Differences

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--- drugs_cystic_fibrosis [2026/08/03 10:23] – created Scott Larson
+++ drugs_cystic_fibrosis [2026/08/03 11:13] (current) – [References] Scott Larson
@@ Line 1: / Line 1: @@
 ====== Drugs for Cystic Fibrosis ======
+  * **Trikafta** (elexacaftor/tezacaftor/ivacaftor),
-<wrap>lumacaftor, ivacaftor</wrap>
+  * **Kalydeco** (ivacaftor)
+  * **Orkambi** (lumacaftor/ivacaftor)
-  * Drug used in the treatment of Cystic Fibrosis
+  * **Symdeko** (tezacaftor/ivacaftor)
-  * transmembrane conductance regulator potentiator
+  * **Alyftrek** (vanzacaftor/tezacaftor/deutivacaftor)
-  * Approved for ages 2 and older
+  * Outside North America, Trikafta is marketed as Kaftrio, and Symdeko as Symkevi
-  * [[https://www-bmj-com.proxy.lib.uiowa.edu/content/361/bmj.k1783|Review Article]]
+  * this class of drugs regular transmembrane conductance
-==== Cataracts with Lumacaftor/Ivacaftor ====
+==== Cataracts with Lumacaftor/Ivacaftor (Orkambi) ====
   * 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.
@@ Line 16: / Line 16: @@
     * [[https://pi.vrtx.com/files/uspi_lumacaftor_ivacaftor.pdf|Prescribing Information]]
-{{tag>drugs}}
+==== Ocular Complications of Elexacaftor/Tezacaftor/Ivacaftor (Trikafta) ====
-  * Drug used in the treatment of Cystic Fibrosis
+=== Cataracts / Lens Opacities ===
-  * transmembrane conductance regulator potentiator
-  * Approved for ages 2 and older
-  * [[https://www-bmj-com.proxy.lib.uiowa.edu/content/361/bmj.k1783|Review Article]]
-==== Cataracts with Lumacaftor/Ivacaftor ====
+  * 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]
-  * Cataracts were found in juvenile rats in pre-clinical toxicology studies
+  * 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]
-  * 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.
+  * 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]
-    * [[https://www.atsjournals.org/doi/10.1164/rccm.201608-1754OC#_i11|Lumacaftor/Ivacaftor in Patients Aged 6–11 Years with Cystic Fibrosis and Homozygous for F508del-CFTR]]
-    * [[https://adc-bmj-com.proxy.lib.uiowa.edu/content/103/1/68|The impact of 12 months treatment with ivacaftor on Scottish paediatric patients with cystic fibrosis with the G551D mutation: a review]]
+=== Intracranial Hypertension ===
-  * Drug manufacturer recommends baseline and follow-up eye examinations of unspecified interval or duration
-    * [[https://pi.vrtx.com/files/uspi_lumacaftor_ivacaftor.pdf|Prescribing Information]]
+  * 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 ====
+<WRAP round box 85%>
+^ 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; yearly exams most common|
+| 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]
+</WRAP>
+=====References=====
+  - [[https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212273s004lbl.pdf|Trikafta. Food and Drug Administration. Updated date: 2026-06-22]]
+  - [[https://www.nejm.org/doi/10.1056/NEJMra2216474|Cystic Fibrosis. Grasemann H, Ratjen F. The New England Journal of Medicine. 2023;389(18):1693-1707]]
+  - [[https://pubmed.ncbi.nlm.nih.gov/37278811/|Cystic Fibrosis. Ong T, Ramsey BW. JAMA. 2023;329(21):1859-1871]]
+  - [[https://pubmed.ncbi.nlm.nih.gov/39503182/|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]]
+  - [[https://pmc.ncbi.nlm.nih.gov/articles/PMC2137053/|Cystic Fibrosis. Davies JC et al. BMJ 2007;335(7632):1255–1259]]
 {{tag>drugs}}

drugs