Carbocisteine and acetylcysteine: Anaphylactic/anaphylactoid reactions and Severe Cutaneous Adverse Reactions (SCARs)


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Carbocisteine and acetylcysteine (also known as N-acetylcysteine or NAC) are cysteine derivatives indicated for use as mucolytic agents. They are assumed to reduce mucus viscosity by breaking the disulfide bonds, and thus promoting expectoration. In addition, acetylcysteine is well-established as a specific antidote in paracetamol overdose. Acetylcysteine is also commonly used off-label as a nephroprotective agent in prevention of radiocontrast-induced nephropathy.

In Malaysia, carbocisteine and acetylcysteine are registered as controlled medicines or over-the-counter medicines (OTC), available in either single-ingredient or combination products1. Given its antioxidant properties, acetylcysteine is also found in some health supplements.


Background of Safety Issue1,2,3,4,5

The National Pharmaceutical Regulatory Agency (NPRA) initiated a safety review on the potential risk of anaphylactic/anaphylactoid reactions and severe cutaneous adverse reactions (SCARs) with the use of carbocisteine. This safety review was triggered through the submission of new safety information by the product registration holder of carbocisteine. NPRA subsequently extended the review to include another cysteine derivative, acetylcysteine.

Based on the safety findings, it was suggested that both carbocisteine and acetylcysteine are associated with anaphylactic/anaphylactoid reactions. Further to the review, the occurrence of serious skin reactions such as erythema multiforme, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with the use of carbocisteine and acetylcysteine. In most of these reported cases of SCAR, at least one other drug was concurrently administered, which may have contributed to the described mucocutaneous effects.

Having considered the current available evidence from local and global post-marketing case reports, scientific literature, input of local clinical experts, as well as action taken by foreign regulatory authorities, NPRA concluded that an update of the labels and package inserts of carbocisteine- and acetylcysteine-containing products is warranted to reflect the possibly life-threatening risks discussed above.


Adverse Drug Reaction Reports2


Advice for Healthcare Professionals

Carbocisteine and Acetylcysteine (for indications other than paracetamol overdose)

Acetylcysteine for Paracetamol Overdose5,6


A directive [Ruj. Kami: (14) dlm. BPFK/PPP/07/25 Jld. 2] has been issued by NPRA for updates to the local product packaging insert and consumer medication information leaflet (Risalah Maklumat Ubat untuk Pengguna) related to this safety issue. Please refer to the directive for more information.



  1. The NPRA QUEST 3+ database, [Accessed: 16 November 2017]
  2. The Malaysian National ADR Database, NPRA [Accessed: 16 November 2017]
  3. The WHO VigiLyze Database, Uppsala Monitoring Centre (UMC) [Accessed: 27 November 2017]
  4. Yavuz H & Emiroglu M (2011). Toxic epidermal necrolysis treated with N-acetylcysteine. Pediatrics International, 56, e52–e54.
  5. Medicines & Healthcare Products Regulatory Agency (MHRA) (2012). Paracetamol overdose: Simplification of the use of intravenous acetylcysteine. Safety Warnings and Messages for Medicines. United Kingdom.
  6. Pharmaceutical Services Division (2015). Clinical Pharmacokinetics Pharmacy Handbook. Ministry of Health Malaysia.



This publication is aimed at health professionals. The information is meant to provide updates on medication safety issues, and not as a substitute for clinical judgement. While reasonable care has been taken to verify the accuracy of the information at the time of publication, the NPRA shall not be held liable for any loss whatsoever arising from the use of or reliance on this publication.