A current review of the safety of cystic fibrosis transmembrane conductance regulator modulators

Abstract

What is known and objective Treatment with cystic fibrosis transmembrane conductance regulator (CFTR) modulators has led to improved clinical outcomes and an increase in lifespans of cystic fibrosis (CF) patients. As CF patients continue to live longer, they are at risk for developing adverse drug reactions associated with polypharmacy and CFTR modulators. Comment The authors aim to describe safety concerns of the current combination CFTR modulators, based upon a literature review, including notable safety concerns and recommendations for drug‐drug interactions. What is new and conclusion Cystic fibrosis transmembrane conductance regulator agents are generally well tolerated with low discontinuation rates when compared to placebo. Elevations in liver enzymes and drug‐drug interactions are the most notable safety concerns. Additionally, lumacaftor/ivacaftor has shown more respiratory‐related adverse events and drug‐drug interactions compared to elexacaftor/tezacaftor/ivacaftor and tezacaftor/ivacaftor. Postmarketing studies are needed to determine long‐term safety concerns.

Patient personalized translational tools in cystic fibrosis to transform data from bench to bed-side and back

“…The incidence of adverse events have been found to be similar in placebo and Ivacaftor groups (9). The most commonly reported adverse events occurring in Ivacaftor monotherapy are headache, upper respiratory tract infection, nasal congestion, diarrhea, rash, and dizziness (6,9,10). In general, Ivacaftor has been shown to have an acceptable safety profile both among children and older population during twice-daily administration for 48 wk.…”

“…Ivacaftor is categorized as a "CF potentiator" for its ability to increase the time that activated CFTR channels at the cell surface remain open (6,7). Lumacaftor, Tezacaftor, and Elexacaftor are different generations of "CF correctors" that are designed to help mutant CFTR fold efficiently to prevent ER-associated degradation of the mutant protein (8,9). In the clinical trials and the real world, Ivacaftor has shown improvement in FEV1 lung function, pulmonary exacerbations, the need of hospitalization and IV (intravenous) antibiotics in patients with CFTR gating mutation G551D in both age-adjusted pediatric and adult patients (6,9,10).…”

“…Lumacaftor, Tezacaftor, and Elexacaftor are different generations of "CF correctors" that are designed to help mutant CFTR fold efficiently to prevent ER-associated degradation of the mutant protein (8,9). In the clinical trials and the real world, Ivacaftor has shown improvement in FEV1 lung function, pulmonary exacerbations, the need of hospitalization and IV (intravenous) antibiotics in patients with CFTR gating mutation G551D in both age-adjusted pediatric and adult patients (6,9,10). The incidence of adverse events have been found to be similar in placebo and Ivacaftor groups (9).…”

“…In the clinical trials and the real world, Ivacaftor has shown improvement in FEV1 lung function, pulmonary exacerbations, the need of hospitalization and IV (intravenous) antibiotics in patients with CFTR gating mutation G551D in both age-adjusted pediatric and adult patients (6,9,10). The incidence of adverse events have been found to be similar in placebo and Ivacaftor groups (9). The most commonly reported adverse events occurring in Ivacaftor monotherapy are headache, upper respiratory tract infection, nasal congestion, diarrhea, rash, and dizziness (6,9,10).…”

Clinical Efficacy and Safety of Ivacaftor/Lumacaftor Combination in Patients with Cystic Fibrosis: International Studies Review

“…Побочные эффекты и взаимодействие ивакафтора/лумакафтора с другими лекарственными препаратами Таким образом, наиболее распространенные нежелательные явления, наблюдавшиеся в клинических исследованиях фазы II и III Ива/Лум, включали кашель (21-50%), бронхолегочное обострение (18-59%), заложенность носа (11-20,7%), боль в ротоглотке (6,5-20%), головную боль (4,8-20,7%) и одышку (13-43%) [32]. Во время испытаний фазы III < 4% пациентов как в группе Ива/Лум, так и в группе плацебо прекратили лечение из-за нежелательных явлений.…”