Nintedanib

Nintedanib comes as a capsule to take by mouth. It is usually taken with food every 12 hours (twice a day). Take nintedanib capsules at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take nintedanib exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Swallow the capsules whole with liquid; do not chew or crush them.

Your doctor may need to decrease your dose or stop treatment if you experience certain severe side effects. Be sure to tell your doctor how you are feeling during your treatment.

Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

Before taking nintedanib,

• tell your doctor and pharmacist if you are allergic to nintedanib, any other medications, or any of the ingredients in nintedanib capsules. Ask your pharmacist or check the manufacturer's patient information for a list of the ingredients.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: anticoagulants (''blood thinners'') such as warfarin (Coumadin); aspirin; carbamazepine (Carbatrol, Epitol, Equetro, Tegretol, Teril); erythromycin (E.E.S., Ery-Tab, Eryc); ketoconazole; laxatives; phenytoin (Dilantin, Phenytek); pirfenidone (Esbriet); rifampin (Rifadin, Rimactane, in Rifamate, in Rifater); or stool softeners. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor what herbal products you are taking, especially St. John's wort.
• tell your doctor if you or anyone in your family has ever had a bleeding problem, if you have or have ever had liver or heart disease or blood clots, and if you have had recent abdominal surgery.
• tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. You should not become pregnant while you are taking nintedanib; the medication may harm your unborn baby. Talk to your doctor about birth control methods that you can use during your treatment and for at least 3 months after your last dose of nintedanib. If you become pregnant while taking nintedanib, call your doctor.
• tell your doctor if you use tobacco products. Cigarette smoking may decrease the effectiveness of this medication. You should stop smoking before you start taking nintedanib and avoid smoking during your treatment.

If you miss a dose of nintedanib, skip the missed dose and continue your regular schedule. Do not take a double dose to make up for a missed one.

Your doctor will perform blood tests to make sure you do not have conditions that would prevent you from safely using nintedanib.

Nintedanib is usually taken 2 times per day, every 12 hours. Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Take with food and a full glass of water.

Do not crush or chew a nintedanib capsule. Swallow it whole to avoid a bitter taste.

You may be given medication to treat diarrhea or vomiting. Take only the type and amount of medicine your doctor recommends.

Drink plenty of liquids and call your doctor at once if you have diarrhea while taking nintedanib.

You may need frequent medical tests to be sure nintedanib is not causing harmful effects on your liver. Your next few doses may be delayed based on the results of these tests.

Store at room temperature away from moisture and heat.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Oral Administration

Take with food

Swallow capsule whole with liquid; do not chew or crush (bitter taste); effect of crushing on the pharmacokinetics is unknown

If a dose is missed, the next dose should be taken at the next scheduled time; advise the patient to not make up for a missed dose

Not to exceed 300 mg/day

Nintedanib is a prescription medication used to treat a lung disease called idiopathic pulmonary fibrosis (IPF).

Nintedanib belongs to a group of drugs called tyrosine kinase inhibitors. These work by by blocking multiple pathways that may be involved in the scarring of lung tissue.

This medication comes in capsule form and is usually taken twice daily, with food. Swallow capsules whole.

Common side effects of nintedanib include those affecting the stomach such as stomach pain.

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

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

• severe ongoing nausea, vomiting, or diarrhea;

• chronic cough, chest tightness;

• easy bruising or bleeding, 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 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.

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.

Take nintedanib exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

nintedanib should come with a patient information leaflet. Read and follow these instructions carefully. Ask your doctor if you have any questions.

Swallow the capsule whole with liquids. Do not crush, break, or chew it. Take nintedanib with food.

Dosing

The dose of nintedanib will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of nintedanib. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (capsules):
  • For idiopathic pulmonary fibrosis:
    • Adults—150 milligrams (mg) two times a day, taken 12 hours apart.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of nintedanib, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

It is very important that your doctor check your progress at regular visits to make sure nintedanib is working properly. Blood tests may be needed to check for unwanted effects.

Using nintedanib while you are pregnant can harm your unborn baby. Women will receive a pregnancy test before starting nintedanib. Use an effective form of birth control to keep from getting pregnant during treatment and for at least 3 months after the last dose. If you think you have become pregnant while using nintedanib, tell your doctor right away.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow eyes or skin. These could be symptoms of a serious liver problem.

nintedanib may cause diarrhea, and in some cases it can be severe. Do not take any medicine to treat diarrhea without first checking with your doctor. If mild diarrhea continues or gets worse, check with your doctor.

nintedanib may increase your risk of bleeding, or your risk of having a heart attack or stroke. Check with your doctor right away if you have chest pain or discomfort, dizziness, headache, shortness of breath, nausea or vomiting, pain or discomfort in the arms, jaw, back, or neck, sweating, or unusual bleeding or bruising.

nintedanib may cause a tear (perforation) in your stomach or bowels. Check with your doctor right away if you have severe stomach pain that does not go away or blood in the stool.

Stop smoking before treatment with Ofev® and avoid smoking while you are using nintedanib.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.

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.

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 to patients with normal hepatic function.

Cigarette smoking: Exposure was 21% lower in smokers.

>10%:

Gastrointestinal: Diarrhea (62%), nausea (24%), abdominal pain (15%), vomiting (12%), decreased appetite (11%)

Hepatic: Increased liver enzymes (14%)

1% to 10%:

Cardiovascular: Hypertension (5%), arterial thrombosis (3%), myocardial infarction (2%)

Central nervous system: Headache (8%)

Endocrine & metabolic: Weight loss (10%), hypothyroidism (1%)

Hematologic and oncologic: Hemorrhage (10%)

Respiratory: Bronchitis (1%)

<1% (Limited to important or life-threatening): Gastrointestinal perforation, major hemorrhage, pancreatitis, thrombocytopenia

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.

Data not available

Use is not recommended and a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. Excreted into human milk: Unknown Excreted into animal milk: Yes Comments: The effects in the nursing infant are unknown.