Immediate effects of lumacaftor/ivacaftor administration on lung function in patients with severe cystic fibrosis lung disease.
Safety-data for lumacaftor/ivacaftor (LUM/IVA) combination therapy in patients with severe lung disease (percent predicted forced expiratory volume in 1s [ppFEV1] <40) remain limited. We report immediate post-dose respiratory-related adverse events in 12 patients with severe cystic fibrosis (CF) lung disease (median [IQR] ppFEV1: 34 [31-36]) prescribed LUM/IVA. All patients experienced a decline in ppFEV1from baseline at 2-hours (median [IQR] relative change: -19 [-21 to -11]%, p<0.001) that persisted at 24-hours but recovered in most patients at 1-month. No pre- and post-differences in bronchodilator response were observed. Ten (83.3%) patients reported non-severe respiratory-related adverse events within 24-hours of LUM/IVA initiation. At 1-month, eight (67%) patients had persistent symptoms and six (50%) were treated for a pulmonary exacerbation. Our results highlight that LUM/IVA respiratory-related adverse events are common in patients with a ppFEV1<40. We recommend close assessment of adverse events. Further studies are required to evaluate the efficacy of LUM/IVA in patients with severe lung disease.
Pharmacy Department, Sir Charles Gairdner Hospital, Perth, Australia; Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, Australia; School of Medicine & Pharmacology, University of Western Australia, Perth, Australia. Electronic address: Natalia.popowicz@health.wa.gov.au.
Natalia
N
Popowicz
Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, Australia; Physiotherapy Department, Sir Charles Gairdner Hospital, Perth, Australia.
Jamie
J
Wood
Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, Australia.
Anna
A
Tai
Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, Australia.
Sue
S
Morey
Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, Australia; School of Medicine & Pharmacology, University of Western Australia, Perth, Australia.
Siobhain
S
Mulrennan
D000328:Adult; D000627:Aminophenols / Q000008:administration & dosage / Q000009:adverse effects; D000631:Aminopyridines / Q000008:administration & dosage / Q000009:adverse effects; D001315:Australia; D052117:Benzodioxoles / Q000008:administration & dosage / Q000009:adverse effects; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004338:Drug Combinations; D016903:Drug Monitoring / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000503:physiopathology; D004417:Dyspnea / Q000175:diagnosis / Q000209:etiology; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D049990:Membrane Transport Modulators / Q000008:administration & dosage / Q000009:adverse effects; D009154:Mutation; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects; D012129:Respiratory Function Tests / Q000379:methods; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000627:Aminophenols; D000631:Aminopyridines; D052117:Benzodioxoles; D004338:Drug Combinations; D049990:Membrane Transport Modulators; D015363:Quinolones; C000599212:lumacaftor, ivacaftor drug combination; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
Cystic fibrosis; Ivacaftor; Lumacaftor; Lung function, adverse events