Symdeko (tezacaftor / ivacaftor)
Also marketed as Symkevi. An approved treatment for Cystic Fibrosis.
The same compound appears under different names depending on the context. Here is how to identify Tezacaftor / Ivacaftor wherever you encounter it, plus the key facts at a glance.
- Generic name
- Tezacaftor / Ivacaftor
- Brand names
- Symdeko, Symkevi
- Development code
- VX-661/VX-770
- Drug class
- CFTR modulator combination
- Manufacturer
- Vertex Pharmaceuticals
- How it's taken
- Symdeko tablets are taken twice daily with a meal containing fat.
A second-generation dual CFTR modulator with a better side-effect profile than Orkambi. Approved for patients age 6 and older who have 2 copies of F508del or at least 1 responsive mutation, such as certain residual function mutations.
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Where Tezacaftor / Ivacaftor fits
Intermediate-generation CFTR modulator, positioned between lumacaftor-ivacaftor and Trikafta. Largely superseded by Trikafta for most eligible patients but still available for specific mutation profiles.
How Tezacaftor / Ivacaftor works
Symdeko combines a newer corrector (tezacaftor) with ivacaftor. Tezacaftor helps the CFTR protein fold correctly and move to the cell surface more effectively than earlier correctors. Once there, ivacaftor opens the chloride channel. This combination treats more CF mutations than previous therapies.
Mechanism: CFTR corrector + potentiator with fewer drug interactions than Orkambi
Side effects and safety
The most common side effects are headache, nausea, sinus congestion, and dizziness. The label warns about raised liver enzymes (blood tests before starting, every 3 months in the first year, then yearly), serious allergic reactions including anaphylaxis, increased pressure inside the skull (call your doctor about an unusual headache or vision changes), mood and mental health changes including depression, anxiety, sleep problems, and suicidal thoughts, and cataracts in children (eye exams before and during treatment). Avoid grapefruit. It should not be taken with strong CYP3A inducers such as rifampin or St. John's wort, because they can make it much less effective. Watch for yellowing of skin or eyes, dark urine, or unusual tiredness.
This is not a complete list of side effects. Talk to your doctor or pharmacist about what to expect and when to seek medical attention.
Taking Tezacaftor / Ivacaftor
Symdeko tablets are taken twice daily with a meal containing fat. For children ages 6-11, different dosing is used. It is approved only for people who have 2 copies of F508del or at least 1 mutation on the label's list of responsive mutations. People with 1 F508del and 1 minimal function mutation are not covered by the label, because a trial in that group did not show benefit.
Availability and cost
Only available as the brand-name product.
Second-generation CFTR corrector-potentiator combination with improved tolerability over lumacaftor-ivacaftor. Rare disease specialty pricing.
Help paying for Symdeko
Pick your insurance to see which help fits. Drugmaker copay cards can't be used with Medicare, Medicaid or TRICARE; charity funds are the usual route there.
- Copay help
Eligible patients with commercial insurance may pay as little as $0 per fill. Annual assistance up to $20,000. Not available with Medicare, Medicaid or TRICARE.
For: private insurance · source - Insurance and case manager help
Vertex GPS Support Specialists give one-on-one help with insurance coverage and financial assistance options while you are on treatment.
The official page does not say who qualifies. Ask the program. · source
Good to know: The copay terms come from the Vertex GPS financial assistance page, which applies to all prescribed Vertex CF medicines.
- From a charity · The Assistance FundCystic Fibrosis fundWaitlist
Pays for: Copays, coinsurance, deductibles and other health-related expenses.
The foundation says: “WAITLIST — Accepting Waitlist Patients. TAF is currently accepting requests to join the enrollment waitlist for this program. Waitlists a…”
Access and eligibility
Symdeko is approved for patients age 6 and older who have either two copies of the F508del mutation or at least one of several other specified responsive mutations.
Source: Symdeko.com (Vertex Pharmaceuticals)
Access program details are provided for informational purposes and may vary based on insurance coverage, geographic location, and individual circumstances. Confirm current eligibility directly with the manufacturer or your specialty pharmacy.
Clinical trial results
FDA approved Symdeko in February 2018 based on Phase 3 trials EVOLVE and EXPAND with 750 CF patients. In EVOLVE (2 copies of F508del), lung function (ppFEV1) improved by 4 percentage points more than placebo and the rate of pulmonary exacerbations (lung flare-ups) was 35% lower. In EXPAND (1 F508del plus a responsive mutation), ppFEV1 improved by 6.8 percentage points versus placebo.
Development history
Vertex Pharmaceuticals developed Symdeko as an improvement to Orkambi. Approved in February 2018, it expanded treatment to people with different mutation combinations than Orkambi could treat.
Explore Cystic Fibrosis trials
Other Cystic Fibrosis treatments
Common questions about Tezacaftor / Ivacaftor
▸What is Tezacaftor / Ivacaftor (Symdeko)?
A second-generation dual CFTR modulator with a better side-effect profile than Orkambi. Approved for patients age 6 and older who have 2 copies of F508del or at least 1 responsive mutation, such as certain residual function mutations.
▸How does Tezacaftor / Ivacaftor work?
Symdeko combines a newer corrector (tezacaftor) with ivacaftor. Tezacaftor helps the CFTR protein fold correctly and move to the cell surface more effectively than earlier correctors. Once there, ivacaftor opens the chloride channel. This combination treats more CF mutations than previous therapies.
▸What are the side effects of Tezacaftor / Ivacaftor?
The most common side effects are headache, nausea, sinus congestion, and dizziness. The label warns about raised liver enzymes (blood tests before starting, every 3 months in the first year, then yearly), serious allergic reactions including anaphylaxis, increased pressure inside the skull (call your doctor about an unusual headache or vision changes), mood and mental health changes including depression, anxiety, sleep problems, and suicidal thoughts, and cataracts in children (eye exams before and during treatment). Avoid grapefruit. It should not be taken with strong CYP3A inducers such as rifampin or St. John's wort, because they can make it much less effective. Watch for yellowing of skin or eyes, dark urine, or unusual tiredness.
▸How is Tezacaftor / Ivacaftor taken?
Symdeko tablets are taken twice daily with a meal containing fat. For children ages 6-11, different dosing is used. It is approved only for people who have 2 copies of F508del or at least 1 mutation on the label's list of responsive mutations. People with 1 F508del and 1 minimal function mutation are not covered by the label, because a trial in that group did not show benefit.
▸Is Tezacaftor / Ivacaftor FDA approved?
Yes, Tezacaftor / Ivacaftor (Symdeko) is FDA approved (2018) for the treatment of Cystic Fibrosis.
▸How does Symdeko compare to Orkambi?
Symdeko improved on Orkambi in several ways. The corrector component (tezacaftor) has fewer drug interactions than lumacaftor, making it easier to combine with other CF medications including hormonal contraceptives. No trial has compared Symdeko with Orkambi head to head. In its own trial in people with 2 copies of F508del, Symdeko improved lung function by 4.0 percentage points more than placebo. Symdeko also expanded eligibility to patients with certain residual function mutations beyond just homozygous F508del.
▸Why would a patient use Symdeko instead of Trikafta?
Most eligible patients have moved to Trikafta or Alyftrek, which show greater efficacy. However, Symdeko may still be used by patients who have been stable on it and prefer not to switch, those who cannot tolerate one of the three components in Trikafta, or patients with specific mutations where Symdeko is approved but Trikafta is not. Formulary and insurance considerations can also play a role in some cases.
▸What mutations does Symdeko cover?
Symdeko is approved for patients age 6 and older with either two copies of the F508del mutation (homozygous) or at least one of several specified responsive mutations, including some residual function mutations. This expanded the treatable population beyond what Orkambi could cover. Your CF genetic test results and the FDA-approved mutation list determine eligibility.
▸Does Symdeko require the same first-dose monitoring as other CF drugs?
No special first-dose monitoring is required for Symdeko, unlike fingolimod in MS. However, liver function tests should be checked before starting and periodically during treatment, as elevations in liver enzymes can occur. Standard CF clinic monitoring applies, including regular pulmonary function tests and sputum cultures.
▸What is the dosing schedule for Symdeko?
Symdeko is taken as one combination tablet (tezacaftor 100 mg / ivacaftor 150 mg) in the morning with fat-containing food, followed by one ivacaftor 150 mg tablet in the evening, approximately 12 hours later, also with fat-containing food. This twice-daily dosing is the same schedule as Trikafta. For children ages 6-11, weight-based dosing with different tablet strengths is used.