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Content Update

Jan. 3, 2020

Elexacaftor/Tezacaftor/Ivacaftor (Trikafta): A New Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulator : In October 2019, the FDA approved the first triple combination CFTR modulator for patients ≥12 years of age with cystic fibrosis (CF) and at least one Phe508del allele, impacting nearly 90% of patients with CF. Clinical trials demonstrated significant improvement in lung function, sweat chloride concentrations, CF questionnaire-revised quality of life scores, body mass index, and a decrease in pulmonary exacerbations. Overall, elexacaftor/tezacaftor/ivacaftor offers a significant advance in the chronic management of CF.

LEARNING OBJECTIVES

LEARNING OBJECTIVES

Upon completion of the chapter, the reader will be able to:

  1. Explain the pathophysiology of cystic fibrosis (CF) and its multiorgan system involvement.

  2. Describe the common clinical presentation and diagnosis of CF.

  3. Consider long-term treatment goals with respect to clinical course and prognosis of CF.

  4. Identify nonpharmacologic therapies for CF management.

  5. Recommend appropriate pharmacologic therapies for chronic CF management.

  6. Design appropriate antibiotic regimens for acute pulmonary exacerbations of CF.

  7. Apply pharmacokinetic principles when calculating drug doses in CF patients.

  8. Formulate monitoring plans for acute and chronic CF pharmacotherapy.

INTRODUCTION

Cystic fibrosis (CF) is an inherited multiorgan system disorder affecting children and, increasingly, adults. It is the most common life-shortening genetic disease among whites and the major cause of severe chronic lung disease and pancreatic insufficiency in children. Disease generally manifests as mucosal obstruction of exocrine glands caused by defective ion transport within epithelial cells. Due to the array of affected organ systems and complicated medical therapies, appropriate CF treatment necessitates interprofessional team collaboration.

EPIDEMIOLOGY AND ETIOLOGY

In the United States, CF most commonly occurs in whites, affecting approximately 1 in 3200 individuals. CF is less common in Hispanics (1 in 9200 to 13,500), African Americans (1 in 15,000), and Asian Americans (1 in 35,000).1 CF is inherited as an autosomal recessive trait, and approximately 1 in 25 whites are heterozygous carriers. Offspring of a carrier couple (each parent being heterozygous) have a 1 in 4 chance of having the disease (homozygous), a 1 in 2 chance of being a carrier (heterozygous), and a 1 in 4 chance of receiving no trait. The CFTR gene mutation is found on the long arm of chromosome 7 and encodes for the CF transmembrane regulator (CFTR) protein, which functions as a chloride channel to transport water and electrolytes. Over 2000 mutations have been described in the CFTR gene; however, the Phe508del mutation (also known as F508del or ΔF508) is most common and is present in approximately 70% to 90% of CF patients.1-5

PATHOPHYSIOLOGY

CF is a disease of exocrine gland epithelial cells where CFTR expression is prevalent. Normally, these cells transport chloride through CFTR chloride channels with ...

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