Long-term safety and efficacy of tobramycin in the&amp;nbsp;management of cystic fibrosis

Vázquez-Espinosa, Emma; Girón, Rosa; Gómez-Punter, Rosa Mar; Castillo, Elena García; Valenzuela, Claudia; Cisneros, Carolina; Zamora, Enrique; García-Pérez, Francisco J.; Ancochea, Julio

doi:10.2147/tcrm.s75208

Cited by 18 publications

(11 citation statements)

References 46 publications

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“…Significance —Uncertain, therefore the effect of sputum antagonism requires further in-vivo investigation. Current data from CF patients support use of inhaled aminoglycosides [ 79 , 80 ].…”

Section: Factors Affecting Aerosolized Drug Delivery In the Criticallmentioning

confidence: 99%

Fundamentals of aerosol therapy in critical care

et al. 2016

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Drug dosing in critically ill patients is challenging due to the altered drug pharmacokinetics–pharmacodynamics associated with systemic therapies. For many drug therapies, there is potential to use the respiratory system as an alternative route for drug delivery. Aerosol drug delivery can provide many advantages over conventional therapy. Given that respiratory diseases are the commonest causes of critical illness, use of aerosol therapy to provide high local drug concentrations with minimal systemic side effects makes this route an attractive option. To date, limited evidence has restricted its wider application. The efficacy of aerosol drug therapy depends on drug-related factors (particle size, molecular weight), device factors, patient-related factors (airway anatomy, inhalation patterns) and mechanical ventilation-related factors (humidification, airway). This review identifies the relevant factors which require attention for optimization of aerosol drug delivery that can achieve better drug concentrations at the target sites and potentially improve clinical outcomes.

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Section: Factors Affecting Aerosolized Drug Delivery In the Criticallmentioning

confidence: 99%

Fundamentals of aerosol therapy in critical care

et al. 2016

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“…Although long‐term, intermittent TIS nebulization is considered to be safe and well tolerated, raised urinary NAG/creatinine ratios with the absence of decreased eGFR in the present study suggest TIS‐induced subclinical tubular kidney injury. Therefore, this study stresses the need for carefully monitoring for toxic effects of aminoglycosides in patients on chronic TIS therapy, especially when new nebulizers are used.…”

Section: Resultsmentioning

confidence: 99%

Pharmacokinetics and safety of tobramycin nebulization with the I‐neb and PARI‐LC Plus in children with cystic fibrosis: A randomized, crossover study

Velzen

Uges

Heijerman

et al. 2019

Brit J Clinical Pharma

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Aims We aimed to compare the pharmacokinetics (PK) and safety profile of tobramycin inhalation solution (TIS) using the I‐neb device to the standard PARI‐LC Plus nebulizer in children with cystic fibrosis. Methods A randomized, open‐label, crossover study was performed. In 2 separate study visits, blood samples from 22 children were collected following TIS nebulization with I‐neb (75 mg) and PARI‐LC Plus (300 mg). Study visits were separated by 1 month, in which 1 of the study nebulizers was used twice daily. Tobramycin PK for both nebulizers was established using measured tobramycin concentrations and Bayesian PK modelling software. Hearing and renal function tests were performed to test for aminoglycoside associated toxicity. In addition to standard estimated glomerular filtration rate values, biomarkers for tubular injury (KIM‐1 and NAG) were measured. Patient and nebulizer satisfaction were assessed. Results Inhalations were well tolerated and serum trough concentrations below the predefined toxic limit were reached with no significant differences in PK parameters between nebulizers. Results of audiometry and estimated glomerular filtration rate revealed no abnormalities. However, increased urinary NAG/creatinine ratios at visit 2 for both nebulizers suggest TIS‐induced subclinical tubular kidney injury. Nebulization time was 50% shorter and patient satisfaction was significantly higher with the I‐neb. Conclusions Nebulization of 75 mg TIS with the I‐neb in children with cystic fibrosis resulted in comparable systemic exposure to 300 mg TIS with the PARI‐LC Plus and was well tolerated and preferred over the PARI‐LC Plus. Long‐term safety of TIS nebulization should be monitored clinically, especially regarding the effects on tubular kidney injury.

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“…Designed to enhance drug delivery, TIP shortens the drug administration time and has been shown to improve patient convenience, satisfaction, and adherence [18, 19]. Although the safety and efficacy profile of TIP was similar to that of TIS over a 6-month period in a randomised, controlled study (EAGER), the administration time for TIP was significantly shorter as compared with TIS (mean 5.6 vs 19.7 min, respectively; p < 0.0001) [15].…”

Section: Introductionmentioning

confidence: 99%

Economic Evaluation of Tobramycin Inhalation Powder for the Treatment of Chronic Pulmonary Pseudomonas aeruginosa Infection in Patients with Cystic Fibrosis

et al. 2017

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BackgroundChronic lung infection with Pseudomonas aeruginosa occurs in approximately 50% of patients with cystic fibrosis (CF). This infection further compromises lung function, and significantly contributes to the increased healthcare costs.ObjectivesInhaled tobramycin, used to manage P. aeruginosa infection in CF patients, is available as powder (tobramycin inhalation powder, TIP) and solution (tobramycin inhalation solution, TIS). Evidence suggests increased adherence with the use of TIP over TIS. Hence, this analysis aimed to evaluate the potential pharmacoeconomic benefit of increased adherence with TIP over TIS in the US setting.MethodsA patient-level simulation model was developed to compare TIP with TIS. Both costs and benefits were predicted over a 10-year time horizon from a payer’s perspective, and were discounted annually at 3%. All costs were presented in 2016 US dollars.ResultsTIP was associated with greater quality-adjusted life-years (by 0.27) and lower total costs (by US$36,168) as compared with TIS over a 10-year time horizon. TIP-treated patients experienced a decreased mean number of exacerbations than TIS-treated patients (39.24 vs 50.20). Furthermore, administration of TIP via the T-326 Inhaler was associated with significant cost savings per patient, because of the nebulizer required for administering TIS (by US$1596) and exacerbation costs (by US$76,531). Probabilistic sensitivity analysis showed that TIP was dominant over TIS in 100% of the simulations.ConclusionTIP is likely to be a more cost-effective treatment than TIS, and therefore may reduce the economic burden of CF.

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Long-term safety and efficacy of tobramycin in the management of cystic fibrosis

Cited by 18 publications

References 46 publications

Fundamentals of aerosol therapy in critical care

Fundamentals of aerosol therapy in critical care

Pharmacokinetics and safety of tobramycin nebulization with the I‐neb and PARI‐LC Plus in children with cystic fibrosis: A randomized, crossover study

Economic Evaluation of Tobramycin Inhalation Powder for the Treatment of Chronic Pulmonary Pseudomonas aeruginosa Infection in Patients with Cystic Fibrosis

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