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What is Metapain®?

Metapain® is a fixed dose oral combination of 30 mg nefopam & 500 mg paracetamol. Centrally acting non-opioid analgesics, paracetamol and nefopam have different mechanisms of action.

A combination
of two analgesics


Nefopam is a non-opioid analgesic drug used to treat postoperative pain. Nefopam inhibits the reuptake of catecholamines (noradrenaline, dopamine) and serotonin and acts on glutamatergic transmission via the modulation of calcium and sodium ion channels which leads to a decrease in the activation of glutamatergic NMDA receptors.


Paracetamol is one of the most popular analgesics used daily worldwide to relieve light-to-moderate pain, but its hepatotoxicity is a major limitation.  Paracetamol would behave as a pro-drug whose active metabolite (AM404) ensures the central analgesic action, at the level of the peri-aqueductal gray matter, with secondarily activation serotoninergic bulbospinal pathways inhibiting the transmission of the pain message.

Metapain® indication: acute pain which can’t easily be treated by paracetamol alone, opioids or NSAID because of side effects or counter-indication (to avoid the risk of opioid abuses)

Pain definition-Définition de la douleur, aptys Pharma, laboratoire pharmaceutique, clermont-Ferrand, france

Metapain® ?

Metapain® has been developed to fill the gap in the arsenal of pain treatment due to the withdrawal of dextropropoxyphene (Di-Antalvic®, Propofan®) which left no non-opioid, non-NSAID alternative.

Pain affects about 20% of the world’s population. This high prevalence is the result of population ageing, increase of chronic diseases (diabetes, obesity) and change of behavior of patients and physicians to pain. The State of Innovation in Highly Prevalent Chronic Diseases, February 2018, Pain in Europe – a public health priority, September 2011

Recent scandals and revelations around the opioids abuse market resulted in an urgent need for opioid-free alternatives. https://www.cdc.gov/opioids/data/analysis-resources.html

a real impact

  • The opioid crisis is now hitting the whole world and caused more than 100,000 deaths recorded in the United States in the 12-month period ending in April 2022 (General Surgery News, May 5, 2022).
  • The global pain market was $71.4 billion in 2019 with an average annual growth rate of 3.8%, a prospect of $91.6 billion in 2027 (Dun & Bradtstreet Sept 2020).
  • The overall impact of pain in the USA (treatments, care, work stoppages, etc.) is estimated at $635 billion in 2017 (The State of Innovation in Highly Prevalent Chronic Diseases, February 2018).
  • Impact of pain on society costs the EU up to 441 billion Euros annually (Press information SIP 2017).

What are the
advantages of Metapain®?

  • Single components co-prescribed in Europe
  • Multimodal effect1,2,3,4
  • Synergistic / additive effect5,6,7,8
  • Well tolerated
  • Reduction of hepatotoxicity
  • Patents protected


  • Clinical proof of concept in moderate to severe pain.
  • First patent granted in 21 countries (PCT/EP2020/050660, WO 2020/148217)
  • Second patent filed in 2023 (PCT/IB2023/055059)
  1. PCT/EP2020/050660, WO 2020/148217, PCT/IB2023/055059
  2. Jin, F. and Chung, F., Journal of Clinical Anesthesia. 2001, Vol. 13, pp. 524-39.
  3. Girard, P., et al., Clinical and Experimental Pharmacology and Physiology. 2016, Vol. 43, pp. 3-12
  4. Faruqui, A.A, et al, Ann Anesth Pain Med. 2020; 3 (1): 1016.
  5. Girard, P. et al, Clinical and Experimental Pharmacology and Physiology. 2011, Vol. 38, pp. 170-8.
  6. Cabañero, D. and Maldonado, R., Eur J Pain. 2021; 25:1770–1787. 2021
  7. Van Elstraete, A.C. and Sitbon, P.,  Minerva Anestesiologica. 2013, Vol. 79(4), pp. 1-8
  8. Delage N. et al, Anesthesiology. 2005 Jun;102(6):1211-6.
Metapain-Etude-phase 3

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