Tolerability of Cayston®

Question

Hello,

I have CF and asthma and therefore I inhale Cayston® (Aztreonam lysine) every second month (intolerability of Tobi® (Tobramycin inhalation solution) and Colistin)). I tolerate Cayston® better but only if I dissolve it with 0.9% NaCl and not with 0.17% sodium chloride solution enclosed by the company (cough and burning during inhalation, increased constriction).
Is the effect garantueed even so? The amount of sputum decreases clearly in the third and fourth week.

Answer

Dear questioner,

You are asking whether Cayston® (Aztreonam lysine) can also be prepared for inhalation with 0.9% NaCl instead of 0.17% NaCl without losing its efficacy. We asked the producer of Cayston® (Gilead Sciences GmbH) directly: In certain particular cases where it is justified it is possible to prepare the Cayston-inhalation-solution with 0.9% NaCl solution as well. The effectiveness and stability of the solution prepared this way is not changed markedly, at least if used immediately. However, it has to be considered that, when using 0.9% NaCl, the osmolality of the inhalation solution clearly increases compared to the osmolality which was tested in the clinical approval studies where 0.17% NaCl was used. This, in turn, can cause an increased frequency of side effects, e.g. cough. In your case this is obviously not the case (?).
Furthermore it should be taken into account that the chamber of the Altera™ nebulizer (nebulizer that is provided with the Cayston® package) only contains a little bit more than 1ml of liquid. If a greater amount of 0.9% NaCL solution is needed for the preparation of the single inhalation dose, several inhalation steps might become necessary to nebulize that whole solution.

In any case it has to be pointed out that this application is not within the range of the approved indication of Cayston® and therefore cannot be recommended. The individual application should be discussed with your CF doctor.

Please let me give you some background information about the use of 0.17% NaCl solution for the reconstitution of Cayston® (preparation of inhalation solution with the Cayston® powder):
When developing a certain product for inhalation, one of the critical parameters of the solution is its osmolality (the upper limit of the osmolality of a nebulized inhalation solution is seen at about 500mOsm/kg. A too high osmolality reduces the tolerability of the product).

Since in the development of Cayston® the volume to be inhaled was supposed to be kept as low as possible in order to allow for a very short inhalation period (ca. 1 ml of liquid after reconstitution), using 0.9% sodium chloride solution with unchanged volume would have resulted in significantly increased osmolality and therefore most probably also in reduced tolerability.
In order to avoid this, the volume of the inhalation solution would have had to be doubled to inhale 75 mg of Cayston® which in turn would have meant a signicantly prolonged inhalation period.

Best regards,
Dr. Christina Smaczny

14.03.2013