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Drugs for Cystic Fibrosis
Trikafta
elexacaftor/tezacaftor/ivacaftor
- transmembrane conductance regulator potentiator
- Approved for ages 2 and older
Cataracts with Lumacaftor/Ivacaftor
- Cataracts were found in juvenile rats in pre-clinical toxicology studies
- Cataracts have been discovered in a few children taking this drug. The concomitant use of steroids or other pre-existing coniditions could not be excluded.
- Drug manufacturer recommends baseline and follow-up eye examinations of unspecified interval or duration
Ocular Complications of Elexacaftor/Tezacaftor/Ivacaftor (Trikafta)
Cataracts / Lens Opacities
- Non-congenital lens opacities have been reported in pediatric patients on ivacaftor-containing regimens. Confounders (corticosteroid use, radiation exposure) were present in some cases, but a drug-attributable risk cannot be excluded.*[1]
- Signal originates from juvenile animal toxicology: cataracts occurred in rats dosed from postnatal day 7 through 35 at ivacaftor >=10 mg/kg/day (0.21x MRHD by systemic exposure); not seen in older animals.*[1]
- In clinical trials, cataracts are classified as an uncommon adverse event across all CFTR modulators, including ETI, and were not observed as a treatment effect in human trials.*[2][3]
Intracranial Hypertension
- Reported postmarketing; manifestations include headache, blurred vision, diplopia, and potential vision loss, with papilledema on fundoscopy.*[1]
- Patients with elevated vitamin A levels may be at increased risk — relevant given routine fat-soluble vitamin supplementation in CF.*[1]
- If unusual headache or visual disturbance occurs and IH is suspected, interrupt Trikafta and refer for prompt medical evaluation; monitor until resolution and for recurrence. Resumption requires individualized risk-benefit assessment.*[1]
Other Reported Ocular Symptoms
In a single-center survey after ETI initiation, ophthalmic complaints were the most frequently reported “other” side effect (7.6%), including cataracts (2.2%), blurred vision (2.2%), and epiphora (1.1%).[4]
Practical Monitoring Approach
| Element | Recommendation |
|---|---|
| Baseline eye exam | Recommended in pediatric patients before/at initiation of ETI |
| Follow-up exams | Follow-up ophthalmologic examinations recommended in pediatric patients; commonly operationalized as annual exams through age |
| Adults | No routine screening exam mandated by label; evaluate symptom-driven |
| New headache or visual disturbance (any age) | Interrupt drug; urgent evaluation including fundoscopy for papilledema; consider vitamin A level |
| Class effect | Same cataract monitoring applies to ivacaftor, lumacaftor-ivacaftor, and tezacaftor-ivacaftor |
The recommended exam should include slit-lamp assessment for lens opacities and fundoscopy. The label does not specify a fixed interval beyond “baseline and follow-up”; annual examination during childhood is the convention derived from review guidance.[3]
References
1. Trikafta. Food and Drug Administration. Updated date: 2026-06-22. 2. Cystic Fibrosis. Grasemann H, Ratjen F. The New England Journal of Medicine. 2023;389(18):1693-1707. doi:10.1056/NEJMra2216474. 3. Cystic Fibrosis. Ong T, Ramsey BW. JAMA. 2023;329(21):1859-1871. doi:10.1001/jama.2023.8120. 4. Heterogeneity in Reported Side Effects Following Initiation of Elexacaftor‐Tezacaftor‐Ivacaftor: Experiences at a Quaternary CF Care Center. Papadakis L, Stander T, Mombourquette J, et al. Pediatric Pulmonology. 2025;60(1):e27382. doi:10.1002/ppul.27382.