Guidance for the use of Acetylcysteine in patients
with Pulmonary Fibrosis
Acetylcysteine is unlicensed in the UK and any doctor who prescribes the medication legally assumes
clinical responsibility for the drug, and the consequences of its use.
Introduction:
Acetylcysteine is a precursor of glutathione, an antioxidant, and so prevents cellular damage. It is
thought to inhibit glutathione depletion and thus reduce fibroproliferation1.
Acetylcysteine has been shown to delay the decline in lung function in patients with idiopathic
Pulmonary Fibrosis. Its use (Acetylcysteine 600 mg three times daily) added to Prednisone
and Azathioprine, showed preservation of vital capacity and carbon monoxide diffusing capacity
better than did Azathioprine and Prednisolone alone2.
Use of this combination (Acetylcysteine, Prednisolone and Azathioprine) has now been discontinued
due to poorer patient outcomes in clinical trials by the National Heart, Lung and Blood Institute. As a
result, the British Thoracic Society3 (BTS) has recommended against its use. Monotherapy with
Acetylcysteine remains safe in idiopathic Pulmonary Fibrosis and the BTS recommends its use.
With respect to a definite diagnosis for idiopathic Pulmonary Fibrosis, the BTS recommends3:


Patients with definite, newly diagnosed idiopathic Pulmonary Fibrosis should not be initiated
on a regimen containing Prednisolone plus Azathioprine
Patients currently receiving ‘triple’ therapy and who experience disease progression (declining
lung function), should have Azathioprine, in particular, withdrawn.
Patients established on ‘triple’ therapy who do not experience disease progression (i.e.
‘stable’ disease) should be discussed on an individual basis with respect to continuation of
therapy. The decision to withdraw should be on a case by case basis but the threshold for
withdrawing azathioprine from elderly patients should be low.
Contraindications4,5:
 Hypersensitivity to Acetylcysteine (or any of the other ingredients in the tablet) including
bronchospasm, rash, pruritus, angioedema, flushing, nausea, vomiting; this list is not
exhaustive and is more common with the intravenous use of Acetylcysteine.
 Children under the age of 14 years (high dose oral Acetylcysteine).
 First presentation of severe skin and mucous membrane reactions. Very rare incidences of
Stevens-Johnson syndrome and Lyell’s syndrome have been reported.
 Active Gastrointestinal ulceration.
Use with caution in the presence of any of the following4,5:
 Bronchial asthma- risk of bronchospasm and exacerbation of asthma, however, this is most
common with the intravenous formulation.
 Previous stomach or intestinal ulceration- drug-induced nausea and vomiting may lead to GI
haemorrhage in this patient group. Mucolytics may disrupt the mucosal barrier.
 Hepatic impairment- leads to reduced clearance.
 Histamine intolerance (symptoms leading to headaches, runny nose, itching) - avoid long term
use.
BHNFT October 2013
Drug interactions5
Antitussives
The combined action of a reduced cough reflex with antitussives and the use of acetylcysteine can
lead to a dangerous build-up of mucus secretions. Advise patients on the use of over the counter
preparations.
Antibiotics
Acetylcysteine may reduce the efficacy of certain antibiotics (particularly; tetracycline’s,
aminoglycosides, and penicillin’s). Allow a 2 hour gap between Acetylcysteine and these antibiotics to
prevent the interaction.
Dosage, administration and treatment duration:
Treatment with Acetylcysteine will be initiated by a specialist. The dosing schedule is as follows:
Acetylcysteine effervescent tablets
600mg TDS
The patient should be advised to take the
tablets by dissolving them in one glass of
water or by swallowing them whole with
plenty of water. They should be taken
after meals.
Treatment will be reviewed periodically by the initiating specialist and therapy should be continued
with the instruction of the specialist.
Excipients:
BHNFT currently uses ACC 600mg brand tablets, made by Hexal (imported from Germany). The
inactive ingredients in the tablets are microcrystalline stearate, maize starch, sodium cyclamate,
sodium saccharin and flavourings (lemon).
Monitoring:
The only monitoring routinely required whilst on Acetylcysteine is respiratory function and evidence of
adverse effects.
Liver and renal function need only be monitored if the patient has pre-existing dysfunction.
Adverse effects:
The most common side effects of treatment include; headache, fever, allergic reactions (breathing
difficulties, rash, pruritus, tachycardia, hypotension), nausea, vomiting, diarrhoea, abdominal pain and
inflammation of mucous membranes in the mouth. Worsening of these symptoms should warrant
medical attention and withdrawal from therapy.
Rarely bronchospasm, mostly in asthmatic patients, may occur.
Very rarely anaphylactic reactions and shock may occur. Hypersensitivity reactions, with bleeding,
may very infrequently occur, at which point therapy should be stopped.
Pregnancy and Lactation:
Due to insufficient knowledge of use, Acetylcysteine is contraindicated during pregnancy and
lactation.
Immediate advice and support
Contact Details
Medicines Information BHNFT
Dr H A Mahdi
Dr M J Malik
Telephone No
01226 432857
01226 730000
01226 730000
Fax No
01226 434431
Email
Gilliansmith2@nhs.net
References:
1.
2.
3.
4.
5.
Oral N-acetylcysteine for Idiopathic Pulmonary Fibrosis: unlicensed and off-label medicines report number 4 (2011), Wessex Drug
and Medicines Information Centre, UK Medicines Information, pp. 1-10 (accessed from www.nelm.nhs.uk)
Demedts, M. et. al (2005) High Dose Acetylcysteine in Idiopathic Pulmonary Fibrosis, The New England Journal of Medicine;353:pp
2229-42
British Thoracic Society. Accessed online ( 03/10/2013) http://www.brit-thoracic.org.uk/Guidelines/Interstitial-Lung-Disease-DPLDGuideline.aspx
Martindale. Accessed online (04/10/2013) www.medicinescomplete.com
ACC 600mg tablets- Patient information leaflet (translated in to English by Durbin Plc.)
BHNFT October 2013