Symdeko (tezacaftor / ivacaftor)

What is Symdeko (tezacaftor/ivacaftor)?

Symdeko (tezacaftor/ivacaftor) is a medicine for the treatment of patients with cystic fibrosis (CF) aged 12 years and older. It is available in tablet form each containing 100 mg of tezacaftor and 150 mg of ivacaftor. It is indicated in combination with another medicine containing 150 mg ivacaftor alone^1,2. It is commercialized in Europe under the brand name Symkevi and in United States under the brand name Symdeko^1,2.

Who is Symdeko (tezacaftor/ivacaftor) for?

Symdeko (tezacaftor/ivacaftor) is for patients with cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation.

The F508del mutation can either be on both copies (homozygous) of CFTR gene; or one copy of F508del mutation (heterozygous) and another copy of following mutations in the CFTR gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272-26A→G, and 3849+10kbC→T^1,2. Symdeko (tezacaftor/ivacaftor) is only for patients who harbour one of the above mutations.

How does Symdeko (tezacaftor/ivacaftor) work?

Cystic Fibrosis (CF) is a serious genetic disorder characterised 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 diabetes³. 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 sticky⁴.

Symdeko (tezacaftor/ivacaftor) addresses this problem from two sides. One of the active substances, tezacaftor, 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 thick⁴.

Where has Symdeko (tezacaftor/ivacaftor) been approved?

Symdeko (tezacaftor/ivacaftor) was approved, in a combination regimen with ivacaftor for the treatment of patients with cystic fibrosis in presence of homozygous F508del mutation; or heterozygous F508del mutation plus another mutation in the CFTR gene, by^1,2:

• Health Canada, June 28, 2018, commercialised under the brand name Symdeko⁶
• European Medical Agency (EMA), European Union, October 31, 2018, commercialised under the brand name Symkevi¹
• Food and Drug Administration (FDA), USA, December 2, 2018, commercialised under the brand name Symdeko²
• Therapeutic Goods Administration (TGA), Australia, March 5, 2019, commercialised under the brand name Symdeko⁷.

Please note that this medicine may have also been approved in other regions than the ones we’ve listed. If you have a question about its approval in a specific country feel free to contact our support team.

How is Symdeko (tezacaftor/ivacaftor) taken?

The standard dosage is^1,2:

• A combination regimen with ivacaftor 150 mg tablets
• Taken orally twice a day
• One tablet every 12 hours with fat containing food
• Each tablet contains 100 mg of tezacaftor and 150 mg of ivacaftor.

Reduction in dose may be required in patients with moderate or severe hepatic impairment. When co-administered with strong CYP3A inhibitors, the dose should be adjusted to one Symdeko (tezacaftor/ivacaftor) tablet twice a week, taken approximately 3 to 4 days apart. In these cases, the evening dose of ivacaftor should not be taken^1,2. During treatment with Symdeko (tezacaftor/ivacaftor), interactions with strong CYP3A inhibitors and strong CYP3A4 inducers should be avoided^1,2.

Complete information about Symdeko (tezacaftor/ivacaftor) dosage and administration can be found in the official prescribing information listed in our references section^1,2.

Note: Please consult with your treating doctor for personalised dosing and potential drug interactions.

Are there any known side effects or adverse reactions of Symdeko (tezacaftor/ivacaftor)?

The most common adverse reactions listed in the prescribing information include^1,2:

• headache
• nasopharyngitis (upper respiratory infection)
• dizziness
• sinus congestion.

For a comprehensive list of side effects and adverse reactions please refer to the official prescribing information^1,2.

References

1. Summary of Product Characteristics [EMA]: Symkevi (tezacaftor/ivacaftor) [PDF]

Vertex Pharmaceuticals Limited, October 2018.

2. Summary of Product Characteristics [FDA]: Symdeko (tezacaftor/ivacaftor) [PDF]

Vertex Pharmaceuticals Incorporated, December 2018.

3. US National Library of Medicine, Genetics Home Reference: Cystic fibrosis

Published: 12/02/2019, cited on 13/02/2019.

4. EMA. Human Medicines: Symkevi (tezacaftor/ivacaftor)

27/07/2018, (last update: 27/07/2018), cited on 13/02/2019.

5. Naylor, M.G., et al. Recommendations for using standardised phenotypes in genetic association studies

Hum Genomics. 2009; 3 (4): 308–319

6. Summary of Product Characteristics [Health Canada]: Symdeko (tezacaftor/ivacaftor) [PDF]

Vertex Pharmaceuticals Incorporated, June 2018.

7. Summary of Product Characteristics [TGA]: Symdeko (tezacaftor/ivacaftor) [PDF]

Vertex Pharmaceuticals, March 2019.