Guidance on what to consider when mixing nebuliser solutions and advice on which combinations are compatible.

Considerations when mixing

Nebuliser solutions should not be mixed unless there is evidence they are compatible. Compatibility studies generally involve use of preservative-free formulations, so use of these when mixing is preferable. Stabilisers and preservatives in the nebuliser admixture may reduce the effect of the medication.

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

Some manufacturer’s data state certain products can be mixed. This gives assurance there is stability data to support the admixture but it does not mean the admixture becomes a licensed product. There may also be differences between generic products in terms of excipients etc that impact a manufacturer’s compatibility advice.

Prescribing and administering

All nebuliser solution admixtures result in an unlicensed product unless the admixture is presented in a licensed formulation.

Unlicensed products cannot be administered under a Patient Group Direction (PGD).

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
  • be an independent prescriber with the legal right to prescribe an unlicensed medicine. This is currently a doctor, dentist, pharmacist, nurse or supplementary prescriber.

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

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

Always check to see if you have any local guidance on nebuliser solution mixing.

Dual combinations

Click on the relevant medicine to see which combination is compatible.

Triple combinations

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

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

Quadruple combinations

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

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

  • colistimethate + ipratropium bromide + salbutamol + fluticasone-17-propionate

Further information

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

Update history

  1. Clarified licensed status of nebuliser combinations and implications for PGDs
  1. Tool changed for accordion feature to improve visibility of information
  1. Published

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