| Manufacturer || Vertex Pharmaceuticals
| Disease || Cystic Fibrosis
| Indication || Cystic fibrosis with F508del mutation
| Mode of Action || CFTR potentiator (targeted therapy)
| Approval Status || EMA approved (EU); FDA approved (USA); TGA approved (AUS)
| Strength || 200 mg / 125 mg
Who is lumacaftor / ivacaftor for?
Orkambi (lumacaftor / ivacaftor) is indicated for the treatment of cystic fibrosis (CF) in patients who are homozygous for the F508del mutation in the CFTR gene 
. The dosage 200 mg / 125 mg it is indicated for patients who are 12 years or older 
. The FDA only approved dosage of 100 mg/ 125 mg, is indicated for patients aged 6 to 11 years 
Complete information about Orkambi (lumacaftor / ivacaftor) dosage and administration can be found here: 
The standard dosage for patients aged 12 years or older is:
- two tablets (each containing 200 mg of lumacaftor and 125 mg of ivacaftor) taken orally every 12 hours 
The standard dosage for pediatric patients aged 6 to 11 years (FDA approved only):
- two tablets (each containing 100 mg of lumacaftor and 125 mg of ivacaftor) taken orally every 12 hours .
Reduce dose in patients with moderate or severe hepatic impairment. When initiating Orkambi (lumacaftor / ivacaftor) in patients taking strong CYP3A inhibitors, reduce Orkambi (lumacaftor / ivacaftor) dose for the first week of treatment 
.Consult your treating doctor for personalised dosing.
What is lumacaftor / ivacaftor and how does it work?
Orkambi (lumacaftor / ivacaftor), a combination of two active ingredients, lumacaftor and ivacaftor, is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, indicated for the treatment of cystic fibrosis (CF) in patients who are homozygous for the F508del mutation in the CFTR gene. This is the first medicine for cystic fibrosis directed at treating the cause of the disease in people who have this specific mutation 
CF is a serious genetic disorder characterized by the formation of thick mucus that accumulates in the lungs, digestive tract and other parts of the body leading to severe respiratory and digestive problems, as well as other complications such as infections and diabetes 
. Mutations in the CFTR gene are responsible for this disease. This gene makes a protein called ‘cystic-fibrosis transmembrane conductance regulator’ (CFTR), which is involved in regulating the production of mucus and digestive juices. These mutations reduce the number of CFTR protein channels on the cell surface, or affect the way they work. These channels are used for the transport of ions (charged atoms and molecules) in and out of cells. When the channels are defective, mucus and digestive juices can become abnormally thick and sticky 
. Orkambi addresses this problem from two sides. One of the active substance, lumacaftor, increases the number of CFTR proteins on the cell surface and the other, ivacaftor, increases the activity of the defective CFTR protein. This normalises the transport of ions through channels making the secretions less thick 
What is lumacaftor / ivacaftor's approval status?
Orkambi (lumacaftor / ivacaftor) was approved by:
- FDA (USA) on July 2, 2015 
- EMA (EU) on November 19, 2015 
- TGA (AUS) on March 3, 2016 
for the treatment of cystic fibrosis (CF) in patients who are homozygous for the F508del mutation in the CFTR gene.
The approvals were based on two double-blind, placebo-controlled clinical trials involving a total of 1,108 participants with CF who were 12 years and older with the F508del mutation. In both studies, participants with CF who took Orkambi (lumacaftor / ivacaftor), two pills every 12 hours, demonstrated improved lung function compared to those who took placebo 
. The most relevant measure for the evaluation of the study results after 24 weeks was the the percentage of predicted forced expiratory volume in one second (ppFEV), which is the amount of air a person can blow out in one second divided by the expected amount, calculated by taking into account several factors such as the person's sex and height 
. After 24 weeks of treatment, patients who took Orkambi (lumacaftor / ivacaftor) had an average improvement in ppFEV of 2.41 % more than those who took placebo in the first study, and 2.65 % in the second study. Treatment with Orkambi (lumacaftor / ivacaftor) also led to a reduction of 39 % in the number of exacerbations requiring hospital admission or antibiotic therapy 
The most common adverse reactions were dyspnea, nasopharyngitis, nausea, diarrhea, upper respiratory tract infection, fatigue, respiration abnormal, blood creatine phosphokinase increased, rash, flatulence, rhinorrhea, influenza 
Summary of Product Characteristics [FDA]: Orkambi (lumacaftor / ivacaftor), Vertex Pharmaceuticals Inc., Nov. 2016. http://pi.vrtx.com/files/uspi_lumacaftor_ivacaftor.pdf
Summary of Product Characteristics [EMA]: Orkambi (lumacaftor / ivacaftor), Vertex Pharmaceuticals Europe Ltd., Jan. 2017. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003954/WC500197611.pdf
Summary of Product Characteristics [TGA]: Orkambi (lumacaftor / ivacaftor), Vertex Pharmaceuticals (Australia) Pty Ltd, Mar. 2016. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2016-PI-01411-1&d=2017061916114622483
FDA News Release: FDA approves new treatment for cystic fibrosis, 02/07/2015. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm453565.htm
EMA. Human Medicines: Orkambi (lumacaftor / ivacaftor), 1/12/2015, (last update: 24/01/2017), cited on 20/06/2017. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/003954/human_med_001935.jsp&mid=WC0b01ac058001d124
Naylor, M.G., et al. Recommendations for using standardised phenotypes in genetic association studies. Hum Genomics. 2009; 3 (4): 308–319. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525193/