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N-Acetylcysteine (NAC) for the prevention of aminoglycoside associated ototoxicity in children with cystic fibrosis

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Aminoglycoside antibiotics are used in the management of infection in children with Cystic Fibrosis.  Associated adverse effects include renal and ototoxicity, the risks of which are increased with prolonged or repeated exposure.  A number of strategies are embedded in to practice at RHC to minimise the risk, including regular audiological screening, routine monitoring of renal function and therapeutic drug levels.  More recently a screening programme for m.1555G>A change has also been introduced to identify patients at increased risk of developing aminoglycoside induced ototoxicity.  Various CF treatment centres around the UK also now include the use of N-acetylcysteine (NAC) in the routine management of patients’ receiving aminoglycosides due to the oto-protective action. 

N-acetylcysteine belongs to the thiol group of medications.  It serves as a precursor of intracellular free cysteine, used by the cells to synthesise glutathione peroxidase (GSH-Px). Although the exact mechanism of action is unknown, it is thought that the increase in GSH-Px aids in the removal of free radicals, reducing resultant oxidative stress associated with aminoglycoside ototoxicity.

Use of N-Acetylcysteine in RHC

The use of N-acetylcysteine should be encouraged in all CF patients receiving intravenous (IV) aminoglycosides at RHC.  NAC should be administered with each course of treatment for the duration of the IV aminoglycoside course. 

Dosing and administration for patients on IV aminoglycoside therapy:







< 12 years




Twice daily



Administer for the duration of the IV aminoglycoside course

1st line:

Effervescent tablets, 600mg


Tablets can be dispersed in water, orange or blackcurrant cordial.

Alternatively they can be split and swallowed without dispersion.

12 years and over


2nd line:

Injection 200mg/ml

Injection can be given orally.  Mix with water, orange or blackcurrant cordial to a concentration of 50mg/ml.







NAC for patients on nebulised aminoglycoside therapy

Routine administration of N-acetylcysteine during courses of nebulised aminoglycoside therapy is NOT recommended.

Serum concentrations following nebulised therapy are generally negligible and this route of administration is not associated with risk of ototoxicity.  There may be some clinical situations where NAC is offered to patients during prolonged courses of nebulised aminoglycoside therapy.  The following clinical scenarios require consideration:

  • Prolonged nebulised aminoglycoside therapy where the patient has reported signs of cochlear or vestibular toxicity
  • Patients requiring nebulised aminoglycoside therapy, where a degree of ototoxicity has been identified through audiology screening
  • Patients requiring prolonged nebulised aminoglycoside therapy where an m.1555G>A mutation has been identified

The decision to offer NAC to patients on nebulised aminoglycoside should be discussed and agreed by the CF MDT.

Dosing and administration guidance for patients requiring NAC during nebulised aminoglycoside therapy is the same as that for IV therapy.

  1. Kranzer et al; “A systematic review and meta-analysis of the efficacy and safety of N-acetylcysteine in preventing aminoglycoside-induced ototoxicity: implications for the treatment of multi-drug resistant TB”; Thorax, accessed via; first published 7th September 2015
  2. Clinical Guidelines: Care of Children with cystic fibrosis, 2020; Chapter 11, Drug Formulary; Royal Brompton and Harefield Hospitals, NHS; acceded via October 2021
Editorial Information

Last reviewed: 09 February 2022

Next review: 01 December 2024

Author(s): Susan Kafka, Dr Jane Wilkinson

Version: 1

Approved By: Paediatric Drugs & Therapeutics Committee

Document Id: 1007