Medicines Q&As
Q&A 100.6
Which commonly used nebuliser solutions are compatible?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
Before using this Q&A, read the disclaimer at www.ukmi.nhs.uk/activities/medicinesQAs/default.asp
Date prepared: 31st January 2012
Background
As administration of one drug by nebulisation can take 15-20 minutes, mixing nebuliser solutions
might aid compliance by decreasing nebulisation time (1).
Answer
There is little published evidence on the compatibility of nebuliser solutions. Where available, it is
preferable to use licensed combination products. The Summary of Product Characteristics for
Atrovent® (ipratropium) UDVs (unit dose vials) indicates that it can be combined with a short-acting
beta2-agonist in the same nebuliser chamber, for simultaneous administration where co-administration
is required (2). Pulmicort (budesonide) respules® can be mixed with terbutaline, salbutamol and
ipratropium (3). Unless specifically stated in the Summary of Product Characteristics, the
manufacturers of nebuliser solutions do not recommend that they are mixed and as such these
mixtures are unlicensed. In-house data from manufacturers and the limited published data suggest
that two-way mixes of some nebuliser solutions are physically and/or chemically compatible in some
cases (4-8), as the summary table below shows.
Table 1. Compatibility table of commonly used nebuliser solutions
Drug
Budesonide
Budesonide
Fluticasone
Ipratropium
Salbutamol
Terbutaline
Colistimethate
N/A
C
C
C
NI
C
C
C
NI
C
C
NI
N/A
C†
Fluticasone
N/A
Ipratropium
C
C
Salbutamol
C
C
C
Terbutaline
C
C
C
N/A
Colistimethate
NI
NI
NI
C†
C
N/A
NI
†
NI
NI
Compatible
Not applicable
No information
ensure salbutamol solution or any diluent used is preservative-free
In general, drugs should not be mixed unless there is firm evidence that they are compatible (9). If
mixing is necessary, 0.9% sodium chloride is usually used as a diluent (9,10). Solutions should be
mixed immediately prior to use (1) and using aseptic precautions (9). To maximise nebulised drug, a
minimum volume of 3 to 4mL should ideally be nebulised. This volume is required to reduce the
amount of drug that may be left in a ‘dead space’ at the end of nebulisation; although this is less with
newer nebulisers and no further dilution of commercial nebuliser solutions is necessary (10). If
turbidity, colour changes or precipitation occur, the mixture should be discarded (1). Any unused
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
solution should be discarded. Regardless of whether nebulised solutions are mixed, patients should
be monitored to ensure that the required clinical response is being obtained (1).
There is one report of chemical compatibility between budesonide and the combination product
Duovent® (fenoterol and ipratropium) mixed in a 1:1 volume ratio (7). There is no information available
for other three-way mixes of nebuliser solutions and therefore other mixes cannot be recommended.
The mixing of nebuliser solutions should only be undertaken in the best interests of the patient and
only by a person competent and willing to do so. Instructions for mixing should be in writing (11). In
most cases the mixing of nebuliser solutions is unlicensed; healthcare professionals should be
aware if a medicine is to be used outside its licence and take responsibility for its use in this manner.
Summary
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Mixing of nebuliser solutions should only be undertaken in the best interests of the patient and
only by a person competent and willing to do so. Instructions for mixing should be in writing.
Two-way mixes of nebuliser solutions have been used for a variety of respiratory medicines.
Table 1 indicates those that are deemed to be compatible.
Unless specified in the Summary of Product Characteristics, the manufacturers of nebuliser
solutions generally do not recommend that they are mixed and as such these mixtures are
unlicensed.
In most cases the mixing of nebuliser solutions is unlicensed; healthcare professionals should
be aware if a medicine is to be used outside its licence and take responsibility for its use in
this manner.
Where available, it is preferable to use licensed combination products.
Two-way mixes should be used immediately, and should be discarded if precipitation, turbidity
or colour changes occur.
The mixture may be diluted with 0.9% sodium chloride to a volume of between 3 and 4mL.
Any unused solution should be discarded.
Patients should be monitored to ensure continued clinical response to treatment.
Duovent® (fenoterol and ipratropium) and budesonide admixture have been shown to be
chemically compatible.
Data on other three-way mixes are lacking and therefore cannot be recommended.
Limitations
There is little published evidence on the compatibility of nebuliser solutions (by brand or medicine
class).
References
(1) Joseph JC. Compatibility of nebulizer solution admixtures. Ann Pharmacother 1997;31:487-8.
(2) Summary of Product Characteristics - Atrovent UDVs®. Boehringer Ingelheim Ltd. Accessed
via: http://www.medicines.org.uk/EMC/medicine/2797/SPC/Atrovent+UDVs/ on 26 Jan 2012
[Date of revision of text July 2011].
(3) Summary of Product Characteristics - Pulmicort Respules®. AstraZeneca UK Ltd. Accessed via:
http://www.medicines.org.uk/EMC/medicine/2471/SPC/Pulmicort+Respules+0.5mg+%26+1mg
+Nebuliser+Suspension/ on 26 Jan 2012 [Date of revision of text 21 July 2009]
(4) Data on File, Allen & Hanbury’s (PCN102). Obtained June 2005.
(5) Roberts GW and Rossi SOP. Compatibility of nebuliser solutions. Aust J Hosp Pharm 1993; 23:
35-7.
(6) McKenzie JE and Cruz-Rivera M. Compatibility of budesonide inhalation suspension with four
nebulizing solutions. Ann Pharmacother 2004; 38: 967-72.
(7) Kamin W, Scwabe A, Krämer I. Inhalation solutions – which ones are allowed to be mixed?
Physico-chemical compatibility of drug solutions in nebulizers. J Cyst Fibros 2006; 205-13.
(8) Burchett DK, Darko W, Zahra J, et al. Mixing and compatibility guide for commonly used
aerosolized medications. Am J Health-Syst Pharm 2010; 67: 227-30.
(9) Harriman A-M, Purcell N, Fleming S, et al. Can we mix nebuliser solutions? Stability of drug
admixtures in solutions for nebulisation. Pharm Prac 1996; Oct: 347-8.
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
(10) Gibbs KP, Cripps D. Asthma. In: Walker R and Whittlesea C. Clinical Pharmacy and
Therapeutics. 4th ed. Edinburgh. Churchill Livingstone. 2007; p381.
(11) Department of Health. Mixing of Medicines prior to administration in clinical practice: medical
and non-medical prescribing. May 2010. [cited 2012 February 24] Available from
http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@en/@ps/documents/digi
talasset/dh_116360.pdf
Quality Assurance
Prepared by
Anna Burgess, Welsh Medicines Information Centre, University Hospital of Wales (based on earlier
work by Gail Woodland)
Date Prepared
31 January 2012
Checked by
Gail Woodland, Welsh Medicines Information Centre, University Hospital of Wales
Date of check
24 February 2012
Search strategy
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Embase (“[fluticasone.exp OR salbutamol.exp OR ipriatropium bromide.exp OR
budesonide.exp OR terbutaline.exp OR colistin.exp] AND [drug incompatibility.exp OR drug
combination.exp OR drug compatibility.mp] AND [inhalational drug administration.exp OR
nebulisation.exp]” Limit: yr=2009-current, human)
Medline (“[fluticasone.mp OR ipratropium.exp OR budesonide.exp OR colistin.exp OR
terbutaline.exp OR albuterol.exp] AND administration, inhalation AND [drug incompatibility.exp
OR drug combinations.exp OR drug compatibility.mp]” Limit yr=2009-current, human)
IDIS (Drug(s): ("albuterol 12120066" ) or ("budesonide 84060022") or ("fluticasone 68040094")
or ("fluticasone furoate 68040020") or ("terbutaline 12120094") or ("ipratropium bromide
12080028") or ("colistin 8122889") and Descriptors: ("incompatibility physical 33" or
"incompatibility chemical 34" ) and "adm inhalation 98". Limit Years 2009-2012)
In-house database (MiDatabank)
Micromedex (DrugDex, Martindale)
Electronic Medicines Compendium
NeLM (nebulis* AND incompatibil*)
BNF
Available through NICE Evidence Search at www.evidence.nhs.uk
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