http://orcid.org/0000-0003-2506-0301
Risk minimization measures (RMMs) were implemented to prevent or reduce the possibility of serious adverse reactions associated with exposure to a medicine, or to reduce their severity impact on the patient in the case of an adverse reactionCitation1. Flupirtine is a non-opioid, centrally acting analgesic that has N-methyl-D-aspartate (NMDA) receptor antagonizing propertiesCitation2. It belongs to a unique group of drugs known as selective neuronal potassium channel openers (SNEPCOs). It is not approved by US-FDA but has been approved for use in European countries with implementation of RMMsCitation3.
Flupirtine has been available for clinical use for several decades but has been less frequently used and even neglected in discussions on non-opioid analgesicsCitation4. Flupirtine has been used successfully in managing postoperative pain as it possesses morphine-sparing properties and also in treating chronic pain conditions when all other modalities have been unsuccessful. With RMM implementation, flupirtine has found a resurgence as detailed in a retrospective study by Kaplan et al. where short-term use of flupirtine increased by 22.7% in Germany, although the overall use decreased when compared to pre-RMM implementationCitation5.
Hepatotoxicity with the use of flupirtine is a cause of concern and therefore weekly liver function tests are advised if used for a duration of more than 2 weeks. Problems are more common when combination medications containing flupirtine are used that may have a more pronounced hepatotoxic effect. Other analgesics such as NSAIDs are notorious for contributing to life-threatening cardiovascular (myocardial infarction, stroke) or renal (renal failure) events but are still used and prescribed rampantlyCitation6.
On the other hand, flupirtine is a drug worth trying in patients in whom NSAIDs are contraindicated (advanced age, borderline serum creatinine levels) and in patients nonresponsive to routine opioid medications.
Moreover, there is potential for Germany to conduct well designed randomized controlled trials using flupirtine with other analgesics and/or placebo. If the results are encouraging and if short term safety is established in an RRM-implementing country, flupirtine can be considered by the US-FDA for regular use especially in the peri-operative period where use is short term.
In conclusion, RMMs have put a check on indiscriminate and unmonitored use of drugs such as flupirtine that can lead to adverse events. Data on safety of short term flupirtine under RMMs can be useful in modifying analgesic plans for postoperative periods in future.
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References
- Mazzaglia G, Straus SMJ, Arlett P, et al. Study design and evaluation of risk minimization measures: a review of studies submitted to the European medicines agency for cardiovascular, endocrinology, and metabolic drugs. Drug Saf. 2018;41:191–202.
- Harish S, Bhuvana K, Bengalorkar GM, et al. Flupirtine: clinical pharmacology. J Anaesthesiol Clin Pharmacol. 2012;28:172–177.
- European Medicines Agency: EMA/404308/2013. Assessment report for flupirtine containing medicinal products [Internet]. 2013 [cited 2017 Sep 24]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Flupirtine-containing_medicines/Recommendation_provided_by_Pharmacovigilance_Risk_Assessment_Committee/WC500146103.pdf
- Nair AS. Flupirtine: a less-explored, neglected nonopioid analgesic. Anesth Analg. 2018;126:1425.
- Kaplan S, Ehlken B, Hamann X. Drug utilization patterns of flupirtine following implementation of risk minimization measures in Germany. Curr Med Res Opin. [cited 2019 Mar 13]; [7 p.]. DOI:10.1080/03007995.2019.1594743
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