Symdeko Side Effects: What to Expect and When to Call Your Doctor

Like all prescription medications, Symdeko (tezacaftor/ivacaftor) can cause side effects. Most patients tolerate Symdeko well — and its overall safety profile is considered favorable, especially compared to earlier CFTR modulators like Orkambi (lumacaftor/ivacaftor), which was more likely to cause respiratory side effects. Knowing what to expect and which symptoms require urgent medical attention can help you stay safe and on treatment.

Common Side Effects of Symdeko

In clinical trials involving more than 600 patients, the most commonly reported side effects of Symdeko (occurring in 3% or more of patients and more frequently than placebo) were:

Headache — the most commonly reported side effect; usually mild to moderate

Nausea — often manageable; taking Symdeko with fat-containing food may help reduce nausea

Sinus congestion (nasopharyngitis) — stuffy nose, sinus pressure, and related symptoms

Dizziness — can affect alertness; avoid driving or hazardous activities until you know how Symdeko affects you

These side effects are generally mild and often improve as your body adjusts to the medication. If any of these are bothersome or don't go away, contact your healthcare provider.

Serious Side Effects: Call Your Doctor Right Away

Symdeko can cause serious side effects in some patients. These require prompt medical attention:

1. Liver Problems (Elevated Transaminases)

Elevated liver enzymes (ALT and AST) have been reported in patients taking Symdeko. Your doctor will monitor your liver function with blood tests before you start Symdeko, every 3 months during the first year, and annually thereafter. Call your doctor right away if you experience:

Pain or discomfort in the upper right abdomen

Yellowing of the skin or whites of the eyes (jaundice)

Loss of appetite, dark urine, or unusual fatigue

2. Cataracts / Lens Opacities (Especially in Children)

Non-congenital lens opacities (cataracts) have been reported in pediatric and adolescent patients treated with Symdeko and with ivacaftor alone. The relationship between Symdeko and cataracts is not fully understood, but as a precaution, children and adolescents should have eye examinations before starting Symdeko and periodically during treatment. Contact your doctor if you or your child notice:

Blurred or cloudy vision

Increased sensitivity to light or glare

Difficulty seeing at night

3. Increased Brain Pressure (Intracranial Hypertension)

Intracranial hypertension (IH) — increased pressure around the brain — has been reported in post-marketing use of drugs containing the same ingredients as Symdeko. Symptoms of IH include severe headache, blurred vision, double vision, and potential vision loss. If you experience these symptoms, stop Symdeko and seek immediate medical evaluation.

4. Serious Allergic Reactions

Serious allergic reactions, including anaphylaxis, have been reported with Symdeko. Go to the emergency room or call 911 immediately if you experience:

Hives, rash, or itching

Difficulty breathing or swallowing

Swelling of the face, lips, tongue, or throat

5. Mental Health Changes

Serious mental health problems — including anxiety, depression, suicidal thoughts and behaviors, and sleep disturbances — have been reported in people taking Symdeko. If you or a family member notice new or worsening mental health symptoms while on Symdeko, contact your doctor right away. In a mental health emergency, call 988 (Suicide and Crisis Lifeline).

How Symdeko's Side Effects Compare to Other CFTR Modulators

Symdeko has a generally more favorable tolerability profile than Orkambi (lumacaftor/ivacaftor). Orkambi is associated with a higher risk of respiratory side effects — including chest tightness and shortness of breath — than Symdeko. Symdeko was developed in part to improve on Orkambi's tolerability, and clinical trials confirmed this advantage.

Compared to Trikafta (elexacaftor/tezacaftor/ivacaftor), both drugs share similar tolerability profiles since they contain overlapping active ingredients. Some patients who experience specific side effects on Trikafta may tolerate Symdeko better — this is a clinical discussion to have with your CF specialist.

Tips for Managing Common Symdeko Side Effects

Headache: Over-the-counter pain relievers (check with your doctor) may help. Staying hydrated is also important.

Nausea: Always take Symdeko with a fat-containing food (like peanut butter, eggs, or avocado) to improve absorption and reduce nausea.

Dizziness: Avoid driving or operating machinery until you know how Symdeko affects you. Report persistent dizziness to your doctor.

Sinus symptoms: Saline nasal rinses and OTC decongestants may help — ask your CF team before using any new OTC products.

For more information, see our full guide: Symdeko Drug Interactions: What to Avoid and What to Tell Your Doctor.

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