Aerosols

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Contents:

  • Bronchodialators
  • Anti inflammatories
  • Mucolytics
  • Antibiotics
  • DNASE (generic) OR PULMOZYME (brand name)
  • Bronchodialators

    These work by relaxing the muscles in the bronchial tubes making breathing easier. They are used for asthma-type symptoms such as wheezing, chest tightness, bronchospasm, etc. For use in a nebulizer these drugs must be diluted with normal saline or another aerosol med such as Intal, Atrovent or an antibiotic. Bronchodialators are also available in metered dose inhalers (MDI’s). These are the small, hand held spray type inhalers, which may be used with holding chambers to increase their effectiveness. Some types of holding chambers are the Aerochamber, InspirEase and Inhalaid. A holding chamber also makes it easier for a child to use a MDI effectively.

    Brand and generic names of commonly used inhaled bronchodialators include albuterol sulfate (Proventil, Ventolin–brand names), metaproteronal sulfate (Alupent), bronkosol and Isuprel. Albuterol seems to be the most commonly used these days. A new inhaled bronchodilator which lasts 12 hours is called Seravent, this is only available as an MDI as far as I know. Tornalate is a fast acting bronchodilator and has a duration period of about 5 hours in most people. Tornalate is a beta-agonist bronchodilator distributed by Dura Pharmaceuticals in the United States. The generic name is bitolterol mesylate. As the product labeling information is in the 1995 Physicians Desk Reference, one can read the prescribing information directly or ask your pharmacist for patient-specific information.

    Bitolterol has very little bronchodilator activity until it is hydrolyzed in the tissues (or blood) to colterol. Colterol is similar to drugs PWCF are familiar with such as albuterol and isoproterenol. After an inhalation of this drug, bronchodilation begins in about 5 minutes and is expected to last 4-8 hours on average. Patients with hypertension (high blood pressure), diabetes, certain types of heart problems need to exercise caution in using this drug. Patients should also not be taking other drugs in the same pharmacologic class.

    Atrovent is an anticholinergic bronchodilator (the others mentioned above, e.g. albuterol, etc, are beta-adrenergic). Atrovent is related to atropine, it is slower acting than the beta-adrenergic (adrenaline-like) bronchodilators, taking about 30-60 minutes to peak. Atrovent is also not as potent as these other type bronchodilators, but may be useful in treating excessive mucus or bronchitis. It may be used concurrently with albuterol in a nebulizer. Atrovent is also available as an MDI.

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    Anti inflammatories

    These drugs act in the lungs to reduce inflammation. They are preventative type meds, and must be used regularly to be of use.

    Cromolyn Sodium (brand name–Intal) this is a non steroidal anti-inflammatory, it provides no bronchodilator type effect. It is available as a nebulizer solution, and may be mixed with albuterol. It is also available as an MDI.

    Nedocramil sodium (Tilade), this is similar to Cromolyn sodium, but is only available as an MDI so far as I know. My CFer refused this one because of bad taste.

    Inhaled Corticorsteroids also reduce inflammation, they help prevent and stabilize asthma symptoms. They are only available as MDI’s, no nebulizer solutions are available that I know of. Some brand and generic names are beclomethasone (Vanceril and Beclovent), flunisolide (Aerobid), and triamcinolone (Azmacort). There are no long term side effect that have been clearly linked with the use of inhaled steroids, unlike oral steroids such as prednisone.

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    Mucolytics

    Mucolytics are drugs that destroy or break down mucus. Mucomyst (acetyl cysteine) used to be used, I haven’t heard of being used much lately. It is reported to smell like rotten eggs, not real popular with the kiddos.

    Antibiotics

    Note that any injectable antibiotic can be used as an aerosol. The most commonly prescribed antibiotics for aerosol use seems to be Tobramycin (NEBCIN, aka Tobra), Colistin (coly-mycin or coly), and Gentamicin (aka Gent). Also used are: Ticarcillian(Ticar); and “high-dose” Tobramycin (600 mg twice a day). Augmentin, Gentamicin & Tobra are reported not to have improved infection with Providencia Stuartii; Gentamicin & Tobra are reported to be generally effective with gram-negative bacteria.

    Tobra smells bad, Gent is reported to cause extreme nausea and headaches, and Coly is a pain to use because it foams up in the nebulizer so bad. It has to be mixed with sterile water because it comes in powder form. If the mixed solution is allowed to sit in the refrigerator for a while it doesn’t foam up so much. Also the Ultrasonic nebulizers (one brand is Aerosonic by DeVilbiss) are reported to be more efficient in delivering these aerosolized antibiotics–especially the Coly.

    All these aerosol antibiotics are expensive, and some insurance companies are reluctant to cover the cost, because they are intended to be used for injection. Point out to them that the cost is less than IV antibiotics and/or a hospital admission. In some cases, using aerosol antibiotics can avoid IVs.

    Tobramycin Aerosols (5/97)

    A typical dose of Tobramycin via aerosols is 80 ml twice a day. This may be prescribed for daily use, or just during exacerbations. Some clinics usually prescribe 80 ml three times a day, or perhaps 160 ml twice a day. There is not yet a standard treatment.

    “High-dose” Tobramycin aerosols means 600 mg twice a day (a preservative-free preparation was used) for 2 or 3 weeks duration during times of increased lung infection (see “Efficacy of aerosolized tobramycin in patients with cystic fibrosis” by B. W. Ramsey, et al., New England Journal of Medicine 328(24):1740-6, 1993 June 17). This may postpone the need for IV antibiotics for 1-2 years. Tobra is ineffective against Staph, thus an additional antibiotic may be needed. Tip on administration: use a high flow nebulizer if you’re using the 40 mg/ml solution. Otherwise you’ll be attached to that small volume nebulizer (note the name–there’s a reason for it!) for an hour or more each treatment. If you use the powder, you can mix that up in 10 cc of fluid, and some small volume nebs can handle that amount in 10 – 15 min. A Devilbiss ultrasonic neb is reported to take about 20 minutes to complete 600 mgs.

    Some people find that inhaling Tobramycin is irritating to the lungs and may cause a coughing reflex. That is why mixing it with proventil or some kind of bronchodilator is often recommended. Do not mix the Tobramycin with Intal; this forms a milky white precipitate (that is to say, it reacts chemically). Using a puff nebulizer of proventil either just prior to or after inhaled treatment of Tobramycin will *not* help eradicate the antibiotic’s sometimes harsh irritation.

    Tobra has previously been (and may still be, unless you educate your doctor) ordered for inhalation in the small 2 cc vials containing 80 mg of Tobra (it says Tobramycin sulfate for injection USP for IV or IM use. NDC# 0003-2725-10). A disadvantage of nebulizing this form of Tobra is the bad taste, and the bad smell that fills the area. The smell is caused not by the Tobra but by the phenol, a preservative added to this form of Tobra. It has been reported that the phenol sometimes has unwanted side effects such as coughing /wheezing etc.

    Want to avoid the bad smell/taste? The brand of Tobra made by Eli Lilly is called NEBCIN. It comes in both liquid and powder form. The powder form is preservative-free (sterile tobramycin sulfate, NDC# 0002-7040-01). It comes in 1.2 gram bottles, which must be mixed with half sterile water and half normal saline (or just sterile water or just sterile normal saline). The half and half seems to be the most often recommended (the 0.45% saline comes in an IV bag which is ordered from the pharmacy with the powder NEBCIN; also get a 30 ml syringe for each bottle, and a 2 cc — or other appropriate-sized syringe depending on the amount to go in the nebulizer — for each dose). If your current pharmacy can’t seem to order this (some are less well trained than others), use one of the CF pharmacies listed in the FAQ.

    The bottle calls for 30 ml of liquid, yielding a solution of 40mg/ml, but it may be mixed with as little as 10 ml or further diluted. After dilution, it is stable for 24 hours at room temp, or 96 hours (four days) in the fridge.

    Unfortunately, when using lower doses, such as 80mg (2 ml of 40mg/ml solution) twice a day, the end of the Tobras useful life (96 hours refrigerated) arrives when the bottle is only half empty. This is an expensive drug, yet if you don’t toss it, you risk using less effective drug, which may not work, may increase the possibility of resistance in the bugs (because they are seeing less and less Tobra, perhaps down to survivable levels), or may have other undesirable side effects. A pharmacist says that to avoid wasting the solution, draw it up into dose-sized plastic syringes and freeze them in a zip-lock bag for up to one month from dilution. One person doing this reports calculating how much of the reconstituted vial will be used in the 96 hour period, then drawing up and freezing the rest as described. DO NOT FREEZE THE VIAL (or bottle) — the glass may break, and it will all be thawed at once defeating much of the purpose.

    Tobi is a form of Tobra being developed made by Pathogenesis specifically for inhalation (not on the market yet). It will be much cheaper than the injectable forms now available. Also, it is premixed AND stable over a much longer period. Unfortunately it is reported to have the bad taste/smell problem.

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    DNASE (generic) OR PULMOZYME (brand name)

    BY GENENTECH

    The way in which Pulmozyme works is that it breaks up the strands of DNA that are part of our mucus. This makes the mucus less viscous and it comes up more easily. From CYSTIC-L discussions (see samples below) it’s obvious that DNase doesn’t work for everyone – even within the subgroup for whom it is supposed to work best. Considering all the differing views about what Pulmozyme has done and or can do for people, anyone considering the use of this drug should discuss and weigh the benefits, costs (not just monetary) and risks with their Doctor.

    In young kids or toddlers: Genentech could not study the drug because the classic pulmonary function tests (the golden standard) cannot be done. Nobody could agree on what would be a quantifiable and sturdy way to monitor the results. The company is currently starting up such a study, with other markers (in UK I believe…). On a theoretical basis, a doc should not order Pulmozyme at this time to anyone under 5 yr old.

    Refrigeration?

    This product must be refrigerated at all times. The problem is that there is no way of knowing if your Pulmozyme is effective by the time it reaches you. The question arises whether this could account for some of the inconsistent benefits from patient to patient? Maybe some refrigerators aren’t providing Pulmozyme’s required 2-8 degrees Celsius ambient storage temperature. For almost a year I’ve been spending time and money using Pulmozyme that DID NOT meet Genentech’s refrigeration specifications. Most of the time when I get my Pulmozyme, it’s just thrown in a bag with a dozen other medications. I’d never received training on the usage or handling of Pulmozyme. I can read the box like most of my medications I refrigerate only after breaking the seal.

    Dr. David Graves at Genentech recently said that if Pulmozyme is left unrefrigerated for a total of 24 hours it should be discarded. A little box containing a monthly supply costs about $1,000.00. Some CF patients are urging Genentech to make their warning clearer and perhaps modify packaging to ensure freshness.

    Sequence of Pulmozyme with other medications/treatments The conditions of the Pulmozyme studies generally attempted to mimic real-world use of the drug and therefore, did not specify the sequence order of other medications that patients with cystic fibrosis were taking. Thus, the following are unknown with regard to the sequence of Pulmozyme therapy: the effect of changing the sequence of medications in people with cystic fibrosis taking Pulmozyme, the relative effect of airway clearance techniques performed prior to or after inhalation of Pulmozyme, and the best sequence to insert Pulmozyme therapy into one’s daily routine of medications and activities. Currently, each cystic fibrosis caregiver, along with the family and the person with cystic fibrosis should carefully evaluate the response to therapy, but also consider how best to incorporate all the therapies into the daily schedule.

    Does It Matter Which Neb/Compressor Combination I Use?

    Short Answer: Yes. Only these combinations of nebulizers and compressors have been established as safe and efficacious for Pulmozyme therapy (i.e., and are therefore listed in the drug’s package insert): (1) disposable jet nebulizer Hudson T Up-draft II in conjunction with a Pulmo-Aide compressor, (2) disposable jet nebulizer Marquest Acorn II in conjunction with a Pulmo-Aide compressor, (3) the reusable Pari LC Jet+ nebulizer, in conjunction with the Pari Proneb compressor.

    These systems were not tested in other combinations. Using the Pari nebulizer with other compressors is not recommended. The seriousness of using nebulizer-compressor systems with proven efficacy and safety with respect to a particular drug became obvious to the FDA during their approval of an aerosolized drug for AIDS patients. The drug worked only in the nebulizer-compressor system which is now specified in the drug’s package insert. Remember that Pulmozyme is a protein with enzymatic activity. Small molecules (chemical-type drugs) can take a lot more abuse in general than proteins.

    Can I Reuse Nebulizers With Dnase? Can I Use the Same Neb For Dnase and for Other Drugs?

    Short Answer: No. The disposable nebulizers are labeled by their respective manufacturers for single patient use only; therefore clinical trials with Pulmozyme followed manufacturers instructions. In clinical practice, some CF centers have recommended re-use of these disposable nebs outside of these recommendations. Areas of confusion for PWCF have included: 1) differing instructions for cleaning; 2) how long to re-use their disposable nebulizer; and 3) differing instructions on whether to assign different nebs for different drugs. As the disposable nebulizers are labeled for single use only, the manufacturers can not provide information for multiple use. Due to the lack of info, CF clinicians have made the cleaning and length of use recommendations to their patients based on past experience. The directions to use separate nebs for each drug is based on the lack of info on residual drug that can be physically stuck to or absorbed into the plastic. So to be safe (limit the possible drug interactions), PWCF re-using these one-time use nebs have often been told to use separate nebulizers for their drugs.

    The Pari is a reusable neb (6 months) and the company provides instructions for cleaning. As a reusable neb, it was designed and tested for multiple use with multiple drugs.

    Can I Mix Dnase With Other Meds in a Neb?

    Short Answer: No. The Pulmozyme package insert has a statement that Pulmozyme should not be either diluted or mixed because of possible physiochemical and/or functional changes in either Pulmozyme or the other drugs. The results of some specific tests done with metaproterenol (Alupent), albuterol (Proventil), cromolyn (Intal) and tobramycin were presented at the 1994 NACFC in Orlando. The problems for mixing drugs with Pulmozyme included loss of enzyme activity, structural changes in the protein, and precipitation of the drug.

    DNASE: Rave Reviews!

    My son responds *extremely* well to DNASE. This was noted even by the doc doing the study before it was approved. So we know his reaction to it is better than “typical”, but we *swear* by it. If for any reason, and this has happened a couple of times, he goes off of it, we head right into a lung infection. He was getting it both morning and night originally, but during the waiting period for FDA approval, it was decided that once a day was as effective as twice a day. This is *not* true with (my child), but we are not pushing it because he is doing so well just on the one dose…which he usually does at night.

    Dnase has been beneficial for our fifteen year old daughter. Since starting the medication in Jan. 1994 she has been coughing considerably less and needed antibiotics only twice last year. This was a remarkable improvement.

    My 11 year old has been on DNase/Pulmozyme for roughly 2 years – having been on the clinical trials also. Until he went on it, he had been on a downward spiral. In less than a year, his lung volume had dropped from 95% to 55 – 60%. He’d been in for several cleanouts. When they put him on Dnase, he was just out of the hospital so volume was between 65 – 70%. In 7 days, it increased to 80%. In 14 days, it increased to 85 – 90 %. He has been on it since and has been out of the hospital the whole time. He previously was on CONSTANT antibiotics without which he would INSTANTLY get an infection). He now takes antibiotics periodically, more like the way my non-CF children do. He usually does his Dnase in the afternoon or evening – depending on our schedule – but has done it in the morning too. It has not seemed to matter in the least for him. We were told that it was up to us to find a time that worked for us – that it really should not matter that much, especially if he does PT 10-15 minutes after it. So he does his flutter shortly afterwards and gets up an incredible amount of gunk. In the words of a 9 year old boy (when he first went on it), “This stuff is cool, Mom. The junk is more slippery when I get it on me so I can wipe it off better.” It doesn’t work for everyone, but for CFers like my son, it has been an absolute life saver.

    Dnase has done wonders clearing out my sinuses. Ever since I began taking the drug, breathing through my nose has not been a problem. Mucus is much easier to cough up. I take two doses a day, morning and night.

    Our 9 year old daughter started on DNase one year ago and the turn-around in her health was immediate and dramatic. She had just been in the hospital for a 15 day tune-up. After we went home she started to slip back quickly (a couple of weeks). The clinic here is very conservative about DNase and they tried other things. Finally, after nearly a month my wife got a prescription, a two-week trial. The first time she used it she managed to cough up some stuff that the whole family had been trying to move for three weeks. After the initial two weeks her PFTs were up 20%, back into the normal range for her height and weight for the first time since I could remember. Her PFTs have not deteriorated back but what is extra important is that life in general has improved. She used to spend a lot of time at night coughing – some nights incessantly – but something was not clearing. She would lose sleep and this would become a viscous cycle. In our case we knew what we were doing wasn’t working, our daughter had slipped off of some plateau of health and we tried it and got lucky.

    I’m blessed my FEV1 is greater than 61 as of 01/23/95 but before Pulmozyme it was 44. Since being on Pulmozyme my FEV1 has gone up each clinic visit BTW FVC has gone from 74 pre-Pulmozyme to 87 after being on Pulmozyme. I’ve been blessed with moderate health but I can’t believe what Pulmozyme has done for me.

    DNASE: Pans

    Regarding negative effects, when my son was in the hospital January of 1994 he had a pretty normal cleanout. He was put on O2 just at night for a couple of nights, but that was it. When he left the hospital we were all excited because he was put on DNase and there were high hopes for real improvement. He was back in the hospital in June when he was put on O2 all the time. The only thing that was different in those 6 months was the DNase. He had developed Aspergillus as well (which the docs were at a loss as to how to treat so it wasn’t treated for several months. I always suspected that DNase had something to do with all of this because the doctors were completely dumbfounded by it all.

    I was in one of the DNase studies in summer/fall 1993. My FEV1 is