Amiloride Inhalation

Question

My ten-month-old son suffers from CF. He has lung problems and inhales amiloride. I have read on your advisory pages that amiloride has practically fallen out of use abroad because insufficient research has been done on its effects on CF patients. Why is this medicament so widely used in our country? Can you suggest another, more suitable alternative to amiloride or tell me what types of inhalation medicaments are used abroad?

My second question concerns the administration of Creon 10000. We administer the medicine according to my son´s weight (9kg, therefore 9 capsules a day) and the medicine is administered in five portions of food. Should the amount of pancreatin derive from the amount of food or from the amount of fat that the food contains? How many grams of fat does one granule of pancreatin help digest when the patient has dysfunctional pancreas?

It is usually stated that pancreatin is not necessary when the patient eats fruit. Does this also hold true for the following: bananas, avocados, cooked fruit or preserves, or pure fruit with added maltodextrine? Thank you for answering my numerous questions.

Answer

Hello,
You are correct to note that amiloride isn´t used abroad. The reason for this is that amiloride has a very short self life and would have to be inhaled many times a day to have a proper effect, which isn´t possible. Data available on the inhalation of amiloride is not so convincing at the moment, that it is recommended as a standard therapy internationally. As the experience we have here in the Czech Republic shows a positive impact, scientists are working on its powder form at the moment. Patients should be able to inhale this powder in the same way as asthmatics inhale various powder medicines.
In our country, amiloride is popular because it is well tolerated by patients. It doesn´t cause irritation and it doesn´t have an unpleasant taste. Cystic fibrosis involves defects of water and chloride transmission through cell walls. Amiloride prevents absorbtion of sodium from the liquid covering airway surface. It helps to preserve not only sodium but also water in this liquid and this way the secretion becomes diluted. We are fully aware of amiloride´s short-term effect but as physiotherapy and airway clearing immediately follow inhalation, its potential is still well used.
There are mainly two other medicaments that influence mucus properties. Indisputably the most effective one is recombinant DNase, which is sold under the name of Pulmozyme®. The immune system reacts to airway infection by releasing a great number of leukocytes into the airways. After a certain period of time, the leukocyte cells fall apart and release their deoxyribonucleic acid (DNA), which considerably thickens mucus. DNase breaks apart the acid and dilutes mucus in the process. This treatment, however, is not recommended for children under six years of age as there is no data on the efficacy of it in this age group. Data on the security of DNAse inhalation shows that it is safe in this age group. Even though it is administered to some children under five if their airways are heavily filled with mucus, it is uncommon. In CF patients, six years of age or older, however, DNase is even recommended if they have only mild lung disease or are asymptomatic to improve lung function and reduce exacerbations. In patients with severe lung disease, its use is even strongly recommended.
In recent years, inhalation of 5 – 7% NaCl (sodium chloride, or, in other words, salt) solution has become widely popular. Its chronic use is recommended by international guidelines for CF patients six years of age or older to improve lung function and to reduce exacerbations. For younger children, there are limited safety data and it is not licensed so far. Therefore, it isn’t used routinely in this age group. However, in Germany, for example, it is used in some centers with good experience even under the age of one year, when starting with a concentration of 0.9% (physiological NaCl solution) which is increased slowly to 5,85%. It is generally stated – and our practice has proved it as well – that this solution might cause considerable irritation. Therefore, it might be necessary to inhale substances widening the bronchi before its inhalation. Otherwise the bronchi might narrow and a condition similar to an asthma attack might occur. Some patients are very happy with salt – others, however, find its solution hard to tolerate as they find it irritating and far too salty.
Other medications – so-called mucolytics or mucus dissolving substances - are very popular, but their effect is rather questionable. They aren´t recommended for long-term use, as they irritate mucus-producing cells in the airway mucous membranes.
However, physiological solutions, like physiological NaCl 0.9% can be inhaled to moisten the mucosa. There is a special type of salty mineral water – Vincentka® –that is often used for inhalation. This kind of mineral water, however, is a hypotonic solution with a NaCl content of 0.24%. Furthermore, it is not a sterile solution (as is the prescribed 0.9% NaCl solution, which is a well controlled medical product). Admittedly there has been a microbiological investigation (laboratory report 2007) which did not show any harmful germs such as E. coli and Pseudomonas; however, one cannot be sure how often those controls are performed on this water. There are no studies about the safety and efficacy in CF patients. Therefore it cannot be recommended as a standard inhalative therapy.
In summary, depended on the experiences that your treating CF center has made on inhalative substances at the age of your son, they will recommend a certain therapy for you. If it should turn out that this therapy isn’t working well, there are some possibilities that can be tried even at that age group; please talk to your treating physician about this.
As for your question about Creon, an appropriate dose is hard to determine. To give you a rough idea of how the right dosage is found: the aim is to keep lipase intake below 10000 units per kg body weight per day. The dosage depends on the fat intake with the food, however, it can vary widely between 500 and 4000 IU lipase per gram of dietary fat. The dosage is increased according to the presenting clinical symptoms: it is important that your child gains weight and has as normal stool as possible in terms of amount, appearance and smell, and doesn´t suffer from stomach aches.
Larger doses of Creon need to be taken when your child eats foods with higher fat content. Smaller doses should be taken with breakfast and snacks – portions are usually smaller at these times, and less fat is usually eaten.
Creon doesn´t have to be taken with fruit (fresh or cooked) if the fruit is pure and without any other added substances. This means that if maltodextrine is added to the fruit, Creon should be taken. Bananas are the only type of fruit which we recommend Creon to be taken with.
Dr. J. Brázová and Dr. D. d'Alquen

13.12.2011