Inhalation Tobramycin for the Management of Cystic Fibrosis

PICHON RIVIERE, A.; AUGUSTOVSKI, F.; GARCIA MARTI, S.; GLUJOVSKY, D.; LOPEZ, A.; REY-ARES, L.; ALCARAZ, A.; BARDACH, A.; CIAPPONI, A; SPIRA, C

Documento de Evaluación de Tecnologías Sanitarias

IECS

Año: 2013 p. 1 - 30

1668-2793

Cystic fibrosis (CF) is an autosomal recessive genetic disease caused by a mutation in the CFTR gene (Cystic Fibrosis Transmembrane Conductance Regulator) affecting 80,000 individuals worldwide. This genetic disorder results in dysfunction of the exocrine glands causing an intense inflammatory response of the airways, abnormal mucous, airway obstruction and tissue damage favoring pathogen bacteria growth. Pseudomona Aeruginosa (Pa) is one of the main colonization pathogens since this bacterium is the main cause of morbidity and mortality of this disease. Eradication of this microorganism colonization is essential to improve prognosis. Technology Tobramycin is a broad spectrum aminoglycoside antibiotic used for the treatment of PA chronic lung infection in patients with CF. Inhaled tobramycin has proven to be an alternative and effective route of administration. Purpose To assess the available evidence on the efficacy, safety and comparative coverage related aspects among different inhalation tobramycin formulations in patients with cystic fibrosis. Methods A bibliographic search was carried out on the main databases: DARE, NHS EED, on Internet general search engines, in health technology evaluation agencies and health sponsors. Priority was given to the inclusion of systematic reviews; controlled, randomized clinical trials (RCTs); health technology assessments and economic evaluations; clinical practice guidelines and coverage policies of other health systems. Additionally, the documents issued by the Argentine National Administration of Drugs, Food and Medical Technology (ANMAT) were reviewed as well as the Sciences and Technologies for your Pharmacy Magazine (Revista de Ciencias y Tecnologías para su farmacia) Kairos and AlphaBeta.net. Results One multicenter RCT, one coverage policy and five clinical practice guidelines were selected. In our setting, two types of inhalation tobramycin are available: Tobramycin inhalation solution (TIS) marketed as twelve products that do not differ in its administration or excipients but they differ in costs and Tobramycin inhalation powder (TIP) marketed as only one product. No studies comparing both types of solutions are found. The multicenter RCT published in 2011, compared the safety, efficacy and convenience of two different inhaled tobramycin formulations, TIS and TIP, in 517 patients, children over 6 years old and adults, with CF and forced expiratory volume in one second (FEV1) of 25% to 75% of predicted value and culture of sputum and throat positive for PA: TIS or TIP. The follow up period was 24 weeks where the patients completed three cycles of therapy; a 28 days on-treatment followed by 28 days off-treatment. No significant differences were found in the clinically relevant results such as incidence of serious adverse events, hematological determinations, hearing loss, increased FEV1 predicted in relation to baseline at day 28 of the third cycle; decrease in the Pa sputum density, increase in the tobramycin minimum inhibitory concentration against Pa; drug serum concentration and hospitalizations due to respiratory related events. TIP was associated to higher satisfaction (76.2 vs. 71.0; p=0.0018; 0 to 100 score scale), and shorter administration time (5.6 minutes vs. 19.7 minutes; p