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Hydroxyzine Embonate (BANM, Rinnm) 1

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Hydroxyzine Embonate (BANM, Rinnm) 1 Flunarizine Hydrocohloride/Hydroxyzine 581 cellular hypoxia, and improved blood viscosity and erythrocyte Profile Adverse Effects and Precautions deformability. Calcium-channel blocking activity might have a Homochlorcyclizine hydrochloride, a piperazine derivative, is a As for the sedating antihistamines in general, p.561. role, but evidence for the efficacy of other calcium-channel sedating antihistamine (p.561) with antimuscarinic and moderate blockers in migraine prophylaxis (see Nifedipine, p.1355) is less sedative properties. It is used for the symptomatic relief of aller- Intramuscular injection of hydroxyzine has been re- convincing than for flunarizine. gic conditions including urticaria (p.565) and rhinitis (p.565), ported to cause marked local discomfort. Intravenous Case reports have indicated benefit with flunarizine in the proph- and in pruritic skin disorders (p.565). It is given in oral doses of use has been associated with haemolysis. 10 to 20 mg three times daily. ylaxis of the rare disorder of alternating hemiplegia in Amputation. Accidental intra-arterial injection of hydroxyzine childhood5,6 but a subsequent study7 in 12 children did not pro- 8 Preparations has led to necrosis of the extremity requiring amputation of the duce conclusive findings. A later long-term study reported that 1 Proprietary Preparations (details are given in Part 3) digits of the affected limb. 7 of 9 children given flunarizine for up to 5 years for hemiplegia 1. Hardesty WH. Inadvertent intra-arterial injection. JAMA 1970; Hong Kong: Homoclomin; Indon.: Homoclomin; Jpn: Homoclomin; showed a reduction in the duration of attacks, and 3 had a reduc- 213: 872. tion in frequency, but only 1 of these obtained a complete cessa- Thai.: Homoclomin. tion of episodes. Arrhythmias. ECG abnormalities, particularly alterations in T- waves, were associated with anxiolytic doses of hydroxyzine hy- The role of antihistamines in general in the management of mi- drochloride and were similar to those produced by thioridazine graine is discussed briefly on p.564. 1 Hydroxyzine (BAN, rINN) and tricyclic antidepressants. 1. Todd PA, Benfield P. Flunarizine: a reappraisal of its pharmaco- 1. Hollister LE. Hydroxyzine hydrochloride: possible adverse car- logical properties and therapeutic use in neurological disorders. diac interactions. Psychopharmacol Comm 1975; 1: 61–5. Drugs 1989; 38: 481–99. Hidroxizina; Hydroksitsiini; Hydroxizin; Hydroxyzinum. (RS)-2-{2- 2. Andersson K-E, Vinge E. β-Adrenoceptor blockers and calcium [4-(p-Chloro-α-phenylbenzyl)piperazin-1-yl]ethoxy}ethanol. Effects on sexual function. A 32-year-old man had prolonged penile erections (priapism) after taking two separate doses of hy- antagonists in the prophylaxis and treatment of migraine. Drugs Гидроксизин 1990; 3: 355–73. droxyzine for a skin rash.1 It was suggested that the effect might 3. Soelberg Sørensen P, et al. Flunarizine versus metoprolol in mi- C21H27ClN2O2 = 374.9. be due to a hydroxyzine metabolite that was found to be structur- graine prophylaxis: a double-blind, randomized parallel group CAS — 68-88-2. ally similar to a metabolite of trazodone, a drug known to induce study of efficacy and tolerability. Headache 1991; 31: 650–7. penile erections. ATC — N05BB01. 4. Gawel MJ, et al. Comparison of the efficacy and safety of fluna- 1. Thavundayil JX. et al. Prolonged penile erections induced by hy- rizine to propranolol in the prophylaxis of migraine. Can J Neu- ATC Vet — QN05BB01. droxyzine: possible mechanism of action. Neuropsychobiology rol Sci 1992; 19: 340–5. 1994; 30: 4–6. 5. Casaer P, Azou M. Flunarizine in alternating hemiplegia in child- hood. Lancet 1984; ii: 579. Effects on the skin. Four children given hydroxyzine hydro- 6. Curatolo P, Cusmai R. Drugs for alternating hemiplegic mi- Cl O chloride for restlessness developed a fixed drug eruption of the graine. Lancet 1984; ii: 980. N OH penis.1 All recovered on drug withdrawal and subsequently had 7. Casaer P. Flunarizine in alternating hemiplegia in childhood. An positive rechallenges. international study in 12 children. Neuropediatrics 1987; 18: N 1. Cohen HA, et al. Fixed drug eruption of the penis due to hydrox- 191–5. yzine hydrochloride. Ann Pharmacother 1997; 31: 327–9. 8. Silver K, Andermann F. Alternating hemiplegia of childhood: a 1 study of 10 patients and results of flunarizine treatment. Neurol- Liver disorders. A study has suggested that hydroxyzine ogy 1993; 43: 36–41. should only be given once daily for the relief of pruritus in pa- 1 tients with primary biliary cirrhosis. The mean serum elimination Tourette’s syndrome. A small unblinded study involving 7 half-lives of hydroxyzine and its metabolite cetirizine in 8 pa- patients has suggested that flunarizine is more effective than pla- tients with primary biliary cirrhosis were 36.6 and 25.0 hours re- cebo in the treatment of Tourette’s syndrome (see Tics, p.954). spectively. 1. Micheli F, et al. Treatment of Tourette’s syndrome with calcium Hydroxyzine Embonate (BANM, rINNM) 1. Simons FER, et al. The pharmacokinetics and pharmacodynam- antagonists. Clin Neuropharmacol 1990; 13: 77–83. ics of hydroxyzine in patients with primary biliary cirrhosis. J Embonato de hidroxizina; Hydroxyzine, Embonate d’; Hydrox- Clin Pharmacol 1989; 29: 809–15. Vertigo. Antihistamines are the mainstay of the treatment of yzine Pamoate; Hydroxyzini Embonas; Pamoato de hidroxizina. vertigo (p.565). However, their antimuscarinic adverse effects Porphyria. Hydroxyzine has been associated with acute attacks may prove troublesome, particularly in the elderly, and they pro- 2-{2-[4-(4-Chlorobenzhydryl)piperazin-1-yl]ethoxy}ethanol of porphyria and is considered unsafe in porphyric patients. duce central sedation. Flunarizine is devoid of antimuscarinic 4,4′-methylenebis(3-hydroxy-2-naphthoate). properties, although it may produce central sedation. Гидроксизина Эмбонат Interactions Preparations C21H27ClN2O2,C23H16O6 = 763.3. As for the sedating antihistamines in general, p.563. Proprietary Preparations (details are given in Part 3) CAS — 10246-75-0. Arg.: Bercetina; Coromert; Flufenal; Mondus; Niflucan; Sibelium; Vascu- ATC — N05BB01. Pharmacokinetics loflex†; Austria: Amalium; Flunarium; Sibelium; Belg.: Flunarimed; Fluna- ATC Vet — QN05BB01. Hydroxyzine is rapidly absorbed from the gastrointes- top; Kelamigra; Sibelium; Braz.: Flunarin; Fluvert; Fluzix; Sibelium; Vertigium; Ver tix; Canad.: Sibelium; Chile: Flerox; Fluxus; Irrigor; Sibelium; Zentralin; Pharmacopoeias. In Jpn and US. tinal tract and is metabolised. Metabolites include ceti- Cz.: Sibelium; Denm.: Sibelium; Fr.: Sibelium; Ger.: Flunavert; Natil-N; Si- USP 31 (Hydroxyzine Pamoate). A light yellow, practically rizine (p.570), which has antihistaminic activity. An belium; Gr.: Sibelium; Hong Kong: Fludan; Sibelium†; Hung.: Sibelium; In- dia: Migarid; Nomigrain; Indon.: Bartolium; Cevadil; Degrium; Dizilium; odourless powder. Soluble 1 in more than 1000 of water, of chlo- elimination half-life of about 20 hours has been report- Frego; Sibelium; Siberid; Silum; Sinral; Unalium; Xepalium; Irl.: Sibelium; roform, and of ether, 1 in 700 of alcohol, 1 in 10 of dimethylfor- ed. Ital.: Flugeral; Flunagen; Fluxarten; Gradient; Issium; Sibelium; Vasculene; mamide, and 1 in 3.5 of 10M sodium hydroxide solution; practi- Malaysia: Fludan; Forknow; Migarid; Sibelium; Mex.: Axilin; Fasolan; cally insoluble in methyl alcohol. Store in airtight containers. ◊ References. Nafluryl; Sibelium; Neth.: Sibelium; Philipp.: Sibelium; Port.: Sibelium; Va- 1. Paton DM, Webster DR. Clinical pharmacokinetics of H -recep- silium; Zinasen; S.Afr.: Sibelium; Singapore: Forknow; Narizine†; Sibel- tor antagonists (the antihistamines). Clin Pharmacokinet 1985; ium†; Spain: Flerudin; Flurpax; Sibelium; Switz.: Sibelium; Thai.: Cede- (BANM, rINNM) 10: 477–97. late†; Finelium†; Floxin; Fludan; Flulium; Flunarium; Flunaza†; Flunazine†; Hydroxyzine Hydrochloride Fluricin; Hexilium; Liberal; Medilium; Poli-Flunarin; Seabell†; Sibelium; Si- Hidrocloruro de hidroxizina; Hidroksizin Hidroklorür; Hidrok- Liver disorders. For reference to a prolonged half-life of hy- moyiam; Sobelin; Vanid; Vertilium; Zelium; Turk.: Sibelium; Venez.: Fludil; sizino hidrochloridas; Hidroxizin-hidroklorid; Hydroksitsiinihy- droxyzine in patients with primary biliary cirrhosis, see under Sibelium. Adverse Effects and Precautions, above. Multi-ingredient: Arg.: Angiolit†; CCK Flunarizina†; Sibelium Plus; Braz.: drokloridi; Hydroxizinhydroklorid; Hydroxyzin dihydrochlorid; Ver tizine D. Hydroxyzine, chlorhydrate d’; Hydroxyzini Dihydrochloridum; Hydroxyzini hydrochloridum. Uses and Administration Hydroxyzine, a piperazine derivative, is a sedating an- Гидроксизина Гидрохлорид tihistamine with antimuscarinic and significant seda- Homochlorcyclizine Hydrochloride (BANM, rINNM) C21H27ClN2O2,2HCl = 447.8. tive properties; it is also an antiemetic. Its main use is Hidrocloruro de homoclorciclizina; Homochlorcyclizine, Chlo- CAS — 2192-20-3. as an anxiolytic (p.952) but see Anxiety Disorders be- rhydrate d’; Homochlorcyclizini Hydrochloridum. 1-(4-Chlo- ATC — N05BB01. low. It is also used as an adjunct to pre- and postopera- robenzhydryl)perhydro-4-methyl-1,4-diazepine dihydrochloride. ATC Vet — QN05BB01. tive medication (see Anaesthesia, p.563) and in the Гомохлорциклизина Гидрохлорид Pharmacopoeias. In Eur. (see p.vii), Jpn, and US. management of pruritus (p.565) and urticaria (p.565) Ph. Eur. 6.2 (Hydroxyzine Hydrochloride). A white or almost C19H23ClN2,2HCl = 387.8. and has
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