1870 Local Anaesthetics Preparations pore: Alcaine; Switz.: Alcaine; Turk.: Alcaine; Opticaine; USA: Ak-Taine; Alcaine; Ocu-Caine; Ophthetic; Parcaine; Venez.: Alcaine; Oftaine†; Poen- (details are given in Part 3) caina. Proprietary Preparations CH3 Multi-ingredient: Spain: Detraine. O Multi-ingredient: Canad.: Fluoracaine†; USA: Fluoracaine; Fluorocaine. N CH3 O Quinisocaine Hydrochloride (BANM, rINNM) H3C Propipocaine (rINN) O Chinisocainum Hydrochloride; Dimethisoquin Hydrochloride Propipocaína; Propipocaïne; Propipocainum; Propoxypipero- (USAN); Dimethisoquinium Chloride; Hidrocloruro de quinisocaí- NH2 caine. 3-Piperidino-4′-propoxypropiophenone. na; Quinisocaïne, Chlorhydrate de; Quinisocaini Hydrochlori- (proxymetacaine) dum. 2-(3-Butyl-1-isoquinolyloxy)-NN-dimethylethylamine hy- Пропипокаин drochloride. C17H25NO2 = 275.4. Хинизокаина Гидрохлорид CAS — 3670-68-6. NOTE. PROX is a code approved by the BP 2008 for use on single unit doses of eye drops containing proxymetacaine hydrochlo- C17H24N2O,HCl = 308.8. ride where the individual container may be too small to bear all CAS — 86-80-6 (quinisocaine); 2773-92-4 (quinisocaine the appropriate labelling information. PROXFLN is a similar hydrochloride). O code approved for eye drops containing proxymetacaine hydro- ATC — D04AB05. chloride and fluorescein sodium. ATC Vet — QD04AB05. N Pharmacopoeias. In Br. and US. BP 2008 (Proxymetacaine Hydrochloride). A white or almost H3C CH3 white, odourless or almost odourless, crystalline powder. Soluble O in water and in chloroform; very soluble in dehydrated alcohol; N practically insoluble in ether. A 1% solution in water has a pH of O CH Profile 5.7 to 6.4. Protect from light. 3 Propipocaine is a local anaesthetic (p.1850) that has been used USP 31 (Proparacaine Hydrochloride). A white to off-white, or for surface anaesthesia. faintly buff-coloured, odourless, crystalline powder. Soluble in N water, in warm alcohol, and in methyl alcohol; insoluble in ether CH and in benzene. 3 (quinisocaine) Propoxycaine Hydrochloride (rINNM) Adverse Effects, Treatment, and Precau- tions Hidrocloruro de propoxicaína; Propoxycaïne, Chlorhydrate de; Profile Propoxycaini Hydrochloridum; Propoxycainium Chloride. 2-Di- As for Local Anaesthetics in general, p.1850. Quinisocaine hydrochloride is a local anaesthetic (p.1850) that ethylaminoethyl 4-amino-2-propoxybenzoate hydrochloride. A severe immediate-type corneal reaction to has been used as a surface anaesthetic in the form of an ointment or cream in a concentration of 0.5% for the relief of pruritus, ano- Пропоксикаина Гидрохлорид proxymetacaine may rarely occur. Allergic contact genital or anorectal irritation, and minor skin conditions. It has dermatitis has also been reported. also been used as suppositories. C16H26N2O3,HCl = 330.9. CAS — 86-43-1 (propoxycaine); 550-83-4 (propoxycaine Effects on the skin. Exacerbation of Stevens-Johnson syn- Preparations 1 hydrochloride). drome has been reported in a woman after ophthalmic anaesthe- Proprietary Preparations (details are given in Part 3) sia with proxymetacaine hydrochloride. Fr.: Quotane; Ger.: Haenal; Isochinol†; Switz.: Isochinol. 1. Ward B, et al. Dermatologic reaction in Stevens-Johnson syn- Multi-ingredient: Fr.: Rectoquotane. drome after ophthalmic anesthesia with proparacaine hydrochlo- CH3 ride. Am J Ophthalmol 1978; 86: 133–5. O O N CH3 Interactions Ropivacaine Hydrochloride For interactions associated with local anaesthetics, see O (BANM, rINNM) CH3 p.1851. AL-281; Hidrocloruro de ropivacaína; Ropivacaïne, chlorhydrate Pharmacokinetics de; Ropivacaini hydrochloridum; Ropivakaiinihydrokloridi; Ropi- See under Local Anaesthetics, p.1852. vakain Hidroklorür; Ropivakainhydroklorid. (S)-2′,6′-Dimethyl-1- NH2 propylpiperidine-2-carboxanilide hydrochloride monohydrate. Ропивакаина Гидрохлорид Uses and Administration (propoxycaine) C17H26N2O,HCl,H2O = 328.9. Proxymetacaine hydrochloride, a meta-aminobenzoic CAS — 84057-95-4 (ropivacaine); 98717-15-8 (anhy- Pharmacopoeias. In US. acid ester, is a local anaesthetic with actions and uses drous ropivacaine hydrochloride); 132112-35-7 (ropi- USP 31 (Propoxycaine Hydrochloride). A white odourless crys- similar to those described on p.1852. It is used for sur- vacaine hydrochloride monohydrate). talline solid. It discolours on prolonged exposure to light and air. face anaesthesia (p.1853) in ophthalmology in a con- ATC — N01BB09. Soluble 1 in 2 of water, 1 in 10 of alcohol, and 1 in 80 of ether; centration of 0.5%. Proxymetacaine is of similar ATC Vet — QN01BB09. practically insoluble in acetone and in chloroform. A 2% solu- potency to tetracaine in equal concentrations and in- tion in water has a pH of about 5.4. Protect from light. duces anaesthesia within about 20 seconds. The dura- H C Profile 3 tion of action may be 15 minutes or longer. Instillation H3C O Propoxycaine hydrochloride, a para-aminobenzoic acid ester, is of 1 or 2 drops permits tonometry after 30 seconds. For a local anaesthetic (p.1850). It has been used with procaine hy- removal of foreign bodies or sutures from the cornea 1 N drochloride and a vasoconstrictor for infiltration anaesthesia and N nerve block in dental procedures. Propoxycaine has a more rapid or 2 drops are instilled every 5 to 10 minutes for up to H CH onset and a longer duration of action than that of procaine. 3 applications, or 1 or 2 drops are instilled 2 to 3 min- 3 utes before the procedure. For deeper anaesthesia such Preparations as needed for cataract extraction 1 drop is instilled eve- (ropivacaine) USP 31: Propoxycaine and Procaine Hydrochlorides and Levonordefrin ry 5 to 10 minutes to a total of 5 to 7 applications. Injection; Propoxycaine and Procaine Hydrochlorides and Norepinephrine Pharmacopoeias. In Eur. (see p.vii) and US. Bitartrate Injection. Trigeminal neuralgia. There have been anecdotal reports that Ph. Eur. 6.2 (Ropivacaine Hydrochloride Monohydrate). A proxymetacaine eye drops relieved trigeminal neuralgia (p.9) re- white or almost white, crystalline powder. Soluble in water and fractory to carbamazepine.1,2 However, a controlled study failed in alcohol; slightly soluble in dichloromethane. pH of a 2% solu- to demonstrate any benefit.3 tion in water is 4.5 to 6.0. Proxymetacaine Hydrochloride 1. Zavon MR, Fichte CM. Trigeminal neuralgia relieved by oph- USP 31 (Ropivacaine Hydrochloride). A white crystalline pow- thalmic anesthetic. JAMA 1991; 265: 2807. der. Soluble in water. A 1% solution in water has a pH of 4.5 to (BANM, rINNM) 2. Zavon MR, Fichte CM. Trigeminal neuralgia relieved by optical 6.0. anesthesia. JAMA 1991; 266: 1649. Hidrocloruro de proximetacaína; Proksimetakain Hidroklorür; 3. Kondziolka D, et al. The effect of single-application topical oph- Proparacaine Hydrochloride; Proparakain Hidroklorür; Prox- thalmic anesthesia in patients with trigeminal neuralgia: a rand- Adverse Effects, Treatment, and Precau- ymétacaïne, Chlorhydrate de; Proxymetacaini Hydrochloridum. omized double-blind placebo-controlled trial. J Neurosurg 1994; tions 80: 993–7. 2-Diethylaminoethyl 3-amino-4-propoxybenzoate hydrochlo- As for Local Anaesthetics in general, p.1850. ride. Preparations Ropivacaine is contra-indicated for use in intravenous Проксиметакаина Гидрохлорид BP 2008: Proxymetacaine Eye Drops; regional anaesthesia (Bier’s block) and for paracervical USP 31: Fluorescein Sodium and Proparacaine Hydrochloride Ophthalmic C16H26N2O3,HCl = 330.9. Solution; Proparacaine Hydrochloride Ophthalmic Solution. block in obstetrics. CAS — 499-67-2 (proxymetacaine); 5875-06-9 Proprietary Preparations (details are given in Part 3) Effects on the cardiovascular system. Ropivacaine is struc- (proxymetacaine hydrochloride). Arg.: Anestalcon; Poencaina; Austral.: Alcaine; Ophthetic†; Belg.: Alcaine; turally related to bupivacaine, but data from extensive animal Braz.: Anestalcon; Visonest; Canad.: Ak-Taine; Alcaine; Diocaine†; Oph- studies suggest that ropivacaine may be less cardiotoxic than ATC — S01HA04. thetic†; Chile: Anestalcon; Ger.: Proparakain-POS; Gr.: Alcaine; Hong 1 2 Kong: Alcaine; Malaysia: Alcaine; Mex.: Alcaine; Norw.: Alcaine; NZ: bupivacaine. Results from a study in 12 healthy male volun- ATC Vet — QS01HA04. Ophthetic; Philipp.: Alcaine; Pol.: Alcaine; Rus.: Alcaine (Алкаин); Singa- teers support these data; at doses producing CNS symptoms car- Propipocaine/Tetracaine 1871 diovascular changes, such as depression of conduction and di- dural block to establish a block for postoperative Tetracaine Hydrochloride (BANM, rINNM) astolic function, were less pronounced with ropivacaine than pain relief are 25 to 75 mg (5 to 15 mL) as a 0.5% Amethocaine Hydrochloride; Dicainum; Hidrocloruro de tet- with bupivacaine. solution or 37.5 to 112.5 mg (5 to 15 mL) as a 0.75% racaína; Tétracaïne, chlorhydrate de; Tetracaini hydrochloridum; 1. Cederholm I. Preliminary risk-benefit analysis of ropivacaine in labour and following surgery. Drug Safety 1997; 16: 391–402. solution; the actual dose used depends on the level of Tetracainii Chloridum; Tetrakaiinihydrokloridi; Tetrakain Hid- 2. Knudsen K, et al. Central nervous and cardiovascular effects of the injection. roklorür; Tetrakain hydrochlorid; Tetrakainhidroklorid; Tetrakain- i.v. infusions of ropivacaine, bupivacaine and placebo in volun- •For peripheral nerve block of major nerves such as hydroklorid; Tetrakaino hidrochloridas; Tetrakainy chlorowodor- teers. Br J Anaesth 1997; 78: 507–14. ek. the brachial plexus, typical doses are 175 to 250 mg Interactions (35 to 50 mL) as a 0.5% solution; 225 to 300 mg (30 Тетракаина Гидрохлорид For interactions associated with local anaesthetics, see C15H24N2O2,HCl = 300.8. to 40 mL) as a 0.75% solution has also been recom- CAS — 136-47-0. p.1851. mended for brachial plexus block. ATC — C05AD02; D04AB06; N01BA03; S01HA03. Giving ropivacaine with general anaesthetics, opioid •For infiltration anaesthesia and field block up to ATC Vet — QC05AD02; QD04AB06; QN01BA03; analgesics, or drugs structurally related to amide-type 200 mg (40 mL) as a 0.5% solution or up to 225 mg QS01HA03. local anaesthetics (e.g. certain antiarrhythmics) may (30 mL) as a 0.75% solution may be used. NOTE. TET is a code approved by the BP 2008 for use on single result in potentiation of adverse effects. unit doses of eye drops containing tetracaine hydrochloride • In the management of acute pain ropivacaine hy- where the individual container may be too small to bear all the The metabolism of ropivacaine is mediated by the cy- drochloride is used as a 0.2% solution for epidural appropriate labelling information. tochrome P450 isoenzyme CYP1A2 and the potential block (0.5% solutions may be used for infiltration). Pharmacopoeias. In Chin., Eur. (see p.vii), Int., Jpn, US, and exists for interactions between ropivacaine and other Doses for lumbar epidural block are 20 to 40 mg (10 Viet. drugs that inhibit or act as a substrate for this isoen- to 20 mL) as an initial bolus followed by 20 to 30 mg Ph. Eur. 6.2 (Tetracaine Hydrochloride). A white or almost zyme. Prolonged use of ropivacaine should be avoided (10 to 15 mL) at intervals of not less than 30 min- white, slightly hygroscopic, polymorphic, crystalline powder. in patients treated with potent CYP1A2 inhibitors, utes. Alternatively, 12 to 20 mg (6 to 10 mL) per Freely soluble in water; soluble in alcohol. A 1% solution in wa- ter has a pH of 4.5 to 6.5. Store in airtight containers. Protect such as fluvoxamine. Plasma concentrations of ropi- hour may be given as a continuous epidural infusion; from light. vacaine may be reduced by enzyme-inducing drugs if additional pain relief is required, doses of up to USP 31 (Tetracaine Hydrochloride). A fine, white, odourless, such as rifampicin. 28 mg (14 mL) per hour may be given. Doses for hygroscopic, polymorphic, crystalline powder. Very soluble in thoracic epidural block are 12 to 28 mg (6 to 14 mL) water; soluble in alcohol; insoluble in ether and in benzene. Its Pharmacokinetics per hour as a continuous infusion. solutions are neutral to litmus. Store in airtight containers. Pro- tect from light. Ropivacaine is about 94% bound to plasma proteins. •For infiltration anaesthesia doses are 2 to 200 mg (1 The terminal elimination half-life has been reported to to 100 mL) as a 0.2% solution or 5 to 200 mg (1 to Adverse Effects and Treatment be 1.8 hours. It is extensively metabolised in the liver, 40 mL) as a 0.5% solution. As for Local Anaesthetics in general, p.1850. predominantly by aromatic hydroxylation which is • In neonates, infants, and children aged up to 12 mediated by the cytochrome P450 isoenzyme Tetracaine has high systemic toxicity. Absorption of years, ropivacaine hydrochloride may be used for tetracaine from mucous membranes is rapid and ad- CYP1A2; the isoenzyme CYP3A4 plays a minor role the management of peri- and postoperative pain. A in the metabolism of ropivacaine. The metabolites are verse reactions can occur abruptly without the appear- 0.2% solution is given in a dose of 2 mg/kg ance of prodromal signs or convulsions; fatalities have excreted mainly in the urine; about 1% of a dose is ex- (1 mL/kg) to achieve a caudal epidural block. creted as unchanged drug. Some metabolites also have occurred. a local anaesthetic effect but less than that of ropi- ◊ References. A stinging sensation may occur when tetracaine is used 1. Markham A, Faulds D. Ropivacaine: a review of its pharmacol- vacaine. Ropivacaine crosses the placenta. ogy and therapeutic use in regional anaesthesia. Drugs 1996; 52: in the eye. Mild erythema at the site of application is See also under Local Anaesthetics, p.1852. 429–49. frequently seen with topical use; slight oedema or pru- 2. McClure JH. Ropivacaine. Br J Anaesth 1996; 76: 300–307. ritus occur less commonly. Blistering of the skin may 3. Morton C. Ropivacaine. Br J Hosp Med 1997; 58: 97–100. Uses and Administration 4. Stienstra R. The place of ropivacaine in anesthesia. Acta Anaes- occur. thesiol Belg 2003; 54: 141–8. 1 Ropivacaine hydrochloride is a local anaesthetic of the 5. Zink W, Graf BM. Benefit-risk assessment of ropivacaine in the Urethral stricture. There has been a report of a sudden in- amide type with actions and uses similar to those de- management of postoperative pain. Drug Safety 2004; 27: crease in the incidence of urethral stricture after transurethral sur- scribed on p.1852. It is a long-acting local anaesthetic, 1093–1114. gery, which may have been due to an increase in the concentra- 6. Simpson D, et al. Ropivacaine: a review of its use in regional although onset and duration of action are dependent tion of tetracaine hydrochloride in the lubricant gel from 0.1 to anaesthesia and acute pain management. Drugs 2005; 65: 3%. 2675–2717. upon the site of injection; the presence of a vasocon- 1. Pansadoro V. Role of local anaesthetics in urethral strictures af- strictor such as adrenaline has no effect. Ropivacaine is Preparations ter transurethral surgery. Lancet 1990; 336: 64. used for epidural block, peripheral nerve block, and in- USP 31: Ropivacaine Hydrochloride Injection. filtration anaesthesia and field block, but is contra-indi- Proprietary Preparations (details are given in Part 3) Precautions cated for obstetric paracervical block and for use in in- Arg.: Naropin; Austral.: Naropin; Austria: Naropin; Belg.: Naropin; As for Local Anaesthetics in general, p.1851. Braz.: Naropin; Ropi; Canad.: Naropin; Chile: Naropin; Cz.: Naropin; travenous regional anaesthesia (Bier’s block). (Local Denm.: Naropin; Fin.: Naropin; Fr.: Naropeine; Ger.: Naropin; Gr.: Naro- Tetracaine should not be applied to inflamed, trauma- anaesthetic techniques are discussed on p.1853.) At peine; Hong Kong: Naropin; Hung.: Naropin; Indon.: Naropin; Irl.: Naropin; Israel: Narop; Ital.: Naropina; Malaysia: Naropin; Mex.: Naro- tised, or highly vascular surfaces. It should not be used high doses ropivacaine produces surgical anaesthesia, pin; Neth.: Naropin; Norw.: Naropin; NZ: Naropin; Philipp.: Naropin; to provide anaesthesia for bronchoscopy or cystosco- whereas at lower doses it is used for the management Pol.: Naropin; Port.: Naropeine; Rus.: Naropin (Наропин); S.Afr.: Naro- pin; Singapore: Naropin; Spain: Naropin; Swed.: Narop; Switz.: Naropin; py, as lidocaine is a safer alternative. of acute pain such as labour pain (p.7) and in postoper- Thai.: Naropin†; Turk.: Naropin; UK: Naropin; USA: Naropin; Venez.: ative analgesia (p.4). Naropin†. Interactions Multi-ingredient: Austral.: Naropin with Fentanyl; NZ: Naropin with Like bupivacaine (p.1854), ropivacaine has a differen- Fentanyl. For interactions associated with local anaesthetics, see tial blocking effect on nerve fibres and, at the lowest p.1851. concentration used, there is good differentiation be- tween sensory and motor block. The onset and duration Pharmacokinetics Tetracaine (BAN, rINN) of sensory block produced by ropivacaine is generally See under Local Anaesthetics, p.1852. Tetracaine is re- similar to that obtained with bupivacaine but the motor Amethocaine; Tetracaína; Tétracaïne; Tetracainum; Tetrakaiini; ported to be about 15% bioavailable after application block is often slower in onset, shorter in duration, and Tetrakain. 2-Dimethylaminoethyl 4-butylaminobenzoate. of a 4% gel to intact skin, with a mean absorption and less intense. Тетракаин elimination half-life of about 75 minutes. C H N O = 264.4. Ropivacaine hydrochloride is given in concentrations 15 24 2 2 CAS — 94-24-6. Uses and Administration of 0.2 to 1%. The dosage depends on the site of injec- ATC — C05AD02; D04AB06; N01BA03; S01HA03. tion and the procedure used, as well as the status of the ATC Vet — QC05AD02; QD04AB06; QN01BA03; Tetracaine, a para-aminobenzoic acid ester, is a potent patient. The dose of ropivacaine should be reduced in QS01HA03. local anaesthetic with actions and uses similar to those the elderly, and in acutely ill or debilitated patients. A described on p.1852. It is used for surface anaesthesia test dose of lidocaine with adrenaline should be given and spinal block; its use in other local anaesthetic tech- CH before starting epidural block with ropivacaine to de- O 3 niques is restricted by its systemic toxicity. tect inadvertent intravascular administration. N Tetracaine is generally used as the hydrochloride in O •For surgical anaesthesia, doses of ropivacaine hy- CH3 solutions and creams, and as the base in gels or oint- drochloride for lumbar epidural block are 75 to ments. H3C N 150 mg (15 to 30 mL) as a 0.5% solution, or 112.5 to H For anaesthesia of the eye, solutions containing 0.5 to 187.5 mg (15 to 25 mL) as a 0.75% solution, or 150 1% tetracaine hydrochloride have been used; oint- to 200 mg (15 to 20 mL) as a 1% solution; for cae- Pharmacopoeias. In US. ments have also been used. Instillation of a 0.5% solu- USP 31 (Tetracaine). A white or light yellow waxy solid. M.p. sarean section, doses are 100 to 150 mg (20 to 41° to 46°. Very slightly soluble in water; soluble 1 in 5 of alco- tion produces anaesthesia within 25 seconds that lasts 30 mL) as a 0.5% solution or 112.5 to 150 mg (15 to hol and 1 in 2 of chloroform or of ether; soluble in benzene. Store for 15 minutes or longer and is suitable for use before 20 mL) as a 0.75% solution. Doses for thoracic epi- in airtight containers. Protect from light. minor surgical procedures. 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)