Ofev

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your body's response to nintedanib.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Ofev is part of the drug class:

• Protein kinase inhibitors

Contraindications

• Manufacturer states none known.1

Warnings/Precautions

Hepatic Toxicity

Abnormal liver function test results reported.1 If hepatic toxicity occurs, temporary interruption, dosage reduction, or discontinuance of therapy may be necessary.1 (See Dosage Modification for Toxicity under Dosage and Administration.)

Perform liver function tests prior to initiation, monthly for the first 3 months, then every 3 months, and as clinically indicated.1

GI Effects

Diarrhea, nausea, and vomiting may occur.1 In clinical studies, diarrhea reported frequently in patients receiving nintedanib and generally occurred within first 3 months of therapy.1 Nausea and vomiting reported less frequently.1

Treat adverse GI effects as necessary with appropriate supportive therapy.1 If diarrhea occurs or if nausea or vomiting persists despite appropriate supportive care, temporary interruption and/or dosage reduction may be necessary.1

Discontinue nintedanib if diarrhea persists despite symptomatic treatment or if severe nausea or vomiting does not resolve.1 (See Dosage Modification for Toxicity under Dosage and Administration.)

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm.1 Embryofetal toxicity and teratogenicity demonstrated in animals.1 Avoid pregnancy during therapy and for at least 3 months after drug discontinuance.1 If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.1 (See Advice to Patients.)

Arterial Thromboembolic Events

Arterial thromboembolic events (e.g., MI) reported.1 Use with caution in patients with cardiovascular risks, including coronary artery disease.1 Consider treatment interruption in patients who develop signs or symptoms of acute myocardial ischemia.1

Hemorrhage

May increase the risk of bleeding based on mechanism of action.1 Use in patients with risk factors for bleeding only if the potential benefit outweighs the risk.1

GI Perforation

May increase the risk of GI perforation based on mechanism of action.1 Use caution in patients with recent abdominal surgery.1 Use in patients with risk factors for GI perforation only if the potential benefit outweighs the risk.1 Discontinue nintedanib if GI perforation develops.1

Specific Populations

Category D.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Distributed into milk in rats; not known whether distributed into human milk.1 Discontinue nursing or the drug.1

Safety and efficacy not established.1

No overall differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1

Not formally studied in patients with hepatic impairment.1 Monitor closely in patients with mild hepatic impairment (Child-Pugh class A).1 Safety and efficacy not established in patients with moderate or severe hepatic impairment (Child-Pugh class B or C).1 (See Hepatic Impairment under Dosage and Administration.)

Systemic exposure to nintedanib not affected by mild or moderate renal impairment (Clcr 30–90 mL/minute); no initial dosage adjustment necessary.1 Safety and efficacy not established in patients with severe renal impairment or end-stage renal disease.1 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Diarrhea,1 nausea,1 abdominal pain,1 elevated concentrations of hepatic enzymes (e.g., ALT, AST, alkaline phosphatase),1 vomiting,1 decreased appetite,1 decreased weight,1 headache,1 hypertension.1

In the U.S.

• Ofev

Available Dosage Forms:

• Capsule

Pharmacologic Class: Tyrosine Kinase Inhibitor

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Diarrhea
• nausea
• severe stomach pain
• vomiting

• Abdominal or stomach pain or swelling
• black, tarry stools
• blood in the urine
• blurred vision
• bruising or purple areas on the skin
• chest pain or discomfort
• coughing up blood
• decreased alertness
• dizziness
• headache
• irregular heartbeat
• joint pain or swelling
• nervousness
• nosebleeds
• pain or discomfort in the arms, jaw, back, or neck
• pain in the chest, groin, or legs, especially calves of the legs
• pounding in the ears
• severe headaches of sudden onset
• shortness of breath
• slow or fast heartbeat
• sudden loss of coordination
• sudden onset of shortness of breath for no apparent reason
• sudden onset of slurred speech
• sudden vision changes
• sweating

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Decreased appetite
• weight loss

• Constipation
• depression
• dry skin and hair
• feeling cold
• hair loss
• hoarseness or husky voice
• muscle cramps and stiffness
• slow heartbeat
• unusual tiredness or weakness
• weight gain

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• If you have an allergy to Ofev (nintedanib) or any part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have liver disease.
• If you are taking any of these drugs: Carbamazepine, phenytoin, rifampin, or St. John's wort.
• If you are breast-feeding. Do not breast-feed while you take Ofev.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Ofev with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
• Signs of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Loose stools (diarrhea) that will not go away.
• Very loose stools (diarrhea).
• Very upset stomach or throwing up.
• This medicine may raise the chance of holes or tears in the stomach or bowels. Call your doctor right away if you have stomach swelling or very bad stomach pain.
• Very bad blood clots like heart attack have happened with this medicine. Call your doctor right away if you have signs of heart attack like chest pain or pressure; arm, back, neck, or jaw pain; or shortness of breath. Call your doctor right away if you have signs of stroke like confusion, numbness or weakness on 1 side of your body, very bad dizziness or headache, or change in speech or eyesight.

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

You should not use Ofev if you are allergic to nintedanib, or if you are pregnant.

To make sure Ofev is safe for you, tell your doctor if you have ever had:

• liver disease;

• heart disease, coronary artery disease (hardened arteries);

• a blood clot;

• kidney disease;

• a bleeding or blood clotting disorder such as hemophilia;

• surgery on your stomach or intestines;

• if you smoke; or

• if you take laxatives, stool softeners, or any medicine or supplements that can cause diarrhea.

Using Ofev during pregnancy could harm the unborn baby. Do not use this medicine if you are pregnant. Use effective birth control to prevent pregnancy while you are using this medicine and for at least 3 months after your last dose.

You may need to have a negative pregnancy test before starting this treatment.

Mintedanib may affect fertility (your ability to have children) in women. Talk to your doctor about your risk.

It is not known whether nintedanib passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using Ofev.

Usual Adult Dose for Idiopathic Pulmonary Fibrosis:

150 mg orally every 12 hours with food

Maximum dose: 300 mg/day

Comments:
-Swallow whole with liquid; do not chew or crush due to bitter taste.
-Advise patient to skip missed dose.

Use: Treatment of idiopathic pulmonary fibrosis.

Smoking can make Ofev less effective. Avoid smoking while taking this medicine, or try to quit before you start this treatment.

Get emergency medical help if you have any signs of an allergic reaction to Ofev: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using Ofev and call your doctor at once if you have:

• severe ongoing nausea, vomiting, or diarrhea;

• chronic cough, chest tightness;

• easy bruising or bleeding (nosebleeds, bleeding gums), any wound that will not heal;

• signs of stomach bleeding - stomach pain or swelling, bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;

• heart attack symptoms - chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating;

• liver problems - stomach pain (upper right side), easy bruising or bleeding, feeling tired, dark urine, clay-colored stools, 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.

Common Ofev side effects may include:

• nausea, vomiting, loss of appetite;

• stomach pain;

• diarrhea;

• weight loss; or

• headache.

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.