Volume 199 - Issue 5
Fatal misuse of codeine–ibuprofen analgesics in Victoria, Australia
Authors: Jennifer L Pilgrim, Malcolm Dobbin and Olaf H Drummer
Med J Aust 2013; 199 (5): 329-331. || doi: 10.5694/mja12.11843
Published online: 2 September 2013
Published online: 2 September 2013
In Victoria, from 2001 to 2011, 115 deaths were identified with codeine and ibuprofen co-detected in postmortem toxicological analysis or with codeine-ibuprofen analgesic misuse described in the coroners’ findings.
To the Editor: Morbidity and mortality in cases where codeine from over-the-counter (OTC) combination analgesics is detected are usually secondary to codeine addiction and are the result of exposure to supratherapeutic doses of simple analgesics containing codeine. Toxicity from the accompanying analgesic, such as paracetamol, ibuprofen or aspirin, can lead to paracetamol hepatotoxicity, or non-steroidal anti-inflammatory drug (NSAID) toxicity such as gastrointestinal ulcers and haemorrhage,1 or renal tubular acidosis.2
In light of the increasing clinical evidence of codeine–ibuprofen analgesic misuse-related morbidity,3 we conducted a search for relevant cases from the National Coronial Information System, for individuals deceased in Victoria between 1 January 2001 and 31 December 2011. Ethics approval from the Victorian Department of Justice was obtained for the study. We included cases where codeine and ibuprofen were co-detected in postmortem toxicological analysis, or where codeine–ibuprofen analgesic misuse was described in the coroners’ findings. There were 115 such cases, comprising deaths from all causes, including deaths from natural disease (33 individuals), external injury (10), drug toxicity, not necessarily caused by the codeine-combination analgesics (63) and where the cause remained undetermined (nine).
Pathology reports and coroners’ findings in the cases flagged by a death investigator as potentially attributable to drug toxicity were examined more closely to identify any evidence of NSAID toxicity. Pathological examination findings typical of chronic NSAID toxicity were reported in seven individuals (who had both codeine and ibuprofen detected on postmortem toxicological analysis), manifesting as gastric erosions and ulceration in three individuals, chronic gastritis in one, renal necrosis and disease in two and hepatocyte necrosis in one. Of these, the cause of death was recorded as undetermined in one individual, natural disease in three, and drug toxicity involving an excess of codeine plus other drugs (including moclobemide, paracetamol and oxycodone) in a further three. Additionally, in one of these, the concentration of ibuprofen was also considered to be excessive.
There were two cases where codeine was detected without ibuprofen on postmortem toxicological analysis, but the death involved pathological findings indicative of chronic NSAID toxicity. One was attributed to a perforated gastric ulcer with peritonitis secondary to long-term misuse of Nurofen Plus (containing ibuprofen and codeine) (Reckitt Benckiser), which is the strongest codeine tablet available in Australia without prescription. A second case was attributed to codeine toxicity involving ibuprofen and benzodiazepines. This individual was a “doctor shopper” who was subject to a regimen that limited her access to one doctor and dispensing pharmacy. However, she was still able to obtain OTC medication.
Reports of misuse from OTC codeine-combination analgesics are increasing.4 Considering the risks of these drugs, we recommend that codeine not be included in these products, or that these products be confined to prescription-only.
Competing interests
No relevant disclosures.
References
- Dutch MJ. Nurofen Plus misuse: an emerging cause of perforated gastric ulcer. Med J Aust 2008; 188: 56-57. 0_BABJIEIH
- Ng JL, Morgan DJ, Loh NK, et al. Life-threatening hypokalaemia associated with ibuprofen-induced renal tubular acidosis. Med J Aust 2011; 194: 313-316. 0_i1142871
- Frei MY, Nielsen S, Dobbin MD, Tobin CL. Serious morbidity associated with misuse of over-the-counter codeine-ibuprofen analgesics: a series of 27 cases. Med J Aust 2010; 193: 294-296. 0_i1142873
- Nielsen S, Tobin C, Dobbin M. OTC codeine: examining the evidence for and against. Aust Pharm 2012; 31: 236-240. 0_i1142876