Nintedanib

What is nintedanib used for?

Nintedanib is used to treat idiopathic pulmonary fibrosis. It is used to slow the progress of lung disease in some people.

Description

OFEV capsules contain nintedanib, a kinase inhibitor . Nintedanib is presented as the ethanesulfonate salt (esylate), with the chemical name 1H-Indole-6-carboxylic acid, 2,3-dihydro-3-[[[4-[methyl[(4-methyl-1-piperazinyl)acetyl]amino]phenyl]amino]phenylmethylene]-2-oxo-,methyl ester, (3Z)-, ethanesulfonate (1:1).

Its structural formula is:

Nintedanib esylate is a bright yellow powder with an empirical formula of C31H33N5O4∙C2H6O3S and a molecular weight of 649.76 g/mol.

OFEV capsules for oral administration are available in 2 dose strengths containing 100 mg or 150 mg of nintedanib (equivalent to 120.40 mg or 180.60 mg nintedanib ethanesulfonate, respectively). The inactive ingredients of OFEV are the following: Fill Material: triglycerides, hard fat, lecithin. Capsule Shell: gelatin, glycerol, titanium dioxide, red ferric oxide, yellow ferric oxide, black ink.

Mechanism of Action

Nintedanib is a small molecule that inhibits multiple receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (nRTKs). Nintedanib inhibits the following RTKs: platelet-derived growth factor receptor (PDGFR) α and β, fibroblast growth factor receptor (FGFR) 1-3, vascular endothelial growth factor receptor (VEGFR) 1-3, colony stimulating factor 1 receptor (CSF1R), and Fms-like tyrosine kinase-3 (FLT-3). These kinases except for FLT-3 have been implicated in pathogenesis of interstitial lung diseases (ILD).

Nintedanib binds competitively to the adenosine triphosphate (ATP) binding pocket of these kinases and blocks the intracellular signaling cascades, which have been demonstrated to be involved in the pathogenesis of fibrotic tissue remodeling in ILD. Nintedanib also inhibits the following nRTKs: Lck, Lyn and Src kinases. The contribution of FLT-3 and nRTK inhibition to nintedanib efficacy in ILD is unknown.

Before taking nintedanib, tell your doctor:

• If you are allergic to nintedanib; any part of this medicine; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had.
• 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 nintedanib.

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

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 nintedanib with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take nintedanib?

For all patients taking nintedanib:

• Tell all of your health care providers that you take nintedanib. This includes your doctors, nurses, pharmacists, and dentists.
• You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor. Rarely, some bleeding problems have been deadly.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• High blood pressure has happened with nintedanib. Have your blood pressure checked as you have been told by your doctor.
• This medicine may cause fertility problems. This may affect being able to have children. Talk with the doctor.
• Birth control pills and other hormone-based birth control may not work as well to prevent pregnancy. Use some other kind of birth control also like a condom when taking nintedanib.
• This medicine may cause harm to an unborn baby. A pregnancy test will be done before you start nintedanib to show that you are NOT pregnant.
• Women must use birth control while taking nintedanib and for some time after the last dose. Ask your doctor how long to use birth control. If you get pregnant, call your doctor right away.

If you smoke:

• Stop smoking before starting nintedanib. Avoid smoking while taking it. Smoking may lower how well nintedanib works. Talk with your doctor.

How is nintedanib best taken?

Use nintedanib as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take nintedanib with food.
• Swallow whole with some water or other drink.
• Do not chew or crush.
• Keep taking nintedanib as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

• Skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

What are the side effects of nintedanib that I need to call my doctor about immediately?

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, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of bleeding like throwing up or coughing up blood; vomit that looks like coffee grounds; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a cause or that get bigger; or bleeding you cannot stop.
• Signs of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
• Very bad and sometimes deadly liver problems have happened with nintedanib. Call your doctor right away if you have 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.
• This medicine may raise the chance of holes or tears in the stomach or bowels. Sometimes, this has been deadly. 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 nintedanib. 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.

What are some other side effects of nintedanib?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Stomach pain.
• Weight loss.
• Feeling dizzy, tired, or weak.
• Back pain.
• Diarrhea, throwing up, upset stomach, and feeling less hungry are common with nintedanib. If these happen, talk with your doctor about ways to lower these side effects. Call your doctor right away if any of these effects bother you, do not get better, or get very bad.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-332-1088. You may also report side effects at https://www.fda.gov/medwatch.

If overdose is suspected:

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

How do I store and/or throw out nintedanib?

• Store at room temperature.
• Protect from heat.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.

Label

PRINCIPAL DISPLAY PANEL – 150 MG CAPSULE BOTTLE CARTON

• NDC 0597-0145-60
• Ofev®
  (nintedanib
  capsules)
• 150 mg
• Rx only
• 60 capsules
• Boehringer
  Ingelheim

PRINCIPAL DISPLAY PANEL – 100 MG CAPSULE BOTTLE CARTON

• NDC 0597-0143-60
• Ofev®
  (nintedanib capsules)
• 100 mg
• Rx only
• 60 capsules
• Boehringer
  Ingelheim

SRC: NLM .