Nintedanib (Oral)

Nintedanib, marketed under the name of Ofev, is a drug used in the treatment of idiopathic pulmonary fibrosis, and while it can cause significant side effects, it is one of the only treatments currently available for this disease.

Overview

Nintedanib is a type of drug known as a tyrosine kinase inhibitor. The drug is used to treat a condition called idiopathic pulmonary fibrosis. This is a serious disease that progresses over the course of time. Nintedanib will not cure idiopathic pulmonary fibrosis. The purpose of the drug is to slow the progression of the disease.

To understand how the drug works, some knowledge of idiopathic pulmonary fibrosis is necessary. In the disease, the lungs become inflamed and develop scar tissue. This limits the ability of the lungs to work properly. The more scar tissue that develops, the harder it becomes for the patient to breathe. Some patients will have periods where the inflammation and scarring are not progressing as quickly as other times. Then, the patient will experience an acute exacerbation of inflammation.

Nintedanib works in two different ways to help patients with idiopathic pulmonary fibrosis. The drug helps to block the substances in the body that cause the scar tissue to develop. By doing this, the patient is then held in a steady state with the disease for a period of time.

In several different studies, nintedanib was shown to reduce the progression of idiopathic pulmonary fibrosis by 50 percent. In another study, 80 percent of patients were kept from having an acute exacerbation of the disease. Nintedanib also appears, at this point, to help patients to have a reduction in the number of times when they feel short of breath.

This drug has some serious side effects associated with it. Over 60 percent of those who are on the drug develop diarrhea. It can be severe enough to cause a modification in the dosage of the drug. There are several other significant side effects associated with taking nintedanib that include the gastrointestinal system, cardiovascular system and endocrine system.

Those who have existing liver problems may not be able to take nintedanib. One of the possible side effects of the drug is increased liver function blood tests and liver abnormalities. Those with existing liver problems may have an exacerbation of symptoms if the drug is used. During the course of the treatment with this medication, the doctor will perform regular blood tests to monitor liver functions. Normally, a liver function test will be performed before a patient is placed on the drug.

Several different medications react and cause interactions with nintedanib. It is important that patients inform their healthcare providers regarding all prescription, nonprescription and herbal supplements that they are taking prior to being placed on nintedanib.

Conditions Treated

  • Idiopathic Pulmonary Fibrosis

Type Of Medication

  • Tyrosine Kinase Inhibitor

Side Effects

There are several significant side effects associated with the use of this medication. The patient should bear in mind that this is one of the only medications that is proven to slow the progression of idiopathic pulmonary fibrosis. If possible, the prescribing physician will want the patient to remain on the medication.

The most often reported side effect associated with nintedanib is diarrhea. This has been noted in about 62 percent of the patients taking the drug. Sometimes, the diarrhea will become severe enough that the dosage of nintedanib must be modified in order to decrease the amount of diarrhea that the patient is experiencing.

Gastrointestinal symptoms are by in large the major side effect of the drug. In addition to diarrhea, almost one-fourth of patients experience nausea, and an additional 15 percent of patients experience abdominal pain and decreased appetite. Loss of weight is not uncommon while on the medication.

There is one serious gastrointestinal side effect that is potentially life threatening. In a very small number of patients, gastrointestinal perforation has occurred. If the patient is experiencing severe abdominal pain, the patient should seek medical attention immediately.

As noted, nintedanib can lead to elevation of liver enzymes. This occurs in approximately 14 percent of those on the drug. The doctor will monitor the blood regularly to check for abnormality in liver enzyme tests and reduced liver functions.

Some cardiovascular side effects have been noted with nintedanib. The most highly reported side effect in this area was hypertension. Usually, this was not severe enough to cause discontinuation of the drug. Also, about 2.5 percent of patients reported a blood clot while on the drug. On a more serious note, 1.5 percent of patients reported a myocardial infarction while taking nintedanib.

The other side effect that occurred in over one percent of those taking the drug was hypothyroidism. This occurred in 1.1 percent of patients.

The following side effects have been reported in small numbers:

  • Blood in the urine

Dosage

The normal dose of this drug is one 150 milligram capsule taken every 12 hours. This drug should always be taken with food.

If diarrhea, nausea or vomiting develops, the following should be observed:

  • Temporarily halt the treatment and make sure that the patient is sufficiently hydrated.

If liver function tests come back elevated, the following should be observed:

  • If the AST/ALT liver enzyme test is between 3 and 5, the drug should be halted until the enzymes return to normal.

Interactions

Nintedanib interacts with a number of different medications. Nintedanib should not be used with the following medications:

  • Carbamazepine
  • Dexamethasone
  • Doxorubicin
  • Erythromycin lactobionate
  • Fosphenytoin
  • Nefazodone
  • Phenobarbital
  • Phenytoin
  • Primidone
  • Rifampin
  • St john's wort
  • Tenofovir df
  • Tipranavir
  • Vinblastine

While nintedanib may be used with the following medications, the patient should be monitored for possible interactions:

  • Abiraterone
  • Afatinib
  • Amiodarone
  • Apixaban
  • Argatroban
  • Atorvastatin
  • Azithromycin
  • Bivalirudin
  • Carvedilol
  • Clarithromycin
  • Cobicistat
  • Crizotinib
  • Cyclosporine
  • Dabigatran
  • Daclatasvir
  • Dalteparin
  • Darunavir
  • Diltiazem
  • Dipyridamole
  • Dronedarone
  • Eliglustat
  • Enoxaparin
  • Erythromycin base
  • Erythromycin ethylsuccinate
  • Erythromycin stearate
  • Etravirine
  • Glecaprevir/pibrentasvir
  • Grapefruit
  • Heparin
  • Itraconazole
  • Ivacaftor
  • Ketoconazole
  • Lapatinib
  • Ledipasvir/sofosbuvir
  • Lomitapide
  • Lopinavir
  • Mefloquine
  • Nelfinavir
  • Nicardipine
  • Nifedipine
  • Nilotinib
  • Ombitasvir/paritaprevir/ritonavir
  • Paliperidone
  • Pantoprazole
  • Ponatinib
  • Posaconazole
  • Progesterone micronized
  • Propafenone
  • Propranolol
  • Quinidine
  • Quinine
  • Ranolazine
  • Reserpine
  • Ritonavir
  • Rivaroxaban
  • Saquinavir
  • Simeprevir
  • Sunitinib
  • Suvorexant
  • Tacrolimus
  • Tamoxifen
  • Telithromycin
  • Ticagrelor
  • Ulipristal
  • Vandetanib
  • Vemurafenib
  • Verapamil
  • Warfarin

There do not appear to be any food interactions with this medication.

Warnings

Liver enzyme tests must always be performed before nintedanib is started. The drug is known to impair liver functions. The doctor will monitor the patient during the course of the treatment with this drug. The drug may need to be discontinued if the patient develops elevated liver enzymes.

Caution should be exercised in using this medication in patients with a known history of cardiovascular disease. Patients receiving the drug have reported blood clots and heart rhythm irregularities.

Patients with a known bleeding risk and patients on blood thinners may not be able to use nintedanib. About 10 percent of those on the drug reported bleeding. Those with bleeding risk must use this medication with caution.

Those who are pregnant or who are planning to become pregnant should not use the drug. It is advised that women of childbearing years have a pregnancy test before starting on the medication. Those women of childbearing years who are on the medication should use birth control while on the drug and for a period of at least three months after the drug is discontinued.

Nursing mothers should not breastfeed while on nintedanib. The drug does pass into the breast milk. A nursing child can develop serious adverse reactions if nintedanib is ingested. Nursing mothers are advised to cease breastfeeding while using the drug, or they should not use the drug until after the breastfeeding period has ended.

There is a slight risk of gastrointestinal perforation with nintedanib. Any patient who has had recent abdominal surgery should use this drug with extreme caution. If the patient experiences severe abdominal pain, it should be reported to a doctor immediately.

Most patients who are over the age of 65 should be able to tolerate the medication. Those over the age of 75 may need to have a modified dose of the drug depending on their ability to tolerate its effects on their systems.

This drug has not been tested on patients with kidney function disorders. It should be used with caution.

The drug has not been tested on children. Doctors should use with caution.

People who smoke should stop smoking while on nintedanib. Studies demonstrated that smokers received less of the drug into their system thus decreasing the ability of the drug to work effectively. Those who are having trouble quitting smoking should consult with their healthcare provider for assistance.

Storage

This medication should be stored at room temperatures no greater than 77 degrees Fahrenheit. The drug should be protected from exposure to high temperatures.

Summary

Nintedanib is a newer drug that is used to slow the progression of the serious disease idiopathic pulmonary fibrosis. The medication aids the patient by blocking a substance in the body that leads to additional scarring of the lungs. The drug limits the number of acute exacerbations of the condition, and it helps the patient to have fewer episodes where the patient becomes short of breath.

This drug does have a number of significant side effects associated with it. However, it is one of the only means to slow the progression of idiopathic pulmonary fibrosis. Patients should be kept on the drug if at all possible.

The most common side effect associated with nintedanib is diarrhea occurring in over 60 percent of patients. If diarrhea, vomiting or nausea is a significant problem for the patient, the patient's dose should be modified to a lower dosage in an attempt to keep the patient on the drug.

This drug is known to cause significant birth defects. Those of childbearing years should not use this medication. Birth control should be used while on the medicine and for at least three months after the medication was stopped.

All patients should have liver enzyme tests before taking the drug. The doctor will perform periodic liver enzyme tests while the patient is on the medication.

Patients should be aware the gastrointestinal perforation is possible during the course of treatment. Severe abdominal pain should be reported to the doctor immediately.