Your doses may be delayed if you have certain side effects.
Common side effects may include:
- nausea, vomiting, loss of appetite;
- stomach pain;
- diarrhea, weight loss;
- increased blood pressure;
- headache; or
- abnormal liver function tests.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
QUESTION
COPD (chronic obstructive pulmonary disease) is the same as adult-onset asthma. See AnswerSIDE EFFECTS
The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling:
- Elevated Liver Enzymes and Drug-Induced Liver Injury [see WARNINGS AND PRECAUTIONS]
- Gastrointestinal Disorders [see WARNINGS AND PRECAUTIONS]
- Embryo-Fetal Toxicity [see WARNINGS AND PRECAUTIONS]
- Arterial Thromboembolic Events [see WARNINGS AND PRECAUTIONS]
- Risk of Bleeding [see WARNINGS AND PRECAUTIONS]
- Gastrointestinal Perforation [see WARNINGS AND PRECAUTIONS]
- Nephrotic Range Proteinuria [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of OFEV was evaluated in over 1000 IPF patients, 332 patients with chronic fibrosing ILDs with a progressive phenotype, and over 280 patients with SSc-ILD. Over 200 IPF patients were exposed to OFEV for more than 2 years in clinical trials.
Idiopathic Pulmonary Fibrosis
OFEV was studied in three randomized, double-blind, placebo-controlled, 52-week trials. In the phase 2 (Study 1) and phase 3 (Study 2 and Study 3) trials, 723 patients with IPF received OFEV 150 mg twice daily and 508 patients received placebo. The median duration of exposure was 10 months for patients treated with OFEV and 11 months for patients treated with placebo. Subjects ranged in age from 42 to 89 years (median age of 67 years). Most patients were male (79%) and Caucasian (60%).
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 patients treated with OFEV, more than 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-treated patients and 1.8% of placebo-treated patients.
Adverse reactions leading to permanent dose reductions were reported in 16% of OFEV-treated patients and 1% of placebo-treated patients. The most frequent adverse reaction that led to permanent dose reduction in the patients treated with OFEV was diarrhea (11%).
Adverse reactions leading to discontinuation were reported in 21% of OFEV-treated patients and 15% of placebo-treated patients. The most frequent adverse reactions that led to discontinuation in OFEV-treated patients were diarrhea (5%), nausea (2%), and decreased appetite (2%).
The most common adverse reactions with an incidence of greater than or equal to 5% and more frequent in the OFEV than placebo treatment group are listed in Table 1.
Table 1 : Adverse Reactions Occurring in ≥5% of OFEV-treated Patients with Idiopathic Pulmonary Fibrosis and More Commonly Than Placebo in Study 1, Study 2, and Study 3
| Adverse Reaction | OFEV, 150 mg n=723 |
Placebo n=508 |
| Gastrointestinal disorders | ||
| Diarrhea | 62% | 18% |
| Nausea | 24% | 7% |
| Abdominal paina | 15% | 6% |
| Vomiting | 12% | 3% |
| Hepatobiliary disorders | ||
| Liver enzyme elevationb | 14% | 3% |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 11% | 5% |
| Nervous system disorders | ||
| Headache | 8% | 5% |
| Investigations | ||
| Weight decreased | 10% | 3% |
| Vascular disorders | ||
| Hypertensionc | 5% | 4% |
| a Includes abdominal pain, abdominal pain upper, abdominal pain lower, gastrointestinal pain and abdominal tenderness. b Includes gamma-glutamyltransferase increased, hepatic enzyme increased, alanine aminotransferase increased, aspartate aminotransferase increased, hepatic function abnormal, liver function test abnormal, transaminase increased, blood alkaline phosphatase-increased, alanine aminotransferase abnormal, aspartate aminotransferase abnormal, and gamma-glutamyltransferase abnormal. c Includes hypertension, blood pressure increased, hypertensive crisis, and hypertensive cardiomyopathy. |
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In addition, hypothyroidism was reported in patients treated with OFEV, more than placebo (1.1% vs. 0.6%). Alopecia was also reported in more patients treated with OFEV than placebo (0.8% vs. 0.4%).
Combination With Pirfenidone
Concomitant treatment with nintedanib and pirfenidone was investigated in an exploratory open-label, randomized (1:1) trial of nintedanib 150 mg twice daily with add-on pirfenidone (titrated to 801 mg three times a day) compared to nintedanib 150 mg twice daily alone in 105 randomized patients for 12 weeks. The primary endpoint was the percentage of patients with gastrointestinal adverse events from baseline to Week 12. Gastrointestinal adverse events were in line with the established safety profile of each component and were experienced in 37 (70%) patients treated with pirfenidone added to nintedanib versus 27 (53%) patients treated with nintedanib alone.
Diarrhea, nausea, vomiting, and abdominal pain (includes upper abdominal pain, abdominal discomfort, and abdominal pain) were the most frequent adverse events reported in 20 (38%) versus 16 (31%), in 22 (42%) versus 6 (12%), in 15 (28%) versus 6 (12%), and in 15 (28%) versus 7 (14%) patients treated with pirfenidone added to nintedanib versus nintedanib alone, respectively. More subjects reported AST or ALT elevations (greater than or equal to 3x the upper limit of normal) when using pirfenidone in combination with nintedanib (n=3 (6%)) compared to nintedanib alone (n=0) [see WARNINGS AND PRECAUTIONS].
Chronic Fibrosing Interstitial Lung Diseases With A Progressive Phenotype
OFEV was studied in a phase 3, double-blind, placebo-controlled trial (Study 5) in which 663 patients with chronic fibrosing ILDs with a progressive phenotype were randomized to receive OFEV 150 mg twice daily (n=332) or placebo (n=331) for at least 52 weeks. At 52 weeks, the median duration of exposure was 12 months for patients in both treatment arms. Subjects ranged in age from 27 to 87 years (median age of 67 years). The majority of patients were Caucasian (74%) or Asian (25%). Most patients were male (54%).
The most frequent serious adverse event reported in patients treated with OFEV, more than placebo, was pneumonia (4% vs. 3%). Adverse events leading to death were reported in 3% of patients treated with OFEV and in 5% of patients treated with placebo. No pattern was identified in the adverse events leading to death.
Adverse reactions leading to permanent dose reductions were reported in 33% of OFEV-treated patients and 4% of placebo-treated patients. The most frequent adverse reaction that led to permanent dose reduction in the patients treated with OFEV was diarrhea (16%).
Adverse reactions leading to discontinuation were reported in 20% of OFEV-treated patients and 10% of placebo-treated patients. The most frequent adverse reaction that led to discontinuation in OFEV-treated patients was diarrhea (6%).
The safety profile in patients with chronic fibrosing ILDs with a progressive phenotype treated with OFEV was consistent with that observed in IPF patients. In addition, the following adverse events were reported in OFEV more than placebo in chronic progressive fibrosing ILD: nasopharyngitis (13% vs. 12%), upper respiratory tract infection (7% vs 6%), urinary tract infection (6% vs. 4%), fatigue (10% vs. 6%), and back pain (6% vs. 5%).
Systemic Sclerosis-Associated Interstitial Lung Disease
OFEV was studied in a phase 3, randomized, double-blind, placebo-controlled trial (Study 4) in which 576 patients with SSc-ILD received OFEV 150 mg twice daily (n=288) or placebo (n=288). Patients were to receive treatment for at least 52 weeks; individual patients were treated for up to 100 weeks. The median duration of exposure was 15 months for patients treated with OFEV and 16 months for patients treated with placebo. Subjects ranged in age from 20 to 79 years (median age of 55 years). Most patients were female (75%). Patients were mostly Caucasian (67%), Asian (25%), or Black (6%). At baseline, 49% of patients were on stable therapy with mycophenolate.
The most frequent serious adverse events reported in patients treated with OFEV, more than placebo, were interstitial lung disease (2.4% nintedanib vs. 1.7% placebo) and pneumonia (2.8% nintedanib vs. 0.3% placebo). 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.
Adverse reactions leading to permanent dose reductions were reported in 34% of OFEV-treated patients and 4% of placebo-treated patients. The most frequent adverse reaction that led to permanent dose reduction in the patients treated with OFEV was diarrhea (22%).
Adverse reactions leading to discontinuation were reported in 16% of OFEV-treated patients and 9% of placebo-treated patients. The most frequent adverse reactions that led to discontinuation in OFEV-treated patients were diarrhea (7%), nausea (2%), vomiting (1%), abdominal pain (1%), and interstitial lung disease (1%).
The safety profile in patients treated with OFEV with or without mycophenolate at baseline was comparable.
The most common adverse reactions with an incidence of greater than or equal to 5% in OFEV-treated patients and more commonly than in placebo are listed in Table 2.
Table 2 : Adverse Reactions Occurring in ≥5% of OFEV-treated Patients with Systemic Sclerosis- Associated Interstitial Lung Disease and More Commonly Than Placebo in Study 4
| Adverse Reaction | OFEV, 150 mg n=288 |
Placebo n=288 |
| Diarrhea | 76% | 32% |
| Nausea | 32% | 14% |
| Vomiting | 25% | 10% |
| Skin ulcer | 18% | 17% |
| Abdominal paina | 18% | 11% |
| Liver enzyme elevationb | 13% | 3% |
| Weight decreased | 12% | 4% |
| Fatigue | 11% | 7% |
| Decreased appetite | 9% | 4% |
| Headache | 9% | 8% |
| Pyrexia | 6% | 5% |
| Back pain | 6% | 4% |
| Dizziness | 6% | 4% |
| Hypertensionc | 5% | 2% |
| a Includes abdominal pain, abdominal pain upper, abdominal pain lower, and esophageal pain. b Includes alanine aminotransferase increased, gamma-glutamyltransferase increased, aspartate aminotransferase increased, hepatic enzyme increased, blood alkaline phosphatase increased, transaminase increased, and hepatic function abnormal. c Includes hypertension, blood pressure increased, and hypertensive crisis. |
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In addition, alopecia was reported in patients treated with OFEV, more than placebo (1.4% vs. 1.0%).
Postmarketing Experience
The following adverse reactions have been identified during postapproval use of OFEV. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following adverse reactions have been identified during postapproval use of OFEV: drug-induced liver injury [see WARNINGS AND PRECAUTIONS], non-serious and serious bleeding events, some of which were fatal [see WARNINGS AND PRECAUTIONS], proteinuria [see WARNINGS AND PRECAUTIONS], pancreatitis, thrombocytopenia, rash, pruritus.
DRUG INTERACTIONS
P-glycoprotein (P-gp) And CYP3A4 Inhibitors And Inducers
Nintedanib is a substrate of P-gp and, to a minor extent, CYP3A4 [see CLINICAL PHARMACOLOGY]. Coadministration with oral doses of a P-gp and CYP3A4 inhibitor, ketoconazole, increased exposure to nintedanib by 60%. Concomitant use of P-gp and CYP3A4 inhibitors (e.g., erythromycin) with OFEV may increase exposure to nintedanib [see CLINICAL PHARMACOLOGY]. 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 [see DOSAGE AND ADMINISTRATION].
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 [see CLINICAL PHARMACOLOGY].
Anticoagulants
Nintedanib is a VEGFR inhibitor and may increase the risk of bleeding. Monitor patients on full anticoagulation therapy closely for bleeding and adjust anticoagulation treatment as necessary [see WARNINGS AND PRECAUTIONS].
Pirfenidone
In a multiple-dose study conducted to assess the pharmacokinetic effects of concomitant treatment with nintedanib and pirfenidone, the coadministration of nintedanib with pirfenidone did not alter the exposure of either agent [see CLINICAL PHARMACOLOGY]. Therefore, no dose adjustment is necessary during concomitant administration of nintedanib with pirfenidone.
Bosentan
Coadministration of nintedanib with bosentan did not alter the pharmacokinetics of nintedanib [see CLINICAL PHARMACOLOGY].
Read the entire FDA prescribing information for Ofev (Nintedanib Capsules)
© Ofev Patient Information is supplied by Cerner Multum, Inc. and Ofev Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.
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