Tetrazepam[2] (is marketed under the following brand names,Clinoxan,Epsipam,Myolastan,Musaril,Relaxam andSpasmorelax) is abenzodiazepine derivative withanticonvulsant,anxiolytic,muscle relaxant and slightlyhypnotic properties. It was formerly used mainly in Austria, France, Belgium, Germany and Spain to treat muscle spasm, anxiety disorders such aspanic attacks, or more rarely to treatdepression,premenstrual syndrome oragoraphobia. Tetrazepam has relatively littlesedative effect at low doses while still producing useful muscle relaxation and anxiety relief. The Co-ordination Group for Mutual Recognition and Decentralised Procedures-Human (CMD(h)) endorsed the Pharmacovigilance Risk Assessment Committee (PRAC) recommendation to suspend the marketing authorisations of tetrazepam-containing medicines across the European Union (EU) in April 2013.[3] The European Commission has confirmed the suspension of the marketing authorisations for Tetrazepam in Europe because of cutaneous toxicity, effective from the 1 August 2013.[4]
The indicated adult dose for muscle spasm is 25 mg to 150 mg per day, increased if necessary to amaximum of 300 mg per day, individed doses. Tetrazepam is not generally recommended for use in children, except on the advice of a specialist.
Tetrazepam is only available in one strength and formulation, 50 mgtablets. Thebenzodiazepine equivalent of tetrazepam isapproximately 100 mg of tetrazepam = 10 mg ofdiazepam.[8]
Allergic reactions to tetrazepam occasionally occur involving the skin.[5]
Allergic reactions can develop to tetrazepam[9][10] and it is considered to be a potential allergen.[11][12] Drug rash and drug-inducedeosinophilia with systemic symptoms is a known complication of tetrazepam exposure.[13][14] These hypersensitive allergic reactions can be of thedelayed type.[15][16][17]
Patch testing has been used successfully to demonstrate tetrazepam allergy.[33][34] Oral testing can also be used. Skin prick tests are not always accurate and may produce false negatives.[35]
Drowsiness is a common side effect of tetrazepam.[36] A reduction in muscle force can occur.[37]Myasthenia gravis, a condition characterised by severe muscle weakness is another potential adverse effect from tetrazepam.[38] Cardiovascular and respiratory adverse effects can occur with tetrazepam similar to other benzodiazepines.[27]
Tetrazepam, like other benzodiazepines is a drug which is very frequently present in cases of overdose. These overdoses are often mixed overdoses, i.e. a mixture of other benzodiazepines or other drug classes with tetrazepam.[39][40]
Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children, alcohol or drug-dependent individuals and individuals withcomorbidpsychiatric disorders.[41]
Tetrazepam is an unusual benzodiazepine in its molecular structure as it has cyclohexenyl group which has substituted the typical 5-phenyl moiety seen in other benzodiazepines.[42]Tetrazepam, is rapidly absorbed after oral administration, within 45 mins and reaches peak plasma levels in less than 2 hours. It is classed as an intermediate acting benzodiazepine with an elimination half-life of approximately 15 hours. It is primarily metabolised to the inactive metabolites 3-hydroxy-tetrazepam andnortetrazepam.[42][43] The pharmacological effects of tetrazepam are significantly less potent when compared againstdiazepam, in animal studies.[44] Tetrazepam is a benzodiazepine site agonist and binds unselectively to type 1 and type 2 benzodiazepine site types as well as toperipheral benzodiazepine receptors.[45] The muscle relaxant properties of tetrazepam are most likely due to a reduction of calcium influx.[46] Small amounts ofdiazepam as well as theactive metabolites of diazepam are produced from metabolism of tetrazepam.[47][48] The metabolism of tetrazepam has led to false accusations of prisoners prescribed tetrazepam of taking illicit diazepam; this can lead to increased prison sentences for prisoners.[42]
Tetrazepam as with other benzodiazepines is sometimes abused. It is sometimes abused to incapacitate a victim in order to carry out a drug-facilitated crime.[49] or abused in order to achieve a state of intoxication.[50]Tetrazepam's abuse for to carry out drug facilitated crimes may be less however, than other benzodiazepines due to its reducedhypnotic properties.[51]
^Simiand J, Keane PE, Biziere K, Soubrie P (January 1989). "Comparative study in mice of tetrazepam and other centrally active skeletal muscle relaxants".Archives Internationales de Pharmacodynamie et de Therapie.297:272–85.PMID2567153.
^Perez-Guerrero C, Herrera MD, Marhuenda E (November 1996). "Relaxant effect of tetrazepam on rat uterine smooth muscle: role of calcium movement".The Journal of Pharmacy and Pharmacology.48 (11):1169–73.doi:10.1111/j.2042-7158.1996.tb03915.x.PMID8961167.S2CID38144317.
^Dinić-Uzurov V, Lalosević V, Milosević I, Urosević I, Lalosević D, Popović S (November 2007). "[Current differential diagnosis of hypereosinophilic syndrome]".Medicinski Pregled.60 (11–12):581–6.doi:10.2298/MPNS0712581D.PMID18666600.
^Bachmeyer C, Assier H, Roujeau JC, Blum L (July 2008). "Probable drug rash with eosinophilia and systemic symptoms syndrome related to tetrazepam".Journal of the European Academy of Dermatology and Venereology.22 (7):887–9.doi:10.1111/j.1468-3083.2007.02490.x.PMID18031497.S2CID12775035.
^Kämpgen E, Bürger T, Bröcker EB, Klein CE (November 1995). "Cross-reactive type IV hypersensitivity reactions to benzodiazepines revealed by patch testing".Contact Dermatitis.33 (5):356–7.doi:10.1111/j.1600-0536.1995.tb02060.x.PMID8565501.S2CID23398517.
^Sánchez I, García-Abujeta JL, Fernández L, Rodríguez F, Quiñones D, Duque S, et al. (2 March 1998)."Stevens-Johnson syndrome from tetrazepam".Allergologia et Immunopathologia.26 (2):55–7.PMID9645262. Archived fromthe original on 25 November 2020. Retrieved14 September 2009.
^Rodríguez Vázquez M, Ortiz de Frutos J, del Río Reyes R, Iglesias Díez L (September 2000). "[Erythema multiforme by tetrazepam]".Medicina Clinica.115 (9): 359.doi:10.1016/s0025-7753(00)71559-4.PMID11093904.
^Ghislain PD, Roussel S, Bouffioux B, Delescluse J (December 2000). "[Tetrazepam (Myolastan)-induced exanthema: positive patch tests in 2 cases]".Annales de Dermatologie et de Vénéréologie.127 (12):1094–6.PMID11173688.
^Breuer K, Worm M, Skudlik C, Schröder C, John SM (October 2009). "Occupational airborne contact allergy to tetrazepam in a geriatric nurse".Journal of the German Society of Dermatology.7 (10):896–8.doi:10.1111/j.1610-0387.2009.07096.x.PMID19453384.S2CID29339528.
^Barbaud A, Girault PY, Schmutz JL, Weber-Muller F, Trechot P (July 2009). "No cross-reactions between tetrazepam and other benzodiazepines: a possible chemical explanation".Contact Dermatitis.61 (1):53–6.doi:10.1111/j.1600-0536.2009.01558.x.PMID19659970.S2CID205813960.
^abcCabrerizo Ballesteros S, Méndez Alcalde JD, Sánchez Alonso A (2007)."Erythema multiforme to tetrazepam"(PDF).Journal of Investigational Allergology & Clinical Immunology.17 (3):205–6.PMID17583114.
^Schwedler S, Mempel M, Schmidt T, Abeck D, Ring J (1998). "Phototoxicity to tetrazepam - A new adverse reaction".Dermatology.197 (2):193–4.PMID9840980.
^Ferran M, Giménez-Arnau A, Luque S, Berenguer N, Iglesias M, Pujol RM (March 2005). "Occupational airborne contact dermatitis from sporadic exposure to tetrazepam during machine maintenance".Contact Dermatitis.52 (3):173–4.doi:10.1111/j.0105-1873.2005.0548o.x.PMID15811045.S2CID30499424.
^Barbaud A, Trechot P, Reichert-Penetrat S, Granel F, Schmutz JL (April 2001). "The usefulness of patch testing on the previously most severely affected site in a cutaneous adverse drug reaction to tetrazepam".Contact Dermatitis.44 (4):259–60.doi:10.1034/j.1600-0536.2001.440409-15.x.PMID11336014.S2CID40786622.
^Sánchez-Morillas L, Laguna-Martínez JJ, Reaño-Martos M, Rojo-Andrés E, Ubeda PG (2008)."Systemic dermatitis due to tetrazepam"(PDF).Journal of Investigational Allergology & Clinical Immunology.18 (5):404–6.PMID18973107.
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^Pérez-Guerrero C, Suárez J, Herrera MD, Marhuenda E (May 1997). "Spasmolytic effects of tetrazepam on rat duodenum and guinea-pig ileum".Pharmacological Research.35 (5):493–7.doi:10.1006/phrs.1997.0173.PMID9299217.
^Baumann A, Lohmann W, Schubert B, Oberacher H, Karst U (April 2009). "Metabolic studies of tetrazepam based on electrochemical simulation in comparison to in vivo and in vitro methods".Journal of Chromatography A.1216 (15):3192–8.doi:10.1016/j.chroma.2009.02.001.PMID19233363.
^Schubert B, Pavlic M, Libiseller K, Oberacher H (December 2008). "Unraveling the metabolic transformation of tetrazepam to diazepam with mass spectrometric methods".Analytical and Bioanalytical Chemistry.392 (7–8):1299–308.doi:10.1007/s00216-008-2447-4.PMID18949465.S2CID10967477.
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