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Mixing nebulized medications: Physical and chemical compatibility

Mixing nebulized medications: Physical and chemical compatibility
  Albuterol
(salbutamol)		 Albuterol-ipratropium Arformoterol Budesonide Fluticasone
propionateΔ		 Formoterol Ipratropium bromide Levalbuterol
(Levosalbutamol)		 Revefenacin Sodium chloride 7%§
Albuterol (salbutamol)   NR NR C C* NR C* NR NR C[1]
Albuterol-ipratropium NR   NR C*[2] NR NR NR NR NR NR
Arformoterol NR NR   C[3] NR NR C[3] NR NR NR
Budesonide C C*[2] C[3]   NR C[3] C C[4] NR C◊
Fluticasone propionateΔ C* NR NR NR   NR C* NR NR NR
Formoterol NR NR NR C[3] NR   C[7] NR C[5,6] NR
Ipratropium bromide C* NR C[3] C C* C[7]   C[4] NR C[1]
Levalbuterol (Levosalbutamol) NR NR NR C[4] NR NR C[4]   NR NR
Revefenacin NR NR NR NR NR C[5,6] NR NR   NR
Sodium chloride 7%§ C[1] NR NR C◊ NR NR C[1] NR NR  
  • Factors other than physicochemical compatibility can alter drug mass delivery profile of medication mixtures. Such factors can include increased volume placed in reservoir and potential for alteration in particle size and character of mixed solutions. Except where compatible ("C") mixtures have an asterisk (*), the effect that mixing of medications has on drug mass delivery profile, relative to separate nebulization, has not been adequately studied.
  • When mixing nebulized medications, use only freshly opened preservative free PF (ie, single-use) formulations. Mixing should take place immediately before administration.

C: compatible; NR: not recommended due to insufficient data or simultaneous use is not clinically warranted; PF: preservative free.

* For this mixture, study data are available demonstrating that aerosol particle characteristics and drug mass output are similar to those conditions when each drug is nebulized separately.

¶ Not indicated for use in children.

Δ Nebulized formulation of fluticasone is available in many countries other than the United States and Canada.

◊ Physico-chemical compatibility determined with 5.85% hypertonic sodium chloride solution.

§ Evidence of compatibility and appropriate particle size delivery for mixing sodium chloride solutions with nebulized medications is unavailable, except as described in product labels (eg, albuterol 2.5 mg/mL concentrate is diluted with 0.9% saline) and for mixtures with hypertonic saline listed above as compatible.
References:
  1. Fox LM, Foushee JA, Jackson DJ, Watson H. Am J Health System 2011; 68:1032. Visual compatibility of common nebulizer medications with 7% sodium chloride solution. Am J Health System 2011; 68:1032.
  2. Zhang R, Hu J, Deng L, et al. Aerosol Characteristics and Physico-Chemical Compatibility of Combivent® (Containing Salbutamol and Ipratropium Bromide) Mixed with Three Other Inhalants: Budesonide, Beclomethasone or N-Acetylcysteine. Pharmaceutics 2020; 12:78.
  3. 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.
  4. Bonasia PJ, McVicar WK, Bill W, Ong S. Chemical and physical compatibility of levalbuterol inhalation solution concentrate mixed with budesonide, ipratropium bromide, cromolyn sodium, or acetylcysteine sodium. Respir Care 2008; 53:1716.
  5. Siler TM, Moran EJ, Barnes CN, Crater GD. Safety and efficacy of revefenacin and formoterol in sequence and combination via a standard jet nebulizer in patients with chronic obstructive pulmonary disease: A phase 3b, randomized, 42-day study. Chronic Obstr Pulm Dis 2020; 7:99.
  6. Ngim K, Patel J. Physicochemical stability and compatibility of revefenacin (LAMA) and formoterol fumarate (LABA) inhalation solution admixture. Int J Pharm Compd 2020; 24:242.
  7. Akapo S, Gupta J, Martinez E, et al. Compatibility and aerosol characteristics of formoterol fumarate mixed with other nebulizing solutions. Ann Pharmacother 2008; 42:1416.

Adapted from: Kamin W, Erdnüss F, Krämer I. Inhalation solutions—Which ones may be mixed? Physico-chemical compatibility of drug solutions in nebulizers—Update 2013. J Cyst Fibros 2014; 13:243.

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