286 Antibacterials

(Целестодерм-В с Гарамицином); Dexa-Gentamicin (Декса- Flodermol; Fludronef; Intradermo Cort Ant Fung†; Midacina; Oftalmowell; Гентамицин); Triderm (Тридерм); S.Afr.: Celestoderm-V with Garamy- Spectrocin†; Tivitis; Trigon Topico; Swed.: Bafucin; Switz.: Angidine; My- (BAN, USAN, rINN) cin†; Diprogenta; Garasone†; Palacos R with Garamycin; Quadriderm; Sep- colog N; Mycolog†; Neosporin; Sofradex; Topsym polyvalent; Tyrothricine N topal; Singapore: B-Tasone-G; Beprogent; Celestoderm-V with Garamy- + Gramicidine; Thai.: Dermacombin; Kenacomb; Neosporin†; Opsacin†; -Formimidoyl Thienamycin; Imipemide; Imipeneemi; Imipénem; cin†; Combiderm; Conazole; Dexamytrex; Diprogenta; Garasone; Polyoph; Sofradex; Topifram; Xanalin; Turk.: Neosporin; UAE: Panderm; Imipenem monohydrát; Imipenemas; Imipenemum; Imipene- Gentriderm; Gentrisone; Infectoflam; Modaderm; Neoderm; Quadri- UK: Graneodin†; Neosporin; Sofradex; Tri-Adcortyl; USA: Neosporin; mum Monohydricum; MK-787; MK-0787. (5R,6S)-6-[(R)-1-Hy- derm†; Refobacin Bone Cement R; Refobacin-Palacos R†; Septopal†; Tri- Ocu-Spor-G; Ocutricin; Polymycin; Venez.: Kenacomb. Micon; Triderm; Voltamicin†; Spain: Celestoderm Gentamicina; Cuatro- droxyethyl]-3-(2-iminomethylaminoethylthio)-7-oxo-1-azabicyc- derm; Diprogenta; Epitelizante; Flugen; Flutenal Gentamicina; Gentadexa; lo[3.2.0]hept-2-ene-2-carboxylic acid monohydrate. Interderm; Novoter Gentamicina; Swed.: Celeston valerat med gentamicin; Имипенем Septopal†; Switz.: Diprogenta; Indobiotic†; Infectoflam; Ophtasone; Qua- C H N O S,H O = 317.4. driderm; Septopal; Triderm; Voltamicin; Thai.: Beprogent; Beprogenta; S (rINN) 12 17 3 4 2 Dexamytrex; Diprogenta†; Genquin; Gental-F; Infectoflam; Pred Oph; Re- CAS — 64221-86-9 (anhydrous imipenem); 74431-23-5 fobacin-Palacos R; Septopal; Turk.: Indobiotic; UK: Collatamp EG; Gen- Gramicidin C; Gramicidina S; Gramicidine S; Gramicidinum S; So- (imipenem monohydrate). tisone HC; Palacos LV with Gentamicin; Palacos R with Gentamicin; Sep- viet Gramicidin. topal; Vipsogal; USA: Pred G; Venez.: Betaderm con Gentamicina; Description. Imipenem is the N-formimidoyl derivative of Celestoderm con Gentalyn; Diprogenta; Garabet; Garasone; Gentidexa; Gentisor†; Propiogenta†; Quadriderm; Triderm; Tridetarmon. Грамицидин C thienamycin, an produced by Streptomyces cattleya. C H N O = 1141.4. Pharmacopoeias. In Eur. (see p.vii), Jpn, and US. 60 92 12 10 Ph. Eur. 6.2 (Imipenem). A white, almost white, or pale yellow CAS — 113-73-5. powder. Sparingly soluble in water; slightly soluble in methyl al- Gramicidin (BAN, rINN) cohol. A 0.5% solution in water has a pH of 4.5 to 7.0. Store in Gramicidin D; Gramicidin (Dubos); Gramicidina; Gramicidinas; airtight containers at a temperature of 2° to 8°. Gramicidine; Gramicidinum; Gramisidiini; Gramisidin. Val Orn Leu D-Phe Pro USP 31 (Imipenem). A white to tan-coloured crystalline pow- Грамицидин der. Sparingly soluble in water; slightly soluble in methyl alco- CAS — 1405-97-6. hol. Store at a temperature not exceeding 8°. ATC — R02AB30. Pro D-Phe ValOrnLeu Incompatibility and stability. Imipenem is unstable at alka- ATC Vet — QR02AB30. line or acidic pH and the commercially available injection of im- Profile ipenem with sodium for intravenous use is buffered to provide, when reconstituted, a solution with pH 6.5 to 7.5. Li- O Gramicidin S is an antibacterial polypeptide, produced by Bacil- censed product information advises against mixing with other X Gly -Ala -Leu -Ala -Val -Val -Val -Trp lus brevis, and has similar properties to (p.358). It is antibacterials. unsuitable for systemic use and is used topically for the local H OH -Leu Y -Leu -Trp -Leu -Trp N treatment of susceptible infections and as lozenges for infections References. H of the mouth and throat. The hydrochloride is used similarly. 1. Bigley FP, et al. Compatibility of imipenem-cilastatin sodium with commonly used intravenous solutions. Am J Hosp Pharm Preparations 1986; 43: 2803–9. Gramicidin X Y Mol. Formula 2. Smith GB, et al. Stability and kinetics of degradation of imipen- A1 -Val -Trp CHNO Proprietary Preparations (details are given in Part 3) em in aqueous solution. J Pharm Sci 1990; 79: 732–40. A2 -Ile -Trp CHNO Rus.: Grammidin. Adverse Effects B1 -Val -Phe CHNO Multi-ingredient: Indon.: FG Ointment; FG Troches. Imipenem is always given with the inhibitor C1 -Val -Tyr CHNO cilastatin and thus clinical experience relates to the C2 -Ile -Tyr CHNO combination. Halquinol (BAN) Adverse effects with imipenem-cilastatin are similar in NOTE. The name gramicidin was formerly applied to tyrothricin. Chlorhydroxyquinoline; Chlorquinol; Halquinols (USAN); SQ- general to those with other beta lactams (see Ben- Pharmacopoeias. In Eur. (see p.vii), Jpn, and US. 16401. A mixture of the chlorinated products of quinolin-8-ol zylpenicillin, p.213, and , p.219). Hypersensi- Ph. Eur. 6.2 (Gramicidin). It consists of a family of antimicrobial tivity reactions such as skin rashes, urticaria, eosi- linear polypeptides usually obtained by extraction from ty- containing 57 to 74% of 5,7-dichloroquinolin-8-ol (chloroxine, rothricin, the complex isolated from the fermentation broth of p.242), 23 to 40% of 5-chloroquinolin-8-ol (cloxiquine, p.530), nophilia, fever, and, rarely, anaphylaxis may occur. Bacillus brevis. The main component is gramicidin A1, together and not more than 4% of 7-chloroquinolin-8-ol. Gastrointestinal effects include nausea, vomiting, diar- with gramicidins A2, B1, C1, and C2 in particular. The potency CAS — 8067-69-4. rhoea, tooth or tongue discoloration, and altered taste. is not less than 900 units/mg calculated with reference to the Superinfection with non-susceptible organisms such as dried substance. A white or almost white, slightly hygroscopic, Profile Enterococcus faecium, strains of Pseudomonas aeru- crystalline powder. Practically insoluble in water; sparingly sol- Halquinol is a halogenated hydroxyquinoline with properties uble in alcohol; soluble in methyl alcohol. Store in airtight con- similar to those of clioquinol (p.254). It is used topically in ginosa with acquired resistance, and Candida may also tainers. Protect from light. infected skin conditions. occur. Pseudomembranous colitis may develop. Ery- USP 31 (Gramicidin). An antibacterial substance produced by thema multiforme, exfoliative dermatitis, Stevens- Preparations the growth of Bacillus brevis (Bacillaceae); it may be obtained Johnson syndrome, and toxic epidermal necrolysis from tyrothricin. It has a potency of not less than Proprietary Preparations (details are given in Part 3) have been reported rarely. Increases in liver 900 micrograms of gramicidin per mg, calculated on the dried UK: Valpeda. basis. A white or practically white, odourless, crystalline, pow- and abnormalities in haematological parameters, in- der. Insoluble in water; soluble in alcohol. Store in airtight con- Multi-ingredient: Denm.: Kenacutan; Norw.: Kenacutan; Swed.: Kena- cluding a positive Coombs’ test, have been noted. tainers. cutan. Local reactions such as pain or thrombophlebitis may Profile occur after injection. Gramicidin has properties similar to those of tyrothricin (p.358) Seizures or convulsions have been reported with imi- and is too toxic to be given systemically. It is used topically for Ibafloxacin (BAN, USAN, rINN) the local treatment of susceptible infections usually with other -cilastatin, particularly in patients with a history antibacterials such as neomycin and B, and often Ibafloksasiini; Ibafloxacine; Ibafloxacino; Ibafloxacinum; R-835; S- of CNS lesions and/or poor renal function, but some- with a corticosteroid as well. 25930. 9-Fluoro-6,7-dihydro-5,8-dimethyl-1-oxo- 1H,5H-ben- times in those without predisposing factors for seizures Preparations zo[ij]quinolizine-2-carboxylic acid. given recommended doses. Mental disturbances and USP 31: Neomycin and Sulfates and Gramicidin Cream; Ne- Ибафлоксацин confusion have also been reported. omycin and Polymyxin B Sulfates and Gramicidin Ophthalmic Solution; Ne- Cilastatin has protected against the nephrotoxicity seen omycin and Polymyxin B Sulfates, Gramicidin, and Hydrocortisone Acetate C H FNO = 275.3. Cream; Neomycin Sulfate and Gramicidin Ointment; Nystatin, Neomycin 15 14 3 with high doses of imipenem given experimentally to Sulfate, Gramicidin, and Triamcinolone Acetonide Cream; Nystatin, Neo- CAS — 91618-36-9. mycin Sulfate, Gramicidin, and Triamcinolone Acetonide Ointment. animals. A harmless reddish coloration of urine has ATC Vet — QJ01MA96. Proprietary Preparations (details are given in Part 3) been observed in children. Multi-ingredient: Arg.: Antibiocort†; Aseptobron N; Biotaer Nasal; Bu- Effects on the nervous system. References. coangin N; Caext; Carnot Colutorio; Desenfriol Caramelos†; Gargaletas; 1. Eng RH, et al. Seizure propensity with imipenem. Arch Intern Gramibiotic†; Graneodin; Graneodin N; Kenacomb; Nasomicina; Neo Col- O tirot; Neo Pelvicillin; Pantometil; Proetztotal; Austral.: Kenacomb; Ne- Med 1989; 149: 1881–3. osporin; Otocomb Otic; Otodex; Sofradex; Soframycin; Austria: Mycosta- 2. Brown RB, et al. Seizure propensity with imipenem. Arch Intern tin V; Topsym polyvalent; Volon A antibiotikahaltig; Belg.: Mycolog; F COOH Med 1990; 150: 1551. Polyspectran Gramicidine; Braz.: Fonergin; Londerm-N; Mud; Neolon-D; 3. Job ML, Dretler RH. Seizure activity with imipenem therapy: Omcilon A M; Onciplus; Canad.: Antibiotic Cream†; Kenacomb†; Ne- incidence and risk factors. DICP Ann Pharmacother 1990; 24: osporin; Opticort; Optimyxin; Optimyxin Plus; Polycidin†; Polysporin; 467–9. Polysporin Complete Antibiotic; Polysporin For Kids; Polysporin Plus Pain 4. Leo RJ, Ballow CH. Seizure activity associated with imipenem Relief; Polysporin Triple Antibiotic; Polytopic; ratio-Triacomb; Sofracort; Sof- H3C N use: clinical case reports and review of the literature. DICP Ann ramycin; Triacomb†; Viaderm-KC; Chile: Grifoftal†; Oftabiotico; Cz.: Sof- Pharmacother 1991; 25: 351–4. radex†; Denm.: Kenalog Comp med Mycostatin; Sofradex; Fin.: Bafucin; 5. Duque A, et al. Vertigo caused by intravenous imipenem/cilasta- Polysporin; Sofradex; Ger.: Polyspectran; Gr.: Kenacomb; Neo-Priphen; CH tin. DICP Ann Pharmacother 1991; 25: 1009. Hong Kong: Kenacomb; Neosporin; Polyoph; Sofradex; Triacomb; Hung.: 3 6. Lucena M, et al. Imipenem/cilastatin-associated hiccups. Ann Polyspor ; India: Kenacomb; Kenalog-S; Neosporin; Sofracort; Indon.: Ble- H Pharmacother 1992; 26: 1459. cidex; Isotic Enpigi; Neosyd; Sofradex; Irl.: Graneodin; Kenacomb; Ne- 7. Norrby SR. Neurotoxicity of antibacterials. Drug osporin†; Sofradex; Soframycin†; Israel: Dermacombin; Kenacomb†; Ital.: Safety 1996; 15: 87–90. Eta Biocortilen VC; Vasosterone Antibiotico; Malaysia: Kenacomb; Pocin Profile G; Sofradex; Mex.: Biotarson N; Biotarson O; Kenacomb; Neosporin; Ibafloxacin is a fluoroquinolone antibacterial that is used in vet- Hypersensitivity. A retrospective analysis1 involving a total of Nicobio†; Polixin; Poly-Micron; Septilisin; Sulned; Neth.: Mycolog; Polyspec- erinary medicine for the treatment of susceptible infections in 211 patients appeared to show that those with a history of report- tran G†; Sofradex; Norw.: Sofradex; NZ: Kenacomb; Sofradex; Soframycin; Viaderm-KC; Philipp.: Kenacomb; Lidex NGN; Neosporin; Novasorin; cats and dogs. ed or documented allergy had an 11% incidence of hy- Pol.: Dicortineff; Triacomb; Port.: Dropcina; Kenacomb; S.Afr.: Kena- persensitivity reactions when treated with a carbapenem antibac- comb; Neosporin†; Sofradex; Singapore: Kenacomb†; Sofradex; Spain: terial compared with 2.7% for those without such a history of