996 Anxiolytic Sedatives Hypnotics and Antipsychotics Etifoxine Hydrochloride (BANM, rINNM) Profile Etifoxin Hydrochloride; Étifoxine, Chlorhydrate d’; Etifoxini Hy- Febarbamate is a barbiturate with general properties similar to those of amobarbital (p.961). It has been used in the management H C O drochloridum; Hidrocloruro de etifoxina; Hoe-36801. 6-Chloro- 3 of anxiety, insomnia, and alcohol withdrawal symptoms. How- N 4-methyl-4-phenyl-3,1-benzoxazin-2-yl(ethyl)amine hydrochlo- ever, barbiturates are no longer considered appropriate in the ride. management of these conditions. Этифоксина Гидрохлорид Tetrabamate, a complex of febarbamate, difebarbamate, and N C17H17ClN2O,HCl = 337.2. phenobarbital, has been used similarly but was associated with CAS — 21715-46-8 (etifoxine); 56776-32-0 (etifoxine hy- the development of hepatitis. O N drochloride). 2 F ATC — N05BX03. Preparations ATC Vet — QN05BX03. Proprietary Preparations (details are given in Part 3) Multi-ingredient: Hung.: Atrium†. NOTE. The following terms have been used as ‘street names’ (see (BAN, rINN) p.vi) or slang names for various forms of flunitrazepam: Fluanisone Benzo; Circles; Date rape drug; Forget me drug; Forget pill; For- H Fluanison; Fluanisona; Fluanisoni; Fluanisonum; Haloanisone; MD- get-me pill; Forget-Me-Pill; Getting roached; La Rocha; La Ro- O N CH3 2028; R-2028; R-2167. 4′-Fluoro-4-[4-(2-methoxyphenyl)piper- che; Lunch money drug; Mexican valium; Pingus; R2; R-2; Rey- H3C azin-1-yl]butyrophenone. nolds; Rib; Rick James Biatch; Roach 2; Roach-2; Roaches; N Roachies; Roapies; Robutal; Rochas dos; Roche; Roches; Флуанизон Rolpes; Roofie; Roofies; Roopies; Rope; Rophies; Rophy; Rop- C21H25FN2O2 = 356.4. ies; Roples; Ropples; Row-shay; Ruffies; Ruffles; Sedexes; CAS — 1480-19-9. Wolfies. Cl ATC — N05AD09. Pharmacopoeias. In Eur. (see p.vii) and Jpn. ATC Vet — QN05AD09. (etifoxine) Ph. Eur. 6.2 (Flunitrazepam). A white or yellowish crystalline powder. Practically insoluble in water; slightly soluble in alco- hol; soluble in acetone. Protect from light. Profile Etifoxine hydrochloride is an anxiolytic used for the short-term treatment of anxiety (p.952). It is given in usual oral doses of 150 Dependence and Withdrawal or 200 mg daily in 2 or 3 divided doses. O N As for Diazepam, p.987. Preparations N OCH3 Proprietary Preparations (details are given in Part 3) Adverse Effects, Treatment, and Precau- Fr.: Stresam. tions As for Diazepam, p.987. F Abuse. A WHO review1 concluded that flunitrazepam had a Etizolam (rINN) Pharmacopoeias. In BP(Vet). moderate abuse potential that might be higher than that of other AHR-3219; Étizolam; Etizolamum; Y-7131. 4-(2-Chlorophenyl)- BP(Vet) 2008 (Fluanisone). White or almost white to buff-col- benzodiazepines. It was reported that there was current evidence 2-ethyl-9-methyl-6H-thieno[3,2-f]-s-triazolo[4,3-a][1,4]diazepine. oured, odourless or almost odourless crystals or powder. It exhib- of widespread abuse of flunitrazepam among drug abusers, par- Этизолам its polymorphism. M.p. 72° to 76°. Practically insoluble in water; ticularly among those who used opioids or cocaine. freely soluble in alcohol, in chloroform, in ether, and in dilute so- C17H15ClN4S = 342.8. Flunitrazepam is tasteless and odourless and has been misused to CAS — 40054-69-1. lutions of organic acids. Protect from light. incapacitate the victim and produce amnesia in sexual assaults2 ATC — N05BA19. and drug-facilitated rape (‘date rape’).3 A 1-mg dose may pro- Profile 4 ATC Vet — QN05BA19. Fluanisone is a butyrophenone with general properties similar to duce impairment for 8 to 12 hours. Some manufacturers have those of haloperidol (p.1000). It has been used in the manage- incorporated a blue dye into flunitrazepam tablets to increase vis- ment of agitated states in psychiatric patients and as anaesthetic ibility when placed into drinks but caution is still necessary as it N has been reported that blue tropical drinks and punches are being H C premedication. 3 N used to overcome this.3 Fluanisone is used in veterinary medicine for neuroleptanalgesia. N 1. WHO expert committee on drug dependence: twenty-ninth re- port. WHO Tech Rep Ser 856 1995. Available at: http:// S libdoc.who.int/trs/WHO_TRS_856.pdf (accessed 21/08/08) 2. Simmons MM, Cupp MJ. Use and abuse of flunitrazepam. Ann N Fludiazepam (rINN) Pharmacother 1998; 32: 117–19. Fludiazépam; Fludiazepamum; ID-540. 7-Chloro-5-(2-fluorophe- 3. National Institute on Drug Abuse. Rohypnol and GHB (issued H3C May 2006). Available at: http://www.nida.nih.gov/PDF/ Cl nyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one. Infofacts/Rohypnol06.pdf (accessed 21/08/08) Флудиазепам 4. Smith KM, et al. Club drugs: methylenedioxymethampheta- C H ClFN O = 302.7. mine, flunitrazepam, ketamine hydrochloride, and γ-hydroxybu- 16 12 2 tyrate. Am J Health-Syst Pharm 2002; 59: 1067–76. CAS — 3900-31-0. ATC — N05BA17. Breast feeding. Concentrations in breast milk the morning af- Pharmacopoeias. In Jpn. ATC Vet — QN05BA17. ter a single evening 2-mg dose of flunitrazepam were considered Profile to be too low to produce clinical effects in breast-fed infants, al- Etizolam is a short-acting benzodiazepine derivative with gener- though accumulation in the milk might occur after repeated use.1 al properties similar to those of diazepam (p.986). It is given for O 1. Kanto J, et al. Placental transfer and breast milk levels of fluni- the short-term treatment of insomnia (p.957) and anxiety disor- trazepam. Curr Ther Res 1979; 26: 539–46. ders (p.952) in oral doses of up to 3 mg daily in divided doses or Local reactions. Of 43 patients given a single intravenous dose CH3 as a single dose at night. N N of flunitrazepam 1 to 2 mg, two had local thrombosis 7 to 10 Preparations days later.1 The incidence was lower than in those given di- azepam [in solution]. However, there was little difference in the Proprietary Preparations (details are given in Part 3) Ital.: Depas; Pasaden; Jpn: Depas. incidence of local reactions after intravenous use of fluni- trazepam and diazepam in another study.2 F 1. Hegarty JE, Dundee JW. Sequelae after the intravenous injection of three benzodiazepines—diazepam, lorazepam, and fluni- Febarbamate (rINN) Cl trazepam. BMJ 1977; 2: 1384–5. Fébarbamate; Febarbamato; Febarbamatum; Go-560. 1-(3-Bu- 2. Mikkelsen H, et al. Local reactions after iv injections of di- Pharmacopoeias. In Jpn. azepam, flunitrazepam and isotonic saline. Br J Anaesth 1980; toxy-2-carbamoyloxypropyl)-5-ethyl-5-phenylbarbituric acid. 52: 817–19. Фебарбамат Profile Porphyria. Flunitrazepam has been associated with acute at- Fludiazepam is a short-acting benzodiazepine with general prop- C20H27N3O6 = 405.4. tacks of porphyria and is considered unsafe in porphyric patients. CAS — 13246-02-1. erties similar to those of diazepam (p.986). It has been used in the ATC — M03BA05. short-term treatment of anxiety disorders. ATC Vet — QM03BA05. Interactions As for Diazepam, p.989. O Flunitrazepam (BAN, USAN, rINN) Pharmacokinetics H3C HN Flunitratsepaami; Flunitrazépam; Flunitrazepám; Flunitrazepamas; Flunitrazepam is readily absorbed from the gastroin- CH O 3 Flunitrazepamum; Ro-5-4200. 5-(2-Fluorophenyl)-1,3-dihydro- testinal tract. About 77 to 80% is bound to plasma pro- 1-methyl-7-nitro-1,4-benzodiazepin-2-one. teins. It is extensively metabolised in the liver and ex- O N Флунитразепам creted mainly in the urine as metabolites (free or O O C16H12FN3O3 = 313.3. conjugated). Its principal metabolites are 7-aminoflu- O CAS — 1622-62-4. nitrazepam and N-desmethylflunitrazepam; N-des- H2N ATC — N05CD03. methylflunitrazepam is reported to be pharmacologi- ATC Vet — QN05CD03. cally active. The elimination half-life of flunitrazepam Etifoxine Hydrochloride/Flupentixol 997 is reported to be between 16 and 35 hours. Fluni- Flupentixol Hydrochloride (BANM, rINNM) phrenia (p.955) and other psychoses. Unlike chlorpro- trazepam crosses the placental barrier and is distributed Flupenthixol Dihydrochloride; Flupenthixol Hydrochloride; Flu- mazine, an activating effect has been ascribed to flu- into breast milk. pentiksol Dihidroklorür; Flupentiksolidihydrokloridi; Flupentikso- pentixol, and it is not indicated in overactive or manic ◊ References. lio dihidrochloridas; Flupentixol, Chlorhydrate de; Flupentixol, patients. Flupentixol has also been used for its antide- dichlorhydrate de; Flupentixol-dihidroklorid; Flupentixol-dihy- 1. Davis PJ, Cook DR. Clinical pharmacokinetics of the newer in- pressant properties. travenous anaesthetic agents. Clin Pharmacokinet 1986; 11: drochlorid; Flupentixoldihydroklorid; Flupentixoli dihydrochlori- 18–35. dum; Flupentixoli Hydrochloridum; Hidrocloruro de flupentixol. Flupentixol is given orally as the hydrochloride al- 2. Pariente-Khayat A, et al. Pharmacokinetics and tolerance of flu- Флупентиксола Гидрохлорид though doses are expressed in terms of the base; flu- nitrazepam in neonates and in infants. Clin Pharmacol Ther pentixol hydrochloride 3.5 mg is equivalent to about 1999; 66: 136–9. C H F N OS,2HCl = 507.4. 23 25 3 2 3 mg of flupentixol. Flupentixol is also given as the CAS — 2413-38-9. Pregnancy. Concentrations of flunitrazepam in umbilical-vein longer-acting decanoate ester by deep intramuscular and umbilical-artery plasma were lower than those in maternal ATC — N05AF01. injection. The long-acting preparation available in the venous plasma about 11 to 15 hours after a dose of flunitrazepam ATC Vet — QN05AF01. 1 mg in 14 pregnant women; concentrations in amniotic fluid UK contains flupentixol decanoate as the cis(Z)-iso- were lower still.1 Pharmacopoeias. In Eur. (see p.vii). mer (see Action, below) and doses are expressed in Ph. Eur. 6.2 (Flupentixol Dihydrochloride; Flupentixol Hydro- 1. Kanto J, et al. Placental transfer and breast milk levels of fluni- terms of the amount of cis(Z)-flupentixol decanoate. trazepam. Curr Ther Res 1979; 26: 539–46. chloride BP 2008). A white or almost white powder. Very soluble in water; soluble in alcohol; practically insoluble in dichlo- The usual initial oral dose for the treatment of psycho- romethane.