NAPLEX Question of the Week: Clear the Airway

Cystic fibrosis is the subject of our question of the week!
NAPLEX Question of the Week: Clear the Airway
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JT is a 6-year-old male who presents to your pharmacotherapy clinic for follow-up of his cystic fibrosis. The patient complains of worsening respiratory symptoms including cough with sputum. The second-year medical resident has a few questions regarding some of the medications on the patient’s chart and consults the pharmacist in the clinic. 

Which of the following statements are correct regarding the medications used in the management of cystic fibrosis? Select all that apply. 

 A. Orkambi is indicated in patients aged 2 years and older who are homozygous for the F508del mutation 

 B. Elevated transaminases (ALT/AST) have been observed in patients being treated with cystic fibrosis transmembrane conductance regulator (CFTR) modulators 

 C. Trikafta is indicated in patients aged 6 years and older who have at least one F508del mutation in the CFTR gene 

 D. Kalydeco is indicated in patients aged 2 years and older who are homozygous for the F508del mutation  

 E. Cataracts have been reported in pediatric patients being treated with cystic fibrosis transmembrane conductance regulator (CFTR) modulators 

 F. Symdeko is indicated in patients aged 2 years and older who are homozygous for the F508del mutation  

 

 

Answers with rationale:

Brand/Generics covered: Orkambi (lumacaftor/ivacaftor), Kalydeco (ivacaftor), Trikafta (elexacaftor/tezacaftor/ivacaftor), and Symdeko (tezacaftor/ivacaftor) 

The correct answers are A, B, C, E.  

Cystic fibrosis (CF) is a genetic disorder characterized by the buildup of thick mucus that affects multiple organs, including the lungs, pancreas, and digestive system. CF is caused by a mutation in the gene for the protein cystic fibrosis transmembrane conductance regulator (CFTR), with the most common CF mutation being F508del. While there is no cure, there are several medications used to manage cystic fibrosis including airway clearance therapies, enzymes and nutrients, antibiotics, anti-inflammatories, and cystic fibrosis transmembrane conductance regulator (CFTR) modulators. CFTR modulators (Kalydeco, Orkambi, Symdeko, and Trikafta) are disease-modifying therapies that target specific defects in the CFTR protein. These therapies are approved for specific mutations and ages so it’s important to know the age cut-offs and the mutations each modulator targets. 

Answer choice A is correct. Orkambi (lumacaftor/ivacaftor) is indicated for the treatment of CF in patients aged 2 years and older who are homozygous for the F508del mutation in the CFTR gene.  

Answer choice B is correct. Elevated transaminases have been reported in patients receiving CFTR modulators. It is recommended that ALT, AST, and bilirubin be assessed prior to initiating CFTR modulators, every 3 months during the first year of treatment, and annually thereafter.  

Answer choice C is correct. Trikafta (elexacaftor/tezacaftor/ivacaftor) is a triple-combination CFTR modulator indicated in patients aged 6 years and older who have at least one F508del mutation in the CFTR gene or a mutation in the CFTR gene that is responsive based on in vitro data.  

Answer choice D is incorrect. Kalydeco (ivacaftor) was the first CFTR modulator approved in 2012. Kalydeco is indicated in multiple genetic subtypes. See a complete list of approved mutations here. However, it is not effective in patients with CF who are homozygous for the F508del mutation in the CFTR gene. Therefore, answer choice D is incorrect.  

Answer choice E is correct. Non- congenital lens opacities/cataracts have been reported in pediatric patients treated with CFTR modulators. Baseline and follow-up ophthalmological exams are recommended in pediatric patients initiating CFTR modulator treatment. 

Answer choice F is incorrect. Symdeko (tezacaftor/ivacaftor) is indicated in patients aged 6 years and older who are homozygous for the F508del mutation or who have at least one mutation in the CFTR gene that is responsive based on in vitro data.  

NAPLEX Exam Competencies Covered: Area 2 (Identify Drug Characteristics), 2.1 Pharmacology, mechanism of action, or therapeutic class; 2.2 Commercial availability; prescription or non-prescription status; brand, generic, or biosimilar names; physical descriptions; or how supplied; Area 3 (Develop or Manage Treatment Plans), 3.7 Adverse drug effects, toxicology, or overdose, 6.4 Vulnerable populations, special populations, or risk prevention programs

References: 

Orkambi Package Insert 

Kalydeco Package Insert 

Trikafta Package Insert 

Symdeko Package Insert 

 See everyone next week!

Dr. B

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