Manufacturers report that tolperisone should not be used in patients with myasthenia gravis. Only limited data are available regarding the safety in children, youths, during pregnancy and breastfeeding. It is not known whether tolperisone is excreted into mother's milk.[3][4]
In 2012, following concerns about safety and efficacy, an "article 31 referral"[5] was triggered at the European Medicines Agency (EMA). After the review and a subsequent re-examination, the Agency concluded that the benefits of tolperisone-containing medicines given orally continue to outweigh their risks. However, there is weak support for tolperisone's efficacy, specifically due to the prevalence of hypersensitivity symptoms such as flushing, rash, severe skin itchiness (with raised lumps), wheezing, difficulty breathing and swallowing, fast heartbeat, and fast decrease in blood pressure (basically anaphylaxis). The EMA recommends that tolperisone use be restricted to the treatment of adults with post-stroke spasticity (stiffness). The EMA also advises cessation of advertising, only using tolperisone orally, updating patient information leaflets, and changing to another medicine for existing users.[6]
Adverse effects occur in fewer than 1% of patients and include muscle weakness, headache, arterial hypotension, nausea, vomiting, dyspepsia, and dry mouth. All effects are reversible.[3][4] Allergic reactions occur in fewer than 0.1% of patient and include skin rash, hives, Quincke's edema, and in some cases anaphylactic shock.[3][7][8][9]
Excitability has been noted after ingestion of high doses by children.[3] In suicide studies of three isolated cases, it is believed that ingestion of tolperisone was the cause of death.[10]
Tolperisone does not have a significant potential for interactions with other pharmaceutical drugs. It cannot be excluded that combination with other centrally acting muscle relaxants, benzodiazepinesornonsteroidal anti-inflammatory drugs (NSAIDs) may make a dose reduction necessary in some patients.[3][4]
Tolperisone is absorbed nearly completely from the gut and reaches its peak blood plasma concentration after 1.5 hours. It is extensively metabolised in the liver and kidneys. The substance is excreted via the kidneys in two phases; the first with a half-life of two hours, and the second with a half-life of 12 hours.[3]
^Kwaśniewski A, Korbuszewska-Gontarz B, Mika S (2003). "[Mydocalm causing anaphylaxis]". Pneumonologia I Alergologia Polska (in Polish). 71 (5–6): 250–252. PMID14587432.
^Glück J, Rymarczyk B, Rogala B (2011). "An immediate hypersensitivity reaction caused by tolperisone hydrochloride". Journal of Investigational Allergology & Clinical Immunology. 21 (5): 411–412. PMID21905508.
^Sporkert F, Brunel C, Augsburger MP, Mangin P (February 2012). "Fatal tolperisone poisoning: autopsy and toxicology findings in three suicide cases". Forensic Science International. 215 (1–3): 101–104. doi:10.1016/j.forsciint.2011.05.025. PMID21683537.
^Kocsis P, Farkas S, Fodor L, Bielik N, Thán M, Kolok S, et al. (December 2005). "Tolperisone-type drugs inhibit spinal reflexes via blockade of voltage-gated sodium and calcium channels". The Journal of Pharmacology and Experimental Therapeutics. 315 (3): 1237–1246. doi:10.1124/jpet.105.089805. PMID16126840. S2CID13020517.
^Hofer D, Lohberger B, Steinecker B, Schmidt K, Quasthoff S, Schreibmayer W (May 2006). "A comparative study of the action of tolperisone on seven different voltage dependent sodium channel isoforms". European Journal of Pharmacology. 538 (1–3): 5–14. doi:10.1016/j.ejphar.2006.03.034. PMID16650844.
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