Mixing nebuliser solutions is often done but rarely licensed. Compatibility of these solutions have been studied and are outlined below, along with a handy tool

Mixing nebuliser solutions

Nebuliser solutions should not be mixed unless there is evidence that they are compatible. Compatibility studies generally research preservative-free formulations, and mixing with these is preferable. It has been shown that the presence of stabilisers and preservatives in nebuliser combinations reduces the effect of the medication.

Mixing should be done immediately before administration, and any remaining admixture should be discarded. If turbidity, colour changes, or precipitation occur, the mixture should be discarded.

Stability of combined nebuliser solutions

Combining different nebuliser solutions can affect the chemical stability, particle size, and distribution of the medicine through the lungs. If mixing is required, the mixture should have been tested for chemical and physical compatibility before administration.

Licensed combinations

Licensed combinations of nebuliser solutions are always stated in the Summary of Product Characteristics (SPC). Whenever possible, licensed combinations should be used.

Commonly used licensed combinations

Ipratropium bromide containing

Ipratropium bromide can be combined with a short acting beta2-agonist (e.g. salbutamol) where co-administration is required.

Budesonide containing

Similarly, budesonide nebules can be mixed with terbutaline, salbutamol, sodium cromoglicate or ipratropium bromide, as long as the admixture is used within 30 minutes.

Unlicensed combinations

Unless otherwise stated, all resultant combinations of nebulised medicines are unlicensed.

If prescribing an unlicensed medicine, you must:

  • be satisfied that there is sufficient evidence or experience of using the medicine to demonstrate its safety and efficacy
  • take responsibility for prescribing the medicine and for overseeing the patient’s care
  • make a legible record of all medicines prescribed and your reasons for prescribing an unlicensed medicine

If you are administering an unlicensed nebulised combination, you must keep a record of:

  • how you have combined the nebulised solutions
  • what nebulised solutions have been combined

Three-way combinations (unlicensed)

This is typically used as therapy for cystic fibrosis (CF). A number of these combinations have been found to be compatible, including:

  • salbutamol combined with tobramycin and ipratropium bromide
  • salbutamol combined with ipratropium bromide and dornase alfa, when all solutions are preservative free
  • budesonide combined with fenoterol and ipratropium bromide

Four-way combinations with colistimethate (unlicensed)

During resistant infections, people with CF may require inhalation treatment of colistimethate with standard inhalation therapy.

The following four-way combination is compatible when preservative free solutions are used:

  • colistimethate, ipratropium bromide, salbutamol, and fluticasone-17-propionate

Compatibility tool

The tool below identifies if two nebuliser solutions are compatible when combined in one nebuliser. To use this tool, select which nebuliser solutions are being combined.

These two nebuliser solutions are compatible to be mixed and nebulised together.

Check local guidelines for more information and how to mix nebulised solutions.

Compatibility does not equate to licensing – check the SPC for licensing before administering.

There are reports of compatibility between these two nebuliser solutions.

Check local guidelines for more information and how to mix nebulised solutions.

Compatibility does not equate to licensing – check the SPC for licensing before administering.

There is insufficient evidence to demonstrate compatibility of these two nebuliser solutions.

These two nebuliser solutions are not compatible and should not be mixed together.

Only branded Tobi® or Bramitob® formulations of tobramycin are compatible to be mixed with dornase alfa.

Only preservative-free formulations of ipratropium bromide (e.g. Atrovent®) are compatible with sodium cromoglycate.

Please select a different second nebuliser solution.

There is therapeutic duplication here and there is no need to give these two nebuliser solutions together.

Contact Details

For further information or advice on mixing nebuliser solutions, please contact your local medicines information service.