2009

soluble in alcohol. A 5% solution in water has a pH of methazolamide in a patient.1 Drug-induced hypersensi­ between 4.5 and 6.5. Protect from light. tivity was suspected as the cause of the reaction. USP 36: (Levobunolol Hydrochloride). A white odourless l. Krivoy N, et al. Methazolamide-induced hepatitis and pure RBC aplasia. 141: crystalline powder. Soluble in water and in methyl alcohol; Arch Intern Med 1981; 1229-30. slightly soluble in alcohol and in chloroform. A 5% solution in water has a pH between 4.5 and 6.5. Pharmacokinetics Methazolamide is absorbed from the gastrointestinal tract Uses and Administration more slowly than acetazolamide. It has been reported not to Levobunolol is a non-cardioselective beta blocker be extensively bound to plasma proteins, and to have a half­ (p. 1316.3). It is reported to lack intrinsic sympathomimetic life of about 14 hours. About 15 to 30% of the dose is excreted in the urine; the fate of the remainder is unknown. activity and membrane-stabilising properties. Nipradilol is a non-cardioselective beta blocker (p. 1316.3). Levobunolol is used as the hydrochlortde to reduce raised It is also reported to have direct vasodilating activity. It is intra-ocular pressure in open-angle glaucoma and ocular P.r�P?r<:Jii<:>n.� used in the management of glaucoma and ocular hypertension (p. 1999. 1). It begins to act 1 hour after . ProprietaryPreparations (details are given in Volume B) hypertension (p. 1999.1); eye drops containing nipradilol instillation with maximal effect seen between 2 and 6 hours; 0.05% are instilled twice daily. the effect may be maintained for up to 24 hours. Single-ingredient Preparations. China: Ni Mu Ke Si (Jil§51: iiJ ) ; Levobunolol hydrochloride is usually used as a 0.5% Thai.: Neptazane; USA: Neptazane. i Prepa. . rat..ons. . ophthalmic solution instilled once or twice daily; ...... alternatively a 0.25% solution may be instilled twice daily. PharmacopoeialPreparafions Proprietary Preparations (details are given in Volume B) USP 36: Methazolamide Tablets. Jpn: Adverse Effects, Treatment, and Precautions Single-ingredient Preparations. Hypadil. As for Beta Blockers, p. 1319.1. Interactions The interactions associated with beta blockers are discussed on p. 1321.2. Pharmacokinetics Some systemic absorption is reported to occur after topical application to the eye. After oral doses levobunolol is rapidly and almost completely absorbed from the gastrointestinal tract. It is extensively metabolised in the liver; the principal Description. An alkaloid obtained from the calabar bean metabolite. dihydrolevobunolol, is reported to possess beta­ NOTE. MPR is a code approved by the BP 2014 for use on (ordeal bean; chopnut), the seed of Physostigma venenosum blocking activity. The metabolites and some unchanged single unit doses of eye drops containing metipranolol (Legurninosae). drug are excreted in the urine. where the individual container may be too small to bear all Pharmacopoeias. In US. the appropriate labelling information. USP 36: (Physostigmine). An alkaloid usually obtained from Pharmacopoeias. In Br. the dried ripe seed of Physostigma venenosum (Leguminosae). ProprietaryPreparations (details are given in Volume B) BP 2014: (Metipranolol). A white crystalline powder. It is a white, odourless, microcrystalline powder which Practically insoluble in water; soluble in alcohol, in acetone, acquires a red tint on exposure to heat, light, or air, or on Arg.: Betagan; Levunolol; Aus­ Single-ingredient Preparations. and in methyl alcohol; dissolves in dilute mineral acids. The tral.: Betagant; Austria: Vistagan; Belg.: Betagan; Braz.: B­ contact with traces of metals. M.p. not lower than 103 Tablock; Betagan; Canad. : Betagan; Chile: Betagen; China: filtrate of a 2.5% suspension in water has a pH of 9.0 to 10.0. degrees. Slightly soluble in water; freely soluble in alcohol; Protect from light. Betagan ( I)Ht!!IE!); Cz.: Vistagan; Fr. : Betagan; Ger.: Vistagan; very soluble in chloroform and in dichloromethane; soluble Gr.: llunolol; Pentila; Vistagan; Hong Kong: Betagan; Hung.: in fixed oils and in benzene. Store in airtight containers. Vistagan; India: Betagan; Irl. : Betagan; Ital.: Vistagan; Malay­ Protect from light. sia: Betagan; Mex. : Betagan; Neth.: Betagan; NZ: Betagan; Uses and Administration Port.: Betagan; S.Afr.: Betagan; Singapore: Betagan; Spain: Metipranolol is a non-cardioselective beta blocker Betagan; Switz. : Vistagan; Thai.: Betagan; Turk.: Betagan; UK: (p. 1316.3). It is reported to be largely lacking in intrinsic Betagan; USA: Ak-Beta; Betagant; Venez.: Vistagan. sympathomimetic activity and membrane-stabilising prop­ erties. Canad.: Probetat. Mulfi-ingredientPreparafions. Metipranolol is used to reduce raised intra-ocular Pharmacopoeial Preparafions pressure in the management of open -angle glaucoma and BP 2014: Levobunolol Eye Drops; ocular hypertension (p. 1999. 1). Eye drops usually USP 36: Levobunolol Hydrochloride Ophthalmic Solution. containing metipranolol 0.1 or 0.3% are used twice daily. Metipranolol has also been given orally in the management of cardiovascular disorders. Methazolamide !BAN, riNN! ®

Adverse Effects, Treatment,. . and. Preca. utions ...... As for Beta Blockers, p. 1319.1. Conjunctivitis, conjunctival leucoplakia, transient sting­ ing, as well as other ocular adverse effects have been Ph. Eur. 8: (Physostigmine Salicylate). Colourless or almost reported with metipranolol eye drops. Granulomatous colourless crystals. It becomes red on exposure to air and anterior uveitis has been reported rarely; a high incidence light; the colour develops more quickly in the presence of reported in the UK may have been associated with changes moisture. Sparingly soluble in water; soluble in alcohol. A induced by radiation sterilisation of metipranolol eye drops 0.9% solution in water has a pH of 5.1 to 5.9. Store in in their final container, but this preparation is no longer airtight containers. Protect from light. Aqueous solutions available. are unstable. Pharmacopoeias. In US. USP 36: (Physostigmine Salicylate). White, shining, USP 36: (Methazolamide). A white or faintly yellow Interactions odourless, crystals or white powder. It acquires a red tint crystalline powder with a slight odour. Very slightly soluble The interactions associated with beta blockers are discussed on exposure to heat, light, or air, or on contact with traces of in water and in alcohol; slightly soluble in acetone; soluble l on p. 1321.2. metals for long periods. Soluble I in 75 of water, in 16 of in dimethylformamide. Protect from light. alcohol, 1 in 6 of chloroform. and I in 2 50 of ether. Store in i airtight containers at a temperature of 25 degrees, Uses and Administration ...... Prepar.a...... t ons..... excursions permitted between 15 degrees and 30 degrees . . . . (details are given in Volume B) Protect from light. Methazolamide is an inhibitor of carbonic anhydrase with ProprietaryPreparations actions similar to those of acetazolamide (p. 2001.1). It is Single-ingredient Preparations. Austria: Beta-Ophtiole; Belg_: Stability. See p. 2010.1. used in the treatment of glaucoma (p. 1999.1) in oral doses Beta-Ophtiole; Braz_; Beta-Ophtiole; Cz.: Trimepranol; Ger.: of 50 to IOOmg two or three times daily. Its action is less Betamann; Ital.: Turoptin; Mon.: Betanol; Neth.: Beta-Ophtiole; prompt but of longer duration than that of acetazolamide, Philipp.: Beta-Ophtiole; Pol.: Betamann; Port.: Beta-Ophtiolet; Physostigmine Sulfate {BANMJ lasting for 10 to 18 hours. S.Afr. : Beta-Ophtiole; Singapore: Beta-Ophtiole; Turk.: Turop­ The diuretic activity of methazolamide is less tin; USA: OptiPranolol. pronounced than that of acetazolamide. Multi-ingredient Preparations. Austria: Betacarpin; Belg.: Nor­ moglaucont; China: Normoglaucon (ll:E-�lt);Ger_; Normoglau­ Adverse Effects and Precautions con; Gr.: Beta Opthiole; Ripix; Neth.: Normoglaucont; PoL Normoglaucon; Port.: Normoglaucont. As for Acetazolamide, p. 2002.1. Pharmacopoeial Preparations Hypersensitivity. Cholestatic hepatitis with jaundice, rash, BP 2014: Metipranolol Eye Drops. and subsequent pure red cell aplasia was associated with

The symbol t denotes a preparation no longer actively marketed The symbol ® denotes a substance whose use may be restricted in certain sports (see p. viii)