Tetryzoline Hydrochloride/Zipeprol Hydrochloride 1575 Preparations CAS — 526-36-3 (xylometazoline); 1218-35-5 (xylometa- Siozwo Akut†; Snup; stas Nasentropfen, Nasenspray†; Tussamag Na- zoline hydrochloride). senspray; Xylo; Xylo Siozwo†; Xylo-COMOD†; Xylo-POS; Gr.: Otrivin; Proprietary Preparations (details are given in Part 3) Otrivin-Menthol; Hong Kong: Decongestant Nasal Spray; Otrivin; Xyloma; Austral.: Spray-Tish; Austria: Rinorix; Belg.: Rhinospray; Cz.: Muconasal ATC — R01AA07; R01AB06; S01GA03. Hung.: Nasan; Novorin; Otrivin; Rhinathiol; Rhino-Stas; India: Decon; Plus; Ger.: Biciron; Ellatun; Rhinospray; Ital.: Rinogutt Spray-Fher; Neth.: Nazalin; Otrivin; Indon.: Otrivin; Irl.: Otrivine; Israel: Nazalet; Otrivin; Xy- Bisolnasal; Port.: Rhinospray; Spain: Rhinospray. ATC Vet — QR01AA07; QR01AB06; QS01GA03. lovit; Ital.: Neo Rinoleina; Otrivin; Respiro; Malaysia: Otrivin; Neth.: Kru- Multi-ingredient: Arg.: Dexa-Rhinospray N; Austral.: Spray-Tish Men- idvat Neusdruppels; Kruidvat Neusspray; Mucorhinyl; Otrivin; Xylo-CO- thol; Austria: Rhinospray Plus; Belg.: Dexa-Rhinospray; Ger.: Dexa Bici- MOD; Norw.: Naso; Nazaren; Otrivin; Xolin; Zymelin; NZ: Otrivine; Philipp.: Otrivin; Pol.: Otrivin; Xylogel; Xylorin; Port.: Otrivina; Rus.: Dli- ron; Oxy Biciron; Rhinospray Plus; Rhinospray sensitiv; Gr.: Dexa-Rhina- CH3 spray-N; Hung.: Rhinospray Plus; Irl.: Dexa-Rhinaspray Duo; Ital.: anos (Длянос); Grippostad Rhino (Гриппостад Рино); Halazolin Rinogutt Antiallergico Spray; Rinogutt Eucalipto-Fher; Neth.: Rhinospray (Галазолин); Olynth (Олинт); Otrivin (Отривин); Rhinonorm met menthol; Rus.: Adrianol (Адрианол); Spain: Rhinospray Antialergico; N (Ринонорм); Rhinostop (Риностоп); Suprima-Nos (Суприма-Ноз); Tyzine UK: Dexa-Rhinaspray Duo†. Xylo (Тизин Ксило); Xymelin (Ксимелин); S.Afr.: Otrivin; Singapore: Ot- rivin; Spain: Amidrin; Idasal; Otrivin; Rinoblanco; Swed.: Nasoferm; Otriv- HN in; Zymelin; Switz.: Nasben; Nasobol Xylo; Olynth; Otrivin; Rhinostop; (H3C)3C CH3 Rhume†; Rinosedin; Xylo-Mepha; Thai.: Otrivin; Turk.: Naze; Otrivine; Rinizol; Xylo-COMOD; UAE: Xylolin; UK: Non-Drowsy Sudafed Decon- Tuaminoheptane Sulfate (rINNM) ⊗ (xylometazoline) gestant Nasal Spray; Otradrops; Otraspray; Otrivine; Tixycolds Cold and Sulfato de tuaminoheptano; Tuaminoheptane, Sulfate de; Tuami- Allergy; USA: 4-Way Moisturizing Relief; Otrivin. noheptane Sulphate (BANM); Tuaminoheptani Sulfas. Multi-ingredient: Chile: Bacitopic Compuesto; Nasomin; Rinobanedif; Pharmacopoeias. In Eur. (see p.vii) and US. Denm.: Otrivin Menthol; Fin.: Otrivin Menthol; Ger.: Lomupren composi- Туаминогептана Сульфат Ph. Eur. 6.2 (Xylometazoline Hydrochloride). A white or almost tum†; Nasic; Irl.: Otrivine-Antistin; Israel: Aforinol; Ital.: Inalar; Malaysia: Rynacrom Compound†; Mex.: Rinadex Compuesto; Neth.: Otrivin Men- (C7H17N)2,H2SO4 = 328.5. white, crystalline powder. Freely soluble in water, in alcohol, and thol; NZ: Otrivine Menthol; Otrivine-Antistin; Swed.: Otrivin Menthol; CAS — 6411-75-2. in methyl alcohol. Protect from light. Switz.: Lomusol-X†; Muco-Trin†; Triofan; Thai.: Rynacrom Compound†; ATC — R01AA11; R01AB08. USP 31 (Xylometazoline Hydrochloride). A white to off-white, Turk.: Rynacrom Compound; UK: Otrivine-Antistin; Rynacrom Com- ATC Vet — QR01AA11; QR01AB08. odourless, crystalline powder. Soluble 1 in 35 of water; freely pound†. soluble in alcohol; sparingly soluble in chloroform; practically insoluble in ether and in benzene. pH of a 5% solution in water CH3 is between 5.0 and 6.6. Store in airtight containers. Protect from light. Zipeprol Hydrochloride (rINNM)

H3C NH2 CERM-3024; Hidrocloruro de zipeprol; Zipéprol, Chlorhydrate Adverse Effects and Precautions de; Zipeproli Hydrochloridum. α-(α-Methoxybenzyl)-4-(β-meth- (tuaminoheptane) As for Naphazoline, p.1565. oxyphenethyl)-1-piperazineethanol dihydrochloride. Зипепрола Гидрохлорид Profile Interactions Tuaminoheptane is a volatile sympathomimetic (p.1407) that has C23H32N2O3,2HCl = 457.4. been used as the sulfate for the symptomatic relief of nasal con- Since xylometazoline is absorbed through the mucosa CAS — 34758-83-3 (zipeprol); 34758-84-4 (zipeprol hy- gestion. Tuaminoheptane has also been used in the form of the interactions may follow topical application. The BNF drochloride). carbonate. considers that all sympathomimetic nasal decongest- ATC — R05DB15. Preparations ants may cause a hypertensive crisis if used during ATC Vet — QR05DB15. Proprietary Preparations (details are given in Part 3) treatment with an MAOI. For the interactions of sym- Multi-ingredient: Braz.: Rinofluimucil; Fr.: Rhinofluimucil; Ger.: Rinoflu- pathomimetics in general, see p.1407. imucil-S†; Hong Kong: Rinofluimucil; Hung.: Rinofluimucil; Ital.: Rinoflui- CH3 mucil; Port.: Rinofluimucil; Rus.: Rinofluimucil (Ринофлуимуцил); Spain: Rinoflumil; Switz.: Rinofluimucil; Thai.: Rinofluimucil. Uses and Administration O Xylometazoline is a direct-acting sympathomimetic (p.1408) with marked alpha-adrenergic activity. It is a NN Tymazoline Hydrochloride (BANM) ⊗ vasoconstrictor which reduces swelling and congestion 2-Thymyloxymethyl-2-imidazoline Hydrochloride; Timazolina, when applied to mucous membranes. The effect begins COHOH hidrocloruro de; Tymazolini Hydrochloridum; Tymazoliny chlo- within 5 to 10 minutes of application and lasts for up to 3 rowodorek. 2-(2-Isopropyl-5-methylphenoxymethyl)-2-imidazo- 10 hours. (zipeprol) line hydrochloride. Xylometazoline is used as the hydrochloride for the Тимазолина Гидрохлорид short-term symptomatic relief of nasal congestion Profile C14H20N2O,HCl = 268.8. (p.1548). A 0.1% solution of xylometazoline hydro- CAS — 24243-97-8 (tymazoline); 28120-03-8 (tymazo- Zipeprol is a centrally acting cough suppressant that is stated to line hydrochloride). chloride is applied topically as nasal drops or a spray have a peripheral action on bronchial spasm. It has been given as ATC — R01AA13. into each nostril two or three times daily. For children’s the hydrochloride, typically in an oral dose of 150 to 300 mg dai- ly in divided doses. There have been reports of abuse and over- ATC Vet — QR01AA13. doses, see Administration in Children, below. dosage producing neurological symptoms. Xylometazoline hydrochloride solution is instilled into Abuse and overdosage. Severe neurological symptoms have the eye as a conjunctival decongestant (see Conjuncti- CH3 been reported in young adults after habitual abuse of zipeprol for vitis, p.564). Preparations containing 0.05% xylometa- euphoria. Patients have presented with generalised seizures, fol- zoline hydrochloride with 0.5% antazoline sulfate are lowed by coma.1 One patient who ingested 750 mg of zipeprol H3C [over twice the maximum daily dose] had several opisthotonic H typical; 0.1% xylometazoline hydrochloride has also 2 N been used. crises and developed cerebral oedema. Symptoms of overdos- OCH3 age in children have included restlessness, somnolence, ataxia, Administration in children. Over-the-counter cough and choreic movements, forced deviation of the head and eyes, gen- 1,3 N cold preparations containing sympathomimetic decongestants eralised seizures, respiratory depression, and coma. Fatalities (including xylometazoline) should be used with caution in chil- have been reported. (tymazoline) dren and generally avoided in those under 2 years of age (see Dependence and withdrawal symptoms similar to those pro- p.1547). However, the BNFC suggests that, in certain circum- duced by opioids have been reported.4 WHO has assessed zipe- Pharmacopoeias. In Pol. stances, specialists may prescribe xylometazoline nasal drops for prol to have a moderate potential for dependence and liability for Profile children under 2 years in the short-term treatment of severe nasal abuse.5 Although zipeprol is a weak opioid agonist at high doses Tymazoline is a sympathomimetic that has been used as the hy- congestion which has not responded to sodium chloride nasal its toxicity and hallucinogenic and other psychotropic effects drochloride similarly to naphazoline (p.1565) for its local vaso- drops or inhalation of warm moist air. A 0.05% solution of xy- constitute a significant element in its abuse, and the public health constrictor effect in the symptomatic relief of nasal congestion lometazoline hydrochloride is licensed for use in children aged and social problems associated with such abuse were considered (p.1548). from 2 to 12 years; 1 or 2 drops are instilled into each nostril once substantial. or twice daily, for a maximum of 7 days. The BNFC suggests that Preparations 1. Moroni C, et al. Overdosage of zipeprol, a non-opioid antitus- younger children aged 3 months and over may be given similar sive agent. Lancet 1984; i: 45. Proprietary Preparations (details are given in Part 3) doses. 2. Perraro F, Beorchia A. Convulsions and cerebral oedema associ- Pol.: Thymazen; Thai.: Pernazene. Preparations ated with zipeprol abuse. Lancet 1984; i: 45–6. 3. Merigot P, et al. Les convulsions avec trois antitussifs dérivés BP 2008: Xylometazoline Nasal Drops; substitués dé la pipérazine (zipéprol, éprazinone, éprozinol). Ann USP 31: Xylometazoline Hydrochloride Nasal Solution. Pediatr (Paris) 1985; 32: 504–11. Xylometazoline Hydrochloride Proprietary Preparations (details are given in Part 3) 4. Mallaret MP, et al. Zipeprol: primary dependence in an unaddict- ed patient. Ann Pharmacother 1995; 29: 540. (BANM, rINNM) ⊗ Arg.: Nastizol; Otrivina; Austral.: Otrivin; Austria: Olynth; Otrivin; Ratio- Soft; Xylo-COMOD; Belg.: Nasa Rhinathiol; Nasasinutab; Nuso-San; Otri- 5. WHO. WHO expert committee on drug dependence: twenty- Hidrocloruro de xilometazolina; Ksilometazolin Hidroklorür; Ksi- vine Anti-Rhinitis; Rhinidine†; Braz.: Orlaxyl†; Otrivina; Canad.: Balminil ninth report. WHO Tech Rep Ser 856 1995. Also available at: Nasal Decongestant; Certified Decongestant; Decongest†; Decongestant http://whqlibdoc.who.int/trs/WHO_TRS_856.pdf (accessed lometazolino hidrochloridas; Ksylometatsoliinihydrokloridi; Ksy- Nasal Spray; Decongestant Nose Drops; Nasal Decongestant; Otrivin; Cz.: 11/05/07) lometazoliny chlorowodorek; Xilometazolinhidroklorid; Xy- Dr Rentschler Snupfenspray†; Dr Rentschler Snupfentropfen†; Mar Rhino; lométazoline, chlorhydrate de; Xylometazolinhydro; Xylometa- Nasenspray AL; Nasentropfen AL; Olynth; Otrivin; Rhino-Stas; Xylo-CO- Preparations MOD; Denm.: Otrivin; Passagen; Zymelin; Fin.: Naso-Ratiopharm; Naso- zolin-hydrochlorid; Xylometazolini hydrochloridum. 2-(4-tert- lin; Otrivin; Zymelin†; Ger.: Balkis; Gelonasal; Imidin K†; Imidin N; Mentopin Proprietary Preparations (details are given in Part 3) Butyl-2,6-dimethylbenzyl)-2-imidazoline hydrochloride. Nasenspray†; Nasan; Nasengel; Nasengel AL; Nasenspray; Nasenspray AL; Chile: Frenotos; Gr.: Dovavixin†; Duo-Extolen†; Jactuss†; Mex.: Res- Nasenspray E; Nasenspray K; Nasenspray-CT; Nasentropfen AL; Nasentro- pilene†; Tusigen; Venez.: Coloplex†. Ксилометазолина Гидрохлорид pfen E; Nasentropfen K; Nasentropfen Stada; Olynth; Otriven; Otriven ge- C16H24N2,HCl = 280.8. gen Schnupfen; Rapako xylo; Rhinex mit Xylometazolin; schnupfen endrine; The symbol † denotes a preparation no longer actively marketed The symbol ⊗ denotes a substance whose use may be restricted in certain sports (see p.vii)