Consider Nebulized Drug Compatibility

Vol. 20 •Issue 18 • Page 9
Tips on Practice

Consider Nebulized Drug Compatibility

A significant number of common drugs are nebulized in the field of respiratory care. Like old die-hard RTs, some of these drugs have been around for many years, if not decades. Although many doctors routinely prescribe multiple nebulized drugs, there has been relatively little research done to determine their physico-chemical compatibility and aerodynamic behavior when nebulized together.

Conversely, parenteral (intravenous) and enteral (gut) drug admixture research has been quite extensive. This discrepancy is somewhat surprising because millions of nebulized drug admixture treatments are given throughout the world each year. Furthermore, some surveys have determined many patients disregard medical advice to not admix incompatible or potentially incompatible nebulized drugs.

Lacking research and recommendations in this area, there is no clear consensus even among clinicians about which drugs are compatible or incompatible. For that reason, compatible drugs that can be co-nebulized are sometimes given separately (or in a different nebulizer) whereas drugs that are clearly incompatible may be nebulized together (or nebulized separately but in the same nebulizer).

Incompatible drugs should not be nebulized in the same nebulizer because there is always some residual drug left following a treatment. That is why nebulizers should be labeled accordingly.

Drug Incompatibility Lingo

As you know, drug incompatibilities may result from inadequate solubility or acid-base (chemical) reactions, oxidation reactions, photolysis, hydrolysis and warm temperatures. Visual evidence of drug instability or incompatibility that you might readily see is foaming, cloudiness, crystallization, precipitation or discoloration.

Chemical incompatibility might cause irreversible degradation of drugs and render them therapeutically inactive or otherwise toxic. Drug admixture incompatibility may not be visually evident, however. Just because drugs appear to mix together and produce an aerosol does not necessarily mean they are compatible.

Theoretically, any injectable drug can be administered via inhalation if it is diluted accordingly. In respiratory therapy, inhaled drugs are usually diluted with 0.9 percent saline to optimize their pH, reduce their concentration and make them iso-osmolar. Otherwise, the undiluted drug might irritate the airway and cause cough or bronchoconstriction.

Aerodynamic Behavior Modification

Besides needing more definitive information about which nebulized drugs are compatible, caregivers also need to determine the aerodynamic behavior when nebulized drugs are admixed. Long ago it was established that the optimal mass median aerodynamic diameter (MMAD) of an inhaled drug particle size is 3 to 5 microns.

Inhaled particles larger than 5 microns may become deposited too high in the airways, and particles smaller than 3 microns may be exhaled or deposited too deeply. This is why drug manufacturers tend to focus on developing inhaled drugs that have aerodynamic characteristics that will help facilitate optimal drug deposit and therapeutic efficacy.

Drug manufacturers, however, do not design their drugs so they will retain their aerodynamic behavior and characteristics when admixed with other drugs. Research has shown that the aerodynamic behavior of some drugs can be significantly altered when they are nebulized together. Much of this research has focused only on admixing any two of the more commonly nebulized drugs.

In reality, patients are often given nebulized treatments with more than two drugs. Research has shown that when albuterol (the most popular nebulized drug) is nebulized with only one other supposedly compatible drug, the aerodynamic behavior and output of the aerosol characteristics is markedly affected.

Beyond conducting research of the aerodynamic behavior of admixtures of nebulizable drugs, researchers will also have to demonstrate what occurs when different common nebulizers are used. Recommendations can then be given for which nebulized admixtures are physico-chemically compatible without significantly altering their aerodynamic behavior and which nebulizers and flow rate can be used.

One of the goals with this type of research should be to try to develop a complete nebulized drug compatibility poster chart similar to the parenteral drug compatibility charts that are seen within clinical areas. During my search for information on this topic, I came upon a couple of tables about nebulized drug compatibility. I combined that information with some of my own and came up with a compatibility table.


1. Berlinski A, Waldrep JC. Nebulized drug admixtures: effect on aerosol characteristics and albuterol output. J Aerosol Med. 2006 Winter;19(4):484-90.

2. Desager KN. Osmolality and pH of anti-asthmatic drug solutions. Agents Actions. (1990 Nov; 31, 3-4: 225-8).

3. McKenzie JE, Cruz-Rivera M. Compatibility of budesonide inhalation suspension with four nebulizing solutions. Ann Pharmacotherapy. (2004; 38: 967-72).

4. Newton DW. Physicochemical determinants of incompatibility and instability in injectable drug solutions and admixtures. Am J Hosp Pharm. (1978; 35: 1213-22).

Nebulized Drug Table Sources

1. Nebulized Medication Compatibility:

2. Kamin W, et al. Inhalation solutions: which one are allowed to be mixed? Physico-compatibility of drug solutions in nebulizers. J Cystic Fibrosis. (2006; 5: 205-13).

Michael Hahn is a California practitioner.