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Tobi is an aqueous solution of tobramycin for inhalation manufactured by PathoGenesis Corporation, now owned by Chiron Corporation. It is marketed as 300 mg tobramycin sulfate in 5 mL of preservative-free, sterile, sodium chloride solution with a pH of 6 in single-use plastic ampules. It is administered using a compressed air driven reusable nebulizer. It is the only solution of tobramycin approved by the FDA for inhalation by cystic fibrosis patients, although unapproved inhalation use of intravenous tobramycin products has occurred. This is a bad thing, because IV formulations of tobramycin contain preservatives (usually phenol) which irritate the respiratory system.

Tobramycin and other aminoglycosides in IV formulations have been used for many years to treat endobronchial pseudomonas aeruginosa infections in CF patients. By the age of 17, 70% of CF patients have P. aeuruginosa in their sputum cultures. This bacterium represents the major infectious burden in the airway of these patients, and the extent of the infection is often a predictor of patient mortality. Unfortunately, the effectiveness of IV drug administration for lung infections is limited, and loss of lung function in CF patients further limits the usefulness of IV treatment. Very high doses are required for IV therapy to be effective, leading to problems with ototoxicity and nephrotoxicity. Inhalation is prefered, as it gets the drug directly to the source of the infection, allowing lower doses to be used with much greater effectiveness.

Recommended dosing of Tobi is 300 mg (one ampule) twice daily in cylces of 28 days of treatment followed by 28 days without treatment. It takes approximately 15 minutes to deliver each dose. Cycling was chosen based on clinical data and animal studies involving tobramycin as well as microbiological studies of disease in the airways of CF patients. Clinical data showed that the treatment effect was maintained during the no treatment part of the cycle, cycling allows histological changes in the respiratory tract to resolve, and decreases the potential for treatment-emergent bacterial resistance.

Loss of pulmonary function accounts for more than 87% of deaths in CF patients. Most CF patients continually lose lung function, however, patients treated with Tobi typically gain lung function during treatment. After 92 weeks of treatment cycles, the average patient receiving Tobi experiences a 5% increase in lung function, with adolescents showing even greater improvement. Studies have showed that patients between 13 and 17 years old have an average increase in lung function of 14%. This is significant because teenage patients typically suffer from the highest rate of lung function loss. Even if the effectiveness of treatment with Tobi decreases over time, the increased lung function acheived early in treatment has long lasting effects and should significantly increase the life expectancy of the average patient. Nearly 50% of CF patients are hospitalized at least once per year, with an average stay of nearly 10 days due to acute pulmonary infections. During clinical trials, hospital stays for patients treated with Tobi were reduced by more than 27%, with the average stay reduce nearly two days. Also significant was an average weight gain of 11% for patients in the clinical trials (CF patients typically have trouble maintaining their weight, so weight gain is usually associated with general improvement in health).

Although clinical data suggest that treatment with Tobi can significantly improve the quality of life and life expectancy of CF patients, it is not a cure for cystic fibrosis. Hopefully Tobi along with other improvements in CF treatment can help prolong the lives of many CF patients until a cure is found.

In memory of Jenny
Hang in there Scott

Tobi Technical Monograph, PathoGenesis Corporation

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