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What Is Orkambi (Lumacaftor/Ivacaftor)?

Cystic fibrosis (CF) is a genetically inherited disease that affects a protein in the body. People with CF inherit two copies of a defective or mutated CF gene, meaning both parents carried the mutated gene for CF and passed it to their child. Called the cystic fibrosis transmembrane conductance regulator (CFTR) gene, this mutation affects production of the CFTR protein.

What is the CFTR protein?

A properly made CFTR protein helps cells move chloride, an element in salt, to the cell surface. In CF, the body creates a “broken” CFTR protein that can’t move chloride properly. Without chloride, water isn’t attracted to the cell surface, resulting in a thick, sticky mucus building up in the lungs and other organs. This mucus causes persistent lung infections, gastrointestinal issues, and gradually damages other organs. It affects the lungs the most, but also the digestive system, including the pancreas, liver, intestines, and kidneys. CF may also impact the ears, nose and sinuses, sex organs, and the bones and joints.

A class of drugs called CFTR modulators target specific defects in the CFTR protein so that it can work properly. One such drug is lumacaftor/ivacaftor, which goes by the brand name Orkambi.

What types of CF can Orkambi treat?

Lumacaftor/ivacaftor (Orkambi) is prescribed for people with CF who have two copies of the F508del mutation, which is the most common CF mutation. Approximately 48% of people with CF have two copies of the F508del mutation. It is prescribed to those age 2 and older.1

How does Orkambi work?

The CFTR modulator lumacaftor/ivacaftor is a combination of two drugs that work in two ways to help the CFTR protein move chloride across a cell surface. Lumacaftor is what is known as a corrector. This means that lumacaftor helps the CFTR protein form the correct shape so that it can move to the cell surface. Once there, about a third of the CFTR protein gets to the cell surface, which is still not enough to move chloride through the surface. That is why another CFTR modulator, ivacaftor is added. Ivacaftor is called a potentiator because it works differently than a corrector. Ivacaftor holds the “gate” on the cell surface open long enough for the chloride to pass through.

Combined, these two modulators reduce the symptoms of CF by rehydrating the thick, sticky mucus which makes it thinner. Lumacaftor/ivacaftor works only for a long as it is in the system, or about 12 hours. That is why the medication is prescribed to be taken every 12 hours. Lumacaftor/ivacaftor does not completely restore proper chloride flow in the cells or reverse lung damage, but it does relieve the symptoms of CF.1,3

How is Orkambi taken?

In children ages 2 to 5, the amount of lumacaftor/ivacaftor (Orkambi) taken is based on their weight. For young children, the drug comes in a packet that is mixed with soft food or a liquid that contains fat. Fatty foods commonly mixed with this drug include whole milk, eggs, avocado or peanut butter. For ages 6 and older, lumacaftor/ivacaftor is taken in two tablets every 12 hours, also with foods that contain fat.

What are the risks or common side effects with Orkambi?

The most common side effects of taking lumacaftor/ivacaftor (Orkambi) are:

  • Shortness of breath and tightness in the chest
  • Upper respiratory tract infections such as colds, sore throat, nasal and sinus congestion or runny nose
  • Nausea
  • Diarrhea and gas
  • Rash
  • Fatigue
  • Flu or flu-like symptoms
  • Higher muscle enzyme levels
  • Irregular, missed or abnormal menstrual periods in females1,2

Why is genetic testing important in cystic fibrosis?

CFTR modulators are designed to correct the specific type of malfunction that certain CF mutations cause. If you do not have one of these mutations, lumacaftor/ivacaftor will not work to correct why your CFTR protein fails to carry chloride through cells. This is why it is important to know which genetic mutation for CF you have. If you do not know your mutation, the CF Foundation offers free genetic testing for people with cystic fibrosis.

Written by: Jessica Johns Pool | Last reviewed: September 2019
  1. Cystic Fibrosis Foundation. CFTR Modulator Therapies. Available at: https://www.cff.org/Life-With-CF/Treatments-and-Therapies/Medications/CFTR-Modulator-Therapies. Accessed 5/29/2019.
  2. U.S. National Library of Medicine Daily Med. Orkambi-lumacaftor and ivacaftor tablet, film coated. Orkambi-lumacaftor and ivacaftor granule. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3fc1c40e-cfac-47a1-9e1a-61ead3570600. Accessed 5/29/2019.
  3. Cystic Fibrosis Foundation. CFTR Modulator Types. Available at: https://www.cff.org/Research/Developing-New-Treatments/CFTR-Modulator-Types. Accessed 5/29/2019.