Published: 7 March 2019

Publications

Modified-release paracetamol – Unpredictable in overdose

Prescriber Update 40(1): 7–8
March 2019

Key Messages

  • Overdose of modified-release paracetamol medicines is difficult to treat due to prolonged absorption and unpredictable pharmacokinetics.
  • Contact the Poisons Centre for advice if overdose with modified-release paracetamol is suspected.
  • Modified-release paracetamol has been reclassified from Pharmacy Only to Restricted (Pharmacist Only) Medicine, in order for pharmacists to provide more information on dosing to patients.


The Medicines Adverse Reaction Committee (MARC) reviewed the safety of modified-release paracetamol at the 172nd meeting on 7 December 2017, following the suspension of these medicines in Europe1.

Modified-release paracetamol formulation

Modified-release paracetamol tablets are marketed in New Zealand in a formulation containing 665 mg of paracetamol, which is taken up to three times a day2–4.

The modified-release tablets contain both immediate-release paracetamol (31%) and slow-release paracetamol (69%).

Paracetamol overdose

Products formulated as modified-release paracetamol have acceptable quality, safety and efficacy when taken at the recommended dose.

Paracetamol overdose, whether intentional or accidental, has the potential to cause liver failure. Treatment with N-acetyl cysteine when given early enough can prevent these effects. However, when an overdose involves modified-release paracetamol treatment can be more difficult.

Overdose with modified-release paracetamol results in a prolonged and unpredictable pattern of paracetamol absorption. Serum paracetamol concentration may peak as late as 24 hours after ingestion of modified-release paracetamol. With very large overdoses, the modified-release tablets may form a clump (called a pharmacobezoar) in the gut, which can further delay absorption due to altered disintegration and dissolution properties of the clumped tablets5.

Standard treatment guidelines for overdose of immediate-release paracetamol are not designed for these extended periods of absorption. The slow absorption and unpredictable pharmacokinetics of modified-release paracetamol following overdose may lead to a delayed peak in serum paracetamol concentration above the nomogram line5. The MARC noted that the current paracetamol poisoning guidelines could be improved to deal with overdoses of modified-release paracetamol1.

In situations where an overdose involving modified-release paracetamol is suspected, call the National Poisons Centre on 0800 POISON (0800 764 766) for advice.

Modified-release paracetamol is now a Restricted (Pharmacist Only) Medicine

The Medicines Classification Committee (MCC) reviewed the classification of modified-release paracetamol at the 60th meeting in April 20186 and at the 61st meeting in November 20187. The MCC recommended that modified-release paracetamol should be reclassified from Pharmacy Only to Restricted (Pharmacist Only) Medicine. The reclassification notice was published in February 2019 (https://gazette.govt.nz/notice/id/2019-go841).

The Restricted Medicine classification maintains over-the-counter access to the medicine while ensuring that consumers receive information from a pharmacist about how to take the medicine correctly, and not taking other paracetamol-containing medicines at the same time.

References
  1. Medsafe. 2017. Minutes of the 172nd Medicines Adverse Reactions Committee Meeting 20 December 2017. URL: www.medsafe.govt.nz/profs/adverse/Minutes172.htm (accessed 5 February 2019).
  2. Chiew AL, Fountain JS, Graudins A, et al. 2015. Summary statement: New guidelines for the management of paracetamol poisoning in Australia and New Zealand. Medical Journal of Australia 203(5): 215–18. DOI: 10.5694/mja15.00614 (accessed 17 January 2019).
  3. Tan C, Graudins A. 2006. Comparative pharmacokinetics of Panadol Extend and immediate-release paracetamol in a simulated overdose model. Emergency Medicine Australasia 18(4): 398–403. DOI: 10.1111/j.1742-6723.2006.00873.x (accessed 17 January 2019).
  4. GlaxoSmithKline Consumer Healthcare. 2018. Panadol Osteo 665 mg modified-release tablets New Zealand Data Sheet 13 March 2018. URL: www.medsafe.govt.nz/profs/Datasheet/p/panadolOsteocaplets.pdf (accessed 17 January 2019).
  5. Salmonsen H, Sjöberg G, Brogren J. 2018. The standard treatment protocol for paracetamol poisoning may be inadequate following overdose with modified release formulation: a pharmacokinetic and clinical analysis of 53 cases. Clinical Toxicology 56(1): 63–8. DOI: 10.1080/15563650.2017.1339887 (accessed 17 January 2019).
  6. Medsafe. 2018. Minutes of the 60th meeting of the Medicines Classification Committee held in Wellington on 26 April 2018 at 9:30 am. URL: www.medsafe.govt.nz/profs/class/Minutes/2016-2020/mccMin26April2018.htm (accessed 17 January 2019).
  7. Medsafe. 2018. Minutes of the 61st meeting of the Medicines Classification Committee held in Wellington on 2 November 2018 at 9:30 am. URL: www.medsafe.govt.nz/profs/class/Minutes/2016-2020/mccMin2Nov2018.htm (accessed 17 January 2019).