Pulmozyme® for children under 5 years of age?

Question

Hello,
the treating physician at our CF center put the intake of Pulmozyme® (rh-DNAse) up for debate.
Our son is 3.5 years old and got rather incidentally the diagnosis of CF. He has been admitted to hospital due to complaints of asthma and bad oxygen saturation after an infection and at time of discharge a sweat test had been done routinely. This was then positive at both controls.
As our son is according to the physicians rahter an untypical case of a child with CF as he is well nourished and developed and shows few symptoms that point at CF.
Only now, after the sweat test the puzzle gets together.
Is there any experience with children under the age of 5 who have been treated sucessfully with Pulmozyme®? Are there any studies about Pulmozyme® that can be read?
Thank you

Answer

Hello,
you report that your 3.5 years-old son has been diagnosed with CF recently. The physician from the CF center addressed the treatment with Pulmozyme®. You request, if there is any experience about treatment with Pulmozyme® in children under the age of 5.
Officially, Pulmozyme® is licensed only for the treatment of children who are 5 years of age or older. This is based on the licensing studies for Pulmozyme® that have been conducted only with patients 5 years of age or older. The reason for this limit of age lies in the fact, that younger children are incapable of doing a lung function test reproducibly. In contrast to Germany and Europe, in the USA Pulmozmye® therapy is permitted for younger patients in justified single cases. At the moment, no comprehensive and scientifically evalutated experience reports exist about the long-term usage of Pulmozyme® in younger children. In Germany, it is advisable to always at first apply with a well justified request for an exeptional permission for the coverage of the costs by the insurance, as otherwise the very high costs for the drug have to be paid by the parents.
Generally, I would like to advise in your situation to do a treatment trial with NaCl solution (hypertonic saline) instead of Pulmozyme®. Here one could start at first with inhalation of 3%-NaCl. In case this will be tolerated well, one could consider a change to inhalation with 6%-NaCl.
Please discuss this with your treating physician, who knows your situation more comprehensively.
Yours sincerely,
Dr. H.-G. Posselt

07.01.2014

1.1.14
We had the question about Pulmozyme® in younger children previously, as well as the question about the sense of the usage of hypertonic saline.
Here Comes the citation of the prevcious answer:
"The existing guidelines recommend Pulmozyme® (DNAse, mucolytic agent) for patients with CF, 6 years of age or older with mild, moderate and severe lung disease. Pulmozyme® is not licensed for children under the age of 5. Therefore it is often not paid by the insurance. However, studies reveal that it is safe also in children under 5 years of age, so in some centers it is given in younger children if symptoms are relieved in the individual case. In general, it is given when there is a pulmonary involvement. An alternative, which is much cheaper is the inhalation of hypertonic saline (NaCl 5-7%) as a mucolytic agent. International guidelines recommend its use for CF patients over 6 years of age. For younger children, there is limited safety data available, so it isn’t used routinely in this age group. However, some centers (in Germany, for example) use it with good experience even under the age of one year increasing the concentration slowly from 0.9% to 6% NaCl."
Concerning Pulmozyme®, there is data from McKenzie 2007 from the epidemiologic registry, suggesting that it is safe for children under 5. A study from 2001 showed an effect of pulmozyme in younger children on the frequency of pulmonary exacerbations (see citations in paper from Smyth et al. 2010 in the European Respiratory Journal "Respiratory medicines for children: current evidence, unlicensed use and resaerch priorities"). In the clinical Trials Register (www.clinicaltrials.gov), there are 2 studies on the effectiveness of Pulmozyme® in younger children; one has too few participants, the other has the results not yet available.
Therefore, concerning Pulmozyme® usage for children under the age of 5, there is not much data, so more data is needed and afterwards also new uniform guidelines about recommendation also for this age group.

Concerning the use of Hypertonic Saline:

There is a Q/A commenting on the ISIS study, that could not show an effect of 7% hypertonic saline compared to 0.9%. However, there were some methodogical problems:
ecorn-cf.eu/index.php?id=65&L=8&tx_expertadvice_pi1[showitem]=2191&tx_expertadvice_pi1[search]=hypertonic%20saline

Another study in 2012 from Gupta et al showed however a better effect of 3% hypertonic saline compared to 7%.

There is no concrete Information for which age group hypertonic saline is licensed, the reason for this is that it has not a drug license, but a CE medical device license. We have limited safety data (Rosenfeld 2012 and Subbarao et al.), suggesting a good short term tolerability.A study from Subbarao et al. 2013 using the LCI (lung clearance index) showed an effect of 7% hypertonic saline over 0.9%.
In conclusion, here also more data is needed and a uniform consensus for the age group under 6 years of Age.

D. d'Alquen