Spain: Diformiltridnat; Hongosant; Xylonor; Switz.: Lemocin; thing Gel; Difflam Anti-inflammatory Lozenges (with Antibac Chlorhexidine Gluconate (BANM. USAN, riNNMJ Mebu; Septivon; Turexan Capillat; Venez.: Kertyol. terial); Difflam Anti-Inflammatory Lozenges (with cough sup pressant); Difflam Mouth Gel; Orregel; Pharynx; Mex. : Ch:lorneksidirio digliu!<6nato iirpaf�s; Chlorhexidin-,digluko Cepacaina; Mentalgina; Trociletas B; Neth.: Agre-Golat; Norw.: nar; Chlprhexfdine Di�ty.conate; (:h(orhexidili<'J, diqiuconate Cetylpyridinium Chloride (BAN. r/NNJ Asellit; NZ: Cepacaine; Cepacol Anaesthetict; Cepacol Cough de; Chlorhexidine, Gl'lconate -d� Chlorhexidfni dkJI1Konas; Discs; Cepacol Sore Throat; Difflam Anti-inflammatory Antibac Chlorhexidini D(giuconatis . Solutio; Chlefnexidi!\i Cilll!:tmas; Cetiipiridinio chloridas; Cetilpiridinio,. cloruro de; Cetilpir terial Lozenges; Difflam Cough; Difflam Mouth Gel; Duro-Tuss Chloroheksydyny diglukonianu - \roztw6r; Oorhexidina) idin•um-klorid; Cetylpyridlnli Chloridum; Cety!pyridinii Lozenges; Philipp.: Difflam Orange; Kene; Xylorinse; Pol. : · gh.rconato de; Glu�_o!1ato de cforht>xidina; l
The symbol t denotes a preparation no longer actively marketed 1 744 Disinfectants and Preservatives >w·•�·"'""""'-'"''�"�'"'"''"...-.'"''""'''''"''-�"""'-"'"-"' .....,__ "'" '�""--"''-"""'""'�""'-'•'��-,,,,v•"''""'"-�·''*·'""'·�""'"""�--�-�------'•"."'d'<".,..""""'--"'"'___ ,....,_,,"""""'"''""k".'"""'"''�""'"'"�-·=-..,---..,--"'-'="'--q-.,, "'""-.,-"-...... ,'-"""�""""'"'""'"""""'''______.,._.....,..,...... ,...... ,.,.�..,�'"
chlorides, dtrates, nitrates, phosphates, and sulfates, form toms occurred within 1 to 7 weeks (mean 3 weeks); available at: http://circ.ahajournals.org/cgi/reprlnt/ Il6/l5/l736.pdf ing salts of low solubility which may precipitate out of patients noted a reduction of pain, photophobia and lid {accessed 23/06/IO) 3. NICE. Prophylaxis against infective endocarditis: antimicrobial prophy solution. At dilutions of 0.01% or more, these salts are oedema after 3 weeks of treatment. No drug toxicity was laxis against infective endocarditis in adults and children undergoing generally soluble. Insoluble salts may form in hard water. noted in any of the patients. However, concern has been interventional procedures (issued March 2008). Available at: http:// Chlorhexidine salts are inactivated by cork. expressed over the possible toxicity of chlorhexidine at www.nice.org.uk/nicemedia/pdf/CG64NICEguidance.pdf (accessed References to incompatibilities of chlorhexidine with this concentration on the cornea (see Adverse Effects and 23/06/IO) suspending agents and insoluble solids 1·3 Treatment, p. 1745.1). I. McCarthy TJ. The influence of insoluble powders on preservatives in Chlorhexidine is also an effective disinfectant against Mouth disorders. Chlorhexidine mouthwashes, sprays, J Mond Phann solution. 1969; 12: 321-8. Acanthamoeba cysts and most bacteria found in contact lens and gels are used to prevent accumulation of dental 2. Yousef RT, et al. Effect of some pharmaceutical materials on the storage cases. 2 bactericidal activities of preservatives. Can J Phann Sd 1973; 8: 54-6. plaque (see Mouth Infections, p. 192.3). Early studies1•4 Chlorhexidine has also been used to treat skin lesions 3. McCarthy TJ,My burgh JA. The effect of tragacanth gel on preservative generally showed chlorhexidine mouthwash 0.1 to 0.2% activity. Pharm Weekbl l974; 109: 265-8. associated with disseminated Acanthamoeba infection3 as an used 2 or 3 times daily to be effective in reducing plaque adjunct to systemic therapy (see p. 920.1). accumulation and gingivitis and provided limited evidence Stability. Chlorhexidine and its salts are stable at normal I. Seal D, et a!. Successful medical therapy of Acanthamoeba keratitis with of efficacy in preventing caries in permanent teeth of chil Eye storage temperatures but when heated may decompose topical chlorhexidine and propamidine. 1996; 10: 413-21. dren and adolescents. A retrospective review5 of 22 con BMJ with the production of trace amounts of 4-chloroaniline. 2. Seal DV. Acanthamoeba keratitis. 1994; 308: 1116-17. 3. Slater CA, et al. Brief report: successful treatment of disseminated trolled studies of chlorhexidine for caries prevention, Chlorhexidine hydrochloride is less readily decomposed Acanthamoeba infection in an immunocompromised patient. N Engl J found the evidence inconclusive in schoolchildren and than chlorhexidine acetate and may be heated at 150 Med 1994; 331: 85-7. adolescents with active caries and regular fluoride expo degrees for I hour without appreciable production of 4- sure; there was also no good evidence that it arrested root chloroaniline. Aqueous solutions of chlorhexidine salts Contraception. Bisbiguanides of the chlorhexidine type caries in patients with dry mouth and in frail elderly sub decompose with the formation of trace amounts of 4- are reported to have the ability to diffuse into cervical jects. However, chlorhexidine varnishes showed a preven chloroaniline. This decomposition is increased by heating mucus and render it impenetrable to sperm at concentra tative effect for fissure caries compared with no treatment and alkaline pH. tions as low as 1 mg/mL 1 Higher concentrations of chlor in children with low fluoride exposure. Other studies have hexidine structurally modify the mucus, producing a bar shown that chlorhexidine reduces gingivitis by 60 to 90% Uses and Administration rier to both the entry of sperm and chlorhexidine. The but its use is limited by its unpleasant taste and staining potency1 of chlorhexidine in inhibiting sperm motility in properties; special circumstances in which chlorhexidine is Chlorhexidine is a bisbiguanide antiseptic and disinfectant vitro is identical to that of nonoxinol 9, but unlike spermi helpful include management of acute gingivitis, control of that is bactericidal or bacteriostatic against a wide range of cides containing nonoxinol 9, which tend to trickle out, periodontal involvement in immunocompromised Gram-positive and Gram-negative bacteria. It is more the clearance of chlorhexidine from the vagina is delayed.2 patients, and promotion of healing after periodontal treat effective against Gram-positive than Gram-negative Chlorhexidine also has potential for reducing transmission ment.6 bacteria, and some species of Pseudomonas and Proteus have of HIV infection as it does not disrupt the vaginal epithe Chlorhexidine gluconate may be useful in controlling low susceptibility. It is relatively ineffective against lium and has activity in vitro against the HIV virus in low secondary bacterial infections of aphthous ulcers (see mycobacteria. Chlorhexidine inhibits some viruses and is concentrations. 2 Mouth Ulceration, p. 1811.2). Local application of chlor active against some fungi. It is inactive against bacterial For a review of contraception, including the view that hexidine has been reported to reduce the incidence7 and spores at room temperature. Chlorhexidine is most active at spermicides are not a particularly effective method unless duration and severity8 of recurrent ulcers, although one a neutral or slightly acid pH. Combinations of chlorhexidine used with other means of contraception, see p. 2232.3. study showed no benefit compared with placebo. 9 However, with cetrimide (p. 1742.1) or in alcoholic solution are used 0 I. Pearson RM. Update on vaginal spermicides. Pharm J 1985; 234: 686-7. a retrospective review1 of 7 studies comparing chlorhexi to enhance efficacy. 2. Anonymous. Multipurpose spermicides. Lancet 1992; 340: 2ll-l3. dine with placebo or no treatment found no evidence that Chlorhe:xidine is formulated as lotions, washes, and chlorhexidine prevents oral mucositis in patients receiving creams for disinfection and cleansing of skin and wounds Disinfection. Viable bacterial counts on the hands were cancer treatment. (p. 1690.1), and as oral gels, sprays, and mouthwashes for reduced by a mean of 97.9% by the application of chlor Chlorhexidine may be a useful adjunct to antifungal mouth infections including candidiasis and to reduce dental hexidine gluconate 0.5% in alcohol 95%.1 The reduction treatment of oral candidiasis11 (p. 564.1). plaque accumulation. It has also been used with neomycin was not so substantial with a 0.5% chlorhexidine aqueous For the need for a delay when using chlorhexidine with to eliminate nasal carriage of staphylococci (p. 208.2) and solution (65.1% reduction in bacterial count) or a 4% other oral hygiene preparations, see under Precautions, for disinfection of some contact lenses (but see Precautions, detergent solution (86.7%). Hand disinfection with chlor p. 1745.3. p. 1745.3). It has been suggested for use with propamidine hexidine gluconate 4% appeared to be more effective than L Fkitra L, et al. A 4-month study on the effect of chlorhexidine mouth isetionate for the treatment of Acanthamoeba keratitis and the use of isopropyl alcobol 60% and soap in preventing washes on 50 soldiers. Scand J Dent Res 1972; 80: 10-17. in spermicides to prevent transmission of HIV infection (see nosocomial infections in a study conducted in intensive 2. O'Neil TCA, Figures KH. The effects of chlorhexidine and mechanical IDV Infection Prophylaxis, p. 959.1). methods of plaque control on the recurrence of gingival hyperplasia in care units but this may have been partly due to better Br Dent J 152: For pre-operative skin disinfection and hand-washing, young patients taking phenytoin. 1982; 130--3. compliance with hand-washing instructions when using 3. de la Rosa M, et al. The use of chlorhexidine in the management of chlorhexidine is used as a 0.5% solution of the acetate or chlorhexidine 2 In another study, 3 pre-operative total body gingivitis in children. J Periodontol 1988; 59: 387-9. gluconate in alcohol (70%) or as a 2 or 4% detergent bathing with a 4% detergent did not decrease the risk of 4. O'Neil TCA. The use of chlorhexidine mouthwash in the control of gingival inflammation. Br Dent J 1976; 141: 276-80. solution of the gluconate. For disinfection of wounds, bums, wound infection in patients compared with bathing in or other skin damage or disorders chlorhexidine is used as a 5. Twetman S. Antimicrobials in future caries control: a review with special detergent alone. reference to chlorhexidine treatment. Caries Res 2004; 38: 223-9. 0.05% aqueous solution of the acetate or gluconate, as a Chlorhexidine I% nasal cream failed to control an 6. Greene JC, et a!. Preventive dentistry II: periodontal diseases, tulle dressing impregnated with chlorhexidine acetate epidemic of meticillin-resistant Staphylococcus aureus in a malocclusion, trauma, and oral cancer. lAMA 1990; 263: 421-5. 0.5%, or as a cream or powder containing chlorhexidine 7. Hunter L, Addy M. Chlorhexidine gluconate mouthwash in the neurosurgical ward4 and handwashing with chlorhexidine Br Dent J acetate or gluconate 1%. Preparations containing chlor management of minor aphthous ulceration. 1987; 162: 106-IO. soap failed to control an outbreak of infection with Staph. 8. Addy M, et a!. Management of recurrent aphthous ulceration: a trial of hexidine acetate or gluconate 0.015% and cetrimide 0. 15% aureus resistant to meticillin and gentamicin in a neonatal chlorhexidine gluconate gel. Br Dent J 1976; 141: 118-20. are also used for cleansing and disinfection of skin and intensive care unit. 5 The organisms were subsequently 9. Matthews RW, et al. Clinical evaluation of benzydamine, chlorhexidine, wounds. In obstetrics, chlorhexidine gluconate is used as a and placebo mouthwashes in the management of recurrent aphthous eradicated by the use of nasal mupirocin and hexachlor Oral Surg Oral Med Oral Pathol l987; 0.05% aqueous solution or a 1% cream. The cream is also stomatitis. 63: 189-91. ophene handwashing, respectively. 10. Worthington et al. Interventions for preventing oral mucositis for used as a barrier against bacterial hand infection. HV, I. Lowbury EJL, et al. Preoperative disinfection of surgeons' hands: use of patients with cancer receiving treatment. Available in The Cochrane Chlorhexidine gluconate is used in a I% dental gel, 0.2% alcoholic solutions and effects of gloves on skin flora. BMJ 1974; 4: 369- Database of Systematic Reviews; Issue 4. Chichester: John Wiley; 2007 oral spray, and 0.1 to 0.2% mouthwash for the prevention 72. (accessed 27/08/08). of plaque and the prevention and treatment of gingivitis and 2. Doebbeling BN, et al. Comparative efficacy of alternative hand-washing 1 L WHO. WHO model prescribing information: drugs used in skin diseases. N Eng! J Geneva: WHO, 1997. in the treatment of oral candidiasis. A slow-release agents in reducing nosocomial infections in intensive care units. Med 1992; 327: 88-93. formulation containing 2.5 mg of chlorhexidine gluconate 3. The European Working Party on Control of Hospital Infections. A for insertion into periodontal pockets is also available. comparison of the effects of preoperative whole-body bathing with Obstetric use. Disinfection of the birth canal with chlor A 0.02% solution may be used as a bladder irrigation in detergent alone and with detergent containing chlorhexidine gluconate bexidine gluconate 0.05 to 0.4% during labour has been J Hosp Infect some urinary-tract infections. A gel containing 0.25% on the frequency of wound infections after dean surgery. 1988; 11: 310-20. investigated as a method for reducing mother-to-child chlorhexidine gluconate solution and lidocaine hydro 4. Duckworth G. New method for typing Staphylococcus aureus resistant transmission of infections, including early-onset group B chloride has been used in catheterisation and cystoscopy. to methicillin. BMJ 1986; 293: 885. streptococcal infection and HIV. 1-6 Studies have shown For the emergency disinfection of clean instruments, a 2- 5. Reboli AC, et al. Epidemic methicillin-gentamicin-resistant Staphylo that it has not reduced perinatal transmission of HIV Am J Dis Child minute immersion in chlorhexidine acetate or gluconate coccus au reus in a neonatal intensive care unit. 1989; 143: 34-9. except when membranes were ruptured for more than 4 0.5% in alcohol (70%) is used; for the storage and hours before delivery1 or if used before the membranes disinfection of clean instruments a 30-minute immersion in /NJECnON SITE AND CATHETER CARE. See p. 1732.1. rupture and at higher concentrations.4 A systematic a 0.05% aqueous solution containing 0.1% sodium nitrite review of 5 studies-5 to determine the efficacy of chlorhexi to inhibit metal corrosion is used. Endocarditis. Some guidelines1 have recommended chlor dine vaginal disinfection for preventing early-onset group As an antimicrobial preservative, chlorhexidine is used at hexidine mouthwash 0.2%, held in the mouth for I min· B streptococcal infection concluded that, although there a concentration of 0.01% of the acetate or gluconate in eye ute, as an adjunct to antimicrobials for the prophylaxis of was a statistically significant reduction in colonisation drops. Solutions containing 0.002 to 0.006% of chlorhexi endocarditis in at-risk patients undergoing dental proce there was no significant reduction in early-onset infection, dine gluconate have also been used for disinfection of dures; however, subsequent guidelines23 consider topical morbidity or mortality. Comparable results have been hydrophilic contact lenses. antiseptic rinses to be ineffective for such use and recom reported with the use of chlorhexidine gluconate I% mend that they should not be used. The protective cover obstetric cream at each examination during labour. 3 Simi Acanthamoeba infections. As discussed on p. 919.3, the required for such patients is discussed on p. 179.2. larly, a large randomised controlled study assessing intra optimal antiamoebic therapy for Acanthamoeba keratitis 1. Gould FK et al. Guidelines fur the prevention of endocarditis: report of partum and neonatal use of chlorhexidine 0.5%, con has yet to be determined. Propamidine isetionate is com the Working Party of the British Society for Antimicrobial Chemother cluded there was no effect on neonatal sepsis,' although it M J Antimicrob Chemother monly used, usually in combinations including a bigua apy. 2006; 57: 1035--42. Also available at: http:// has been argued that this simple intervention should not jac.oxfordjoumals.orgfcgi/reprint/dkll2lvl.pdf (accessed 23/06/l 0) nide. A multicentre study1 evaluated the efficacy of a com 2. Wilson W, et al. Prevention of infective endocarditis: guidelines from the be abandoned 8 bination of topical chlorhexidine 0.02% and propmnidine American Hean Association: a guideline from the American Heart A systematic review of 3 studies6 to determine the 0. 1% in 12 contact lens-wearing patients with confirmed Association Rheumatic Fever, Endocarditis, and Kawasaki Disease efficacy of chlorhexidine vaginal disinfection for preventing Acanthamoeba keratitis. Patients were treated for between Committee, Council on Cardiovascular Disease in the Young, and the perinatal transmission of infections other than group B Council on Clinical Cardiology, Council on Cardiovascular Surgery and 2 to 6 months and resolution of signs occurred gradually Anesthesia, and the Quality of Care and Outcomes Research streptococcal infection and HIV found no evidence to over 5 to 28 weeks (mean II weeks). Resolution of symp- Interdisciplinary Working Group. Circulation 2007; 116: 1736-54. Also support its use. However, a study2 conducted in Malawi
All cross-references refer to entries in Volume A Chlorhexidine 1745
reported a reduction in neonatal morbidity and mortality operative preparation of facial skin.1 Severe corneal normal one week later. After one month the serum from other neonatal infections. endothelium damage occurred in a further 3 patients2 aspartate aminotransferase was returning to normal while
1. Biggar RJ, et a!. Perinatal intervention trial in Africa: effect of a birth when chlorhexidine was inadvertently used as an intra the serum alanine aminotransferase was still 3 times canal cleansing intervention to prevent HIV transmission. Lancet 1996; ocular irrigating solution and 2 of the patients subse normal. Six months after ingestion the aminotransferase 347: 1647-50. quently required penetrating keratoplasty. Other adverse levels were normal. A liver biopsy performed soon after the 2. Taha TE, et al. Effect of cleansing the birth canal with antiseptic solution on maternal and newborn morbidity and mortality in Malawi: clinical effects included pronounced iris atrophy, anterior chamber peak in aminotransferase levels showed diffuse fatty trial. BMJ 1997; 315: 216-20. flattening, and a retrocorneal membrane; one patient degeneration and lobular hepatitis suggesting that chlor 3. Lindemann R. et a!. Vaginal chlorhexidine disinfection during labour. developed raised intra-ocular pressure. In another case hexidine was absorbed from the gastrointestinal tract in a Lancet 1992; 340: 792. progressive ulcerative keratitis and almost total loss of the concentration high enough to produce liver necrosis. An 4. Gaillard P, et al. Vaginal lavage with chlorhexidine during labour to 3 � reduce mother-to-child HIV transmission: clinical trial in Mombasa, corneal epithelium was reported after use of chlorhexi 80-year-old woman had spontaneous vomiting and aspira Kenya. AIDS 2001; 15: 389-96. dine gluconate 0.02% and propamidine 0.1% eye drops tion followed by acute respiratory distress syndrome within 5. Stade B, et al. Vaginal chlorhexidine during labour to prevent early for 8 weeks for Acanthamoeba keratitis. In 2 patients4 trea 5 hours of accidental ingestion of 200 mL of a chlorhexidine onset neonatal group B streptococcal infection. Available in The ted similarly for 4 to 6 months, deep marginal ulceration gluconate 5% solution. 6 Despite supportive treatment, the Cochrane Database of Systematic Reviews; Issue 3. Chichester: John Wiley; 2004 {accessed 06/041 10). of the cornea developed, in each case requiring a penetrat patient's condition continued to deteriorate and she 6. Lumbiganon P, et al. Vaginal chlorhexidine during labour for preventing ing graft; a mature cataract and an atrophic iris were seen developed shock and metabolic acidosis and died from maternal and neonatal infections {excluding group B streptococcal and in each patient after removal of the cornea. Due to the cardiac arrest 12 hours after ingestion. HIV) . Available in The Cochrane Database of Systematic Reviews; Issue similarity of both cases, it was suggested that these compli Accidental intravenous administration of 4mL of a 20% 4. Chichester: John Wiley; 2004 (accessed 06/04! 10). 7. Cutland CL, et al. PoPS Trial Team. Chlorhexidine maternal-vaginal and cations were caused by the drugs rather than by amoeba chlorhexidine gluconate solution in a 67-year-old man neonate body wipes in sepsis and vertical transrrussion of pathogenic induced inflammation. undergoing a colectomy resulted in the sudden develop bacteria in South Africa: a randomi�ed, controlled trial. Lancet 2009; 374: l. Tabor E, et at. Corneal damage due to eye contact with chlorhexidine ment of acute respiratory distress syndrome.7 Respiratory 1909-16. gluconate. lAMA 1989; 261: 557-8. failure progressed despite plasma exchange therapy over 3 8. Mullany LC, Biggar RJ. Vaginal and neonatal skin cleansing with 2. Anders N, Wollensak J. Inadvertent use of chlorhexidine instead of consecutive days. Vena-arterial extracorporeal membrane chlorhexidine. Lancet 2009; 374: 1873-5. balanced salt solution for intraocular irrigation. J Cataract Refract Surg 1997; 23: 959-62. oxygenation was started on the third day and after 72 hours Urinary catheter-related infection. Chlorhexidine solu 3. Murthy S, et al. Progressive ulcerative keratitis related to the use of improvement was noted and the patient subsequently tions have been used in the management of catheter topical chlorhexidine gluconate (0.02%). Cornea 2002; 21: 237-9. recovered completely. 4. Ehlers N, Hjortdal J. Are cataract and iris atrophy toxic complications of I. Quinn MW, Bini RM. Bradycardia associated with chlorhexidine spray. related bladder infections and for urinary catheter mainte Acta Ophthalmol Scand medical treatment of acanthamoeba keratitis? Arch Dis Child 1989; 64: 892-3. nance. Twice-daily bladder irrigation with chlorhexidine 2004; 82: 228-3 I. 2. Emerson D, Pierce C. A case of a single ingestion of 4% Hibiclens. Vet acetate 0.02% did not produce a reduction in urinary bac Hum Toxicol 1988; 30: 583. terial counts in geriatric patients with indwelling catheters, Effects on thenose. Temporary hyposmia (reduced sense 3. Chan TYK. Poisoning due to Savlon {cetrimide) liquid. Hum Exp Toxicol and there was a tendency for overgrowth of Proteus spp. in of smell) in some patients after transsphenoidal pituitary 1994; 13: 681-2. . patients given chlorhexidine.1 In patients undergoing adenoma operation was assumed to be caused by pre 4. Roche S, et a!. Chlorhexidine-induced gastritis. Postgrad Med J 1991; 67: 210-1 1. prostatectomy, intermittent pre-operative bladder irriga operative disinfection of the nasal cavity with chlorhexi 5. Massano G,et al. Striking aminotransferase rise after chlorhexidine self tion with chlorhexidine gluconate 0.05% reduced the dine gluconate solution.1 poisoning. Lancet 1982; i: 289. incidence of bacteraemia and severe wound infection, 1. Yamagishi M, et al. Impairment of olfactory epithelium treated with 6. Hirata K. Kurokawa A. Chlorhexidine gluconate ingestion resulting in Vet Hum Toxico/ 2002; 89-91. although urinary infections were eradicated in only 3 of chlorhexidine digluconate (Hibitane). Pract Oto/ 1985; 78: 399--409. fatal respiratory distress syndrome. 44: 7. Ishigami S, et a!. Intravenous chlorhexidine gluconate causing acute the 13 patients treated 2 respiratory distress syndrome. J Toxicol Clin Toxicol 200I; 39: 77-80. Addition of chlorhexidine to catheter drainage bags was Hypersensitivity. Both immediate and delayed hypersensi not shown to reduce the frequency of urinary infections, 3 tivity reactions have been reported after topical use of but infection rates were reduced by combining this chlorhexidine1 and from the use of chlorhexidine-contain- Precautions ing urethral lubricants. 2 However, the incidence is low technique with the use of a catheter lubricant containing 'l Since chlorhexidine is irritant it is recommended that it chlorhexidine, disinfection of the urethral meatus, and given the frequent use of chlorhexidine. Delayed hyper should not be used on the brain, meninges, middle ear, or aseptic nursing procedures • The use of lubricating gel sensitivity reactions such as contact dermatitis, fixed drug other sensitive tissues. Contact with the eye should be containing chlorhexidine did not reduce the risk of urinary eruptions, and photosensitivity reactions are more com avoided except for dilute solutions expressly for use in the tract infections associated with short-term catheterisation, 5 mon than immediate hypersensitivity reactions (acute eyes. Chlorhexidine may be adsorbed by some soft contact and in general external disinfection of the periurethral area urticaria, angioedema, and bronchospasm which may lenses and cause eye irritation, although it may be suitable alone does not seem to be of benefit in reducing the rate of progress to anaphylactic shock). u for use with others (see Contact Lens Care, p. 1730.2). catheter-related bacteriuria. 6• 7 Immediate hypersensitivity reactions have also occurred Syringes and needles that have been immersed in The treaunent of urinary-tract infections is discussed on with surgical disinfection. Signs appear 15 to 45 minutes chlorhexidine solutions should be thoroughly rinsed with p. 213.1. after the start of surgery and include hypotension, urticaria, sterile water or saline before use. l. Davies AJ,et at. Does instillation of chlorhexidine into the bladder of tachycardia, bronchospasm, and sometimes anaphylactic Aqueous solutions of chlorhexidine salts may be catheterized geriatric patients help reduce bacteriuria? J Hosp Infect 1987; shock, cardiovascular collapse, or cardiac arrest. 3.4 In 1998 susceptible to contamination with micro-organisms. To 9: 72-5. the FDA issued a public notice' warning of potential 2. AA et a!. reduce this risk, a sterilised preparation should be used or, Adesanya , The use of intermittent chlorhexidine bladder hypersensitivity reactions to chlorhexidine-impregnated irrigation in the prevention of post-prostatectomy infective complica where necessary, solutions must be freshly prepared at the tion<>. Int Urol Nephro/ 1993; 25: 359-67. intravenous catheters, topical antimicrobial skin dressings, recommended concentration and appropriate measures 3. Gillespie WA, et al. Does the addition of disinfectant to urine drainage and implanted antimicrobial surgical mesh, based on reports should be taken to prevent contamination during storage or Lancet 1983; 1037-9. bags prevent infection in catheterised patients? i: of adverse events that had occurred in the USA and other dilution. 4. Southampton Infection Control Team. Evaluation of aseptic techniques countries. and chlorhexidine on the rate of catheter-associated urinary-tract Aqueous solutions of chlorhexidine used for instrument Occupational asthma has been attributed to an alcoholic infection. Lancet I 982; i: 89-91. storage should contain sodium nitrite 0.1% to inhibit metal HA 5. Schi0tz . Antiseptic catheter gel and urinary tract infection after chlorhexidine spray 6 corrosion, and should be changed every 7 days. Commercial short-term postoperative catheterization in women. Arch Gynecol Obstet I. Krautheim AB, et a!. Chlorhexidine anaphylaxis: case report and review 1996; 258: 97-100. 5% concentrate contains a nonionic surfactant to prevent of the literature. Contact Dermatitis 2004; 50: I 13-16. 6. Webster J, et al. Water or antiseptic for periurethral cleaning before precipitation on dilution with hard water and is not suitable 2. Jayathillake A, et al. Allergy to chlorhexidine gluconate in urethral gel: urinary catheterization: a randomized controlled trial. Am J Infect Control report of four cases and review of the literature. Urology 2003; 61: 837iv- for use in body cavities or for disinfection of instruments 29: 2001; 389-94. 837vi. containing cemented glass components; dilutions of the 7. Koskeroglu N, et a!. The role of meatal disinfection in preventing 3. Beaudouin E, et al. Immediate hypersensitivity to chlorhexidine: 20% concentrate should be used for thls purpose. catheter-related bacteriuria in an intensive care unit: a pilot study in literature review. Allerg Immunol (Paris) 2004; 36: 123-6. Turkey. J Hosp Infect 2004; 56: 236-8. et al. 4. Chisholm DG, Intranasal chlorhexidine resulting in an anaphylactic Ralstonia pickettii (Burkholderia pickettii; circulatory arrest. BMJ 1997; 315: 785. Contamination. 5. FDA. FDA Public Health notice potential hypersensitivity reactions to Pseudomonas pickettii) septicaemia developed in 6 patients Adverse Effects and Treatment chlorhexidine-impregnated medical devices (issued II th March, 1998). after the use of aqueous chlorhexidine 0.05%, prepared Skin sensitivity to chlorhexidine has occasionally been Available at: http://www.fda.gov/McdicalDevices/Safety/ with contaminated twice-distilled water, for skin disinfec reported. Severe hypersensitivity reactions, including AlertsandNotices/PublicHealthNotiflcations/UCM062306 (accessed ll/05110) tion before venepuncture and it was considered that anaphylactic shock, have been reported rarely after topical 6. Wadawski ER, et al. Occupational asthma in nurses caused by unsterilised 0.05% solutions should not be used for such use of chlorhexidine. Strong solutions may cause irritation chlorhexidine and alcohol aerosols. BMJ I989; 298: 929-30. skin preparation. 1 Positive blood cultures of Burkho/deria of the conjunctiva and mucous membranes. The use of cepacia (Pseudomonas cepacia) were found in 2 patients after chlorhexidine dental gel and mouthwash has been Poisoning. Reports of adverse effects after ingestion of inappropriate use of a chlorhexidine handwash for the associated with reversible discoloration of the tongue, chlorhexidine salts include a neonate who developed mul same purpose 2 Further studies showed that the handwash teeth, and silicate or composite dental restorations. tiple episodes of cyanosis and bradycardia;' the infant's supported pseudomonal growth only when diluted.' Transient taste disturbances and a burning sensation of mother had sprayed chlorhexidine onto her breasts to pre 1. Kahan A, et al. Is chlorhexidine an essential drug? Lancet 1984; ii: 759- the tongue may occur on initial use. Oral desquamation and vent mastitis. In contrast an 89-year-old woman only had 60. occasional parotid gland swelling have been reported with mild giddiness, unusual laughter, and an increased appe 2. Gosden PE, Norman P. Pseudobacteraemia associated with contami Lancet 1985; 671-2. the mouthwash. If desquamation occurs, 50% dilution of tite after mistakenly drinking 30 mL of a solution contain nated skin cleansing agent. ii 3. Norman P, et a!. Pseudobacteraemia associated with contaminated skin the mouthwash with water and less vigorous rinsing may ing chlorhexidine gluconate 4% and isopropyl alcohol cleansing agent. Lancet 1986; i: 209. allow continued use. 4%.2 A review3 of 7 adult cases of deliberate ingestion of a The main consequence of ingestion is mucosal irritation commercially available mixture of cetrimide 3% and Neonates. Haemorrhagic skin necrosis associated with and systemic toxicity is rare due to minimal absorption from cblorhexidine gluconate 0.3%, concluded that symptoms umbilical artery catheterisation in a premature infant was the gastrointestinal tract (see Poisoning, below). Haemolysis were generally mild and included nausea, vomiting, sore attributed to damage by the alcohol from the use of chlor has been reported after accidental intravenous administra throat, and abdominal pain. There has also been a report hexidine 0.5% in spirit 70% as a disinfectant_! tion. Gastric lavage with demulcents has been suggested in of a patient who developed gastritis after ingesting a pre For reference to the percutaneous absorption of some licensed product information for treatment of acute operative skin preparation containing chlorhexidine chlorhexidine after topical use in neonates and infants, ingestion; however, other authorities recommend that the gluconate 4% when using it as a mouthwash.4 see under Pharmacokinetics, p. 1746.1. stomach should not be emptied as this may increase the risk Another person had much more serious effects after 1. Harpin V, Rutter N. Percutaneous alcohol absorption and skin necrosis of mucosal irritation. Small volumes of milk or water to drinking about 150mL of chlorhexidine gluconate solution, in a preterm infant. Arch Dis Child 1982; 57: 477-9. drink may be warranted. corresponding to about 30 g of the pure substance. 5 Besides pharyngeal oedema and necrotic oesophageal lesions, the Oral hygiene. Toothpastes may contain anionic surfac Effects on the eyes. Corneal damage was reported in 4 patient had aminotransferase concentrations that rose to 30 tants such as sodium laurilsulfate, which are incompatible patients after use of chlorhexidine gluconate for pre- times normal 5 days after ingestion and were still 8 times with chlorhexidine. In order that the antiplaque effect of 1 746 Disinfectants and Preservatives
chlorhexidine is not reduced, it has been recommended GynePro; Oradex; Mex. : Perioxidint; Neth.: Corsodyl; Dettol 77B:rso-5. that at least 30 minutes should be allowed to elapse Sterilon; Hibiscrub; Hibitanet; Hydrext; Irrisol; Lifo-Scrub; � - 4R7X!02fJ2 0 between teeth brushing and rinsing with oral chlorhexi Periochip; Urogliss�S; Norw.: Corsodyl; Hibiscrub; Hibitane; Description. Chlorine is a greenish-yellow gas with a dine preparations.1 Periochip; NZ: DP Hand Rubt; Hibitanet; Riotanet; Philipp.: Pol.: suffocating odour; commonly available as a pressurised 1. et al. Bactigras; GynePro; Orahex; Para-Tulle; Corsodyl; Septo Barkvoll P, Interaction between chlorhexidine cligluconate and liquid. sodium lauryl sulfate in vivo. J Clin Periodontol l989; 16: 593-5. fervext; Pori. : Alospray; Bexident; Cloraldint; Corsodyl; Dia lenst; Handscrub; Hibitane; Lifo-Scrubt; Periochip; Rus.: Ami Porphyria. The Drug Database for Acute Porphyria, com dent (AMH.IJ;eHT); Elgydium (3nhrH)l;HYM); Elugel (3morem,); (reKCHKOH); S.Afr. : Uses and Administration piled by the Norwegian Porphyria Centre (NAPOS) and Hexicon Bactigras; Corsodyl; D-Germt; Hex idint; Hibiscrubt; Hibitane; Oroseptt; Singapore: Baby Shield Chlorine is a disinfectant with a rapid potent brief the Porphyria Centre Sweden, classifies chlorhexidine as Plus; Chlorohex; Elgydium; EluDentalt; Elugel; Hexoscrub; bactericidal action. It is capable of killing most bacteria, and not porphyrinogenic; it may be used as a drug of first Obstetric Care; Periochipt; Pfizer Obstetric Lotiont; Trihexid; son1e fungi, yeasts, algae, viruses, and protozoa. It is slowly choice and no precautions are needed.1 Spain: Clorxil; Cristalcrom; Cristalmina; Curafilt; Cuvefilm; active against spores. I. The Drug Database for Acute Porphyria. Available at: http://www. Deratin; Hibimaxt; Hibiscrub; Menalmina; Nonnosept; Septi It is used for the treatment of water (p. 1731.3), but for drugs-porphyria.org (accessed 24110/ll) sant; Swed. : Corsodyl; Descutan; Hexident; Hibiscrub; Hibitane; most other purposes it is used in the form of hypochlorites, Periochip; Switz.: Atoseptal; Chlorhexamed; Corsodyl; Dento Washing precautions. Fabrics that have been in contact organic and inorganic chloramines, chlorinated hydantoins, hexin; DermaPlast Desinfect; Dosiseptinet; Elgydium; Hexame chlorinated isocyanurates, and similar oxidising compounds with chlorhexidine solution may develop a brown stain if dal; Hibidil; Hibiscrub; Hibitanet; Lifo-Scrub; Meridol Perio; capable of releasing chlorine. In the presence of water these bleached with a hypochlorite. A peroxide bleach may be Periochip; Plak Out; Thai.: B-Mouthwash; Bacard Antiseptic; compounds produce hypochlorous acid (HOC!) and hypo used instead. Bactigras; C-20; Chlorhex; Hexene; Hexide; Hexidine; Hibiscrubt; Hibitanet; Hydrex; Obitane; OR; Q-Bact; Turk. : chlorite ion ( OCI") and it is generally considered that the Cloder; Disinfectingt; Gargarex; Hibitanol; Klorheksol; Klorhex; lethal action on micro-organisms is due to chlorination of Pharmacokinetics Mediscrub; Oroheks; Superheks; UAE: Zordyl; UK: Acriflex; cell protein or enzyme systems by nonionised hypochlorous Chlorhexidine is poorly absorbed from the gastrointestinal Bactigras; Cepton; Chlorohex; Corsodyl; Curasept; CX Powder; acid, although the hypochlorite ion may also contribute. tract and skin. Eczmol; Elgydium; Hibiscrub; Hibitane; Hydrex; Periogardt; The activity of most of the compounds decreases with Savlon Antiseptic Wound Wash; Serotulle; Spotoway; Steripod increase of pH, the activity of solutions of pH 4 to 7 being Neonates. Occasional reports of the percutaneous absorp Chlorhexidine Gluconate; Unisept; Uriflex C; Ukr. : Hexicon greater than those of higher pH values. However, stability is tion of chlorhexidine in neonates and infants include a (reKCHKOH); USA: Betasept; Biopatch; Dyna-Hex; Exidine; Hibi usually greater at an alkaline pH. study in which chlorhexidine was detected in low concen clenst; Hibistat; Peridex; Periochip; Periogard; Surgilube; The potency of chlorine disinfectants is expressed in Venez. : trations in the venous blood of 5 of 24 infants after wash Peridont. terms of available chlorine. This is based on the concept of ing them with a preparation containing chlorhexidine Multi-ingredient Preparations. Numerous preparations are listed chlorine gas (Cb) as the reference substance. Two atoms of gluconate 4% (Hibiscrub); no adverse effects were noted. 1 in Volume B. chlorine (2 X Cl) yield in water only one molecule of Low concentrations have been found2 in the venous blood hypochlorous acid (on which activity is based), while of neonates after the topical use of a powder containing Pharmacopoeial Preparations hypochlorites and chloramines yield one molecule of chlorhexidine l %. Percutaneous absorption of chlorhexi BP 2014: Chlorhexidine Gluconate Eye Drops; Chlorhexidine hypochlorous acid for each atom of chlorine as shown in the dine was reported in preterm neonates (but not full-term Gluconate Gel; Chlorhexidine Irrigation Solution; Chlorhexidine following equations: Mouthwash; Lidocaine and Chlorhexidine Gel; infants) treated with chlorhexidine 1% in alcohol for neo USP 36: Chlorhexidine Gluconate Oral Rinse; Chlorhexidine Cl +H 0 +-+ HOCI +H++cl natal cord care; no such absorption occurred when a dust 2 2 Gluconate Topical Solution. NaOCl + H 0 +-+ HOC! + NaOH ing powder containing chlorhexidine 1% and zinc oxide 2 3% was used. 3 Thus the assayed chlorine in such compounds has to be
l. Cowen J, et al. of chlorhexidine from the intact skin of multiplied by 2 to produce 'available chlorine'. The term newborn infants. 1979; 54: 379-83. Chlorinated Lime 'active chlorine' has been used confusingly for either 2. Alder VG, et al. Comparison of hexachlorophane and chlorbexidine pesmanche; Bleaching c!ora{}a: Caic0ria 'available chlorine' (Cl ) or 'combined chlorine' (Cl). powders in prevention of neonatal infection. Arch Dis Child 1980; 55: Pov1d10r: Cal 2 277-80. Chlorata: Because they have relatively low residual toxicity, Calcii Hypocr.lorls; C?lCi\Jtn• Hypochlorite; .Calciun; . 3. Aggett PJ, et al. Percutaneous absorption of chlorhexidine in neonatal Hypocruorosum; Calx Cb.isodium hypochlorite, septic; Clean Derm; Endure Cida; Endure Scrub; First Aid being exhausted by combination with organic material. It is tosylchloran1ide sodium, chlorinated lime, chlorine dioxide, Antiseptic Skin Cleanser; Germi Stat; Hibidilt; Hibitane; Oro used to disinfect faeces, urine, and other organic material, or halazone are used. After satisfying the chlorine demand Clense; Oronine Ht; Perichlor; Peridex; Periogard; Prevora l; and as a cleansing agent for lavatories, drains, and effluents. (the amount of chlorine needed to react with organic matter Provon Antiseptic; Soft Care CHG Antimicrobial; Solu-IV CHG; Chlorinated lime is used in the preparation of Surgical and other substances), a free-residual content of 0.2 to Solunet C; Solunet Mousse; Soluprep; Spectra Gramt; Stan Chlorinated Soda Solution (BPC 1973) (Dakin's Solution) 0.4ppm 'available chlorine' should be maintained, though hexidine; Sterixin; Tegaderm CHG; Vap; Chile: AB; Bucoseptil; which has been employed as a wound disinfectant, and more is required for alkaline waters with a pH of 9 or more. Dentilim; Elugel; Freshmel; Garonseptt; Graneodin; Oralgene; For the disinfection of potentially contaminated water a China: Chlorinated Lime and Boric Acid Solution (BP 1993 ), Ortoxine; Perio-Aid; Periokint; Jiu Tai (1L#i); Kou Tai concentration of I ppm is recommended. Excessive residual ( Ya Nuo Cz. : Corsodyl; Septofort; Denm.: (Eusol), which has been used as a disinfectant lotion and D#); (:fli'i;fi); chlorine may be removed by adding a little citric acid or Hibitane; Periochip; Fin.: Corsodyl; Klorhexol; Meridol Perio wet dressing, sometimes with equal parts of liquid paraffin. sodium thiosulfate. CHX; Periochip; Travahex; Fr.: Baseal; Biorgasept; Cetavlex; However, such solutions are irritant when applied Collunovar; Corsodyl; Dermachromet; Diaseptyl; Dosiseptine; undiluted, and are no longer recommended for use in this For use in small swimming pools, sodium or calcium Elgydium; Elugel; Euraxsepti; Exoseptoplix; Hibidil; Hibiscrub; way. In addition, there is some evidence that such chlorine hypochlorite may be added daily to maintain a free-residual I Hibisprintt; Hibitane; Paroex; Plurexidt; Prexidine; Septeal; releasing solutions may delay wound healing (see 'available chlorine' concentration of to 3 ppm. Tosyl Septidose; Septivon; Septivoncare; Ger.: Bactigras; Cathejell St; Disinfection, Wounds under Uses and Administration of chloramide sodium, chlorinated lime, and the isocyanurates Chlorhexamed; Cidegol C; Dynexan Proaktiv; Endosgel; Lemo Sodium Hypochlorite, p. I 7 69.1). (see Troclosene, p. 1774. 1) may also be used. To minimise cin CXt; Meridol med CHX; Gr.: Hibitane; Lifo-Scrub; Perio� irritation of the eyes, maintain disinfectant activity, prevent Homoeopathy chip; Periogard; Plak Out; Spitaderm; Hong Kong: Bacidint; precipitation of salts, and prevent metal corrosion, a pH of Chlorinated lime has been used in homoeopathic Corsodyl; Hexidinet; Hexisolt; Hydrex; Qualikin; Scanlin; 7.2 to 7.8 should be maintained. medicines under the following nan1es: Calcarea hypochlor Vick-Hexidinet; Hung.: Septofort; India: A'Fresh; Afresho; Solutions of chlorine-releasing compounds are also used ata; Calc hypochlor. Arofil; C-Nate; Clohex; CMW; Coglu; Dencure; Dentrosym; in wound desloughing and disinfection (but see Disinfec� Evergaurd; Freshex; Glihex; Hexabir; Hexatrin; Hexide; Hexi tion: Wounds, under Sodium Hypochlorite, p. 1769.1). dine; Hexigel; Hexiprep; Hygeen; Indent; Inhex; M-Rinse; A s s Tr nt ti s Maghex-M; Microshield; Mouden; Nitra�Hex; Nusept; 02- clv�r. e...� �! ! .. e.CJ.t.'!'.e. . �.CJ.��.. P.r. �".� ?.� .. Fresh; Orahex; Orbiz; Orinse; Orofact; Osihex; Indon.: Medi· As for Sodium�e. Hypochlorite, p. 1769.2. Adverse Effects and Treatment scrubt; Irl. : Cepton Medicated; Corsodyl; Hibiscrub; Hibitane; Chlorine gas is irritant and corrosive producing inflamma Hydrex; Periochip; Prevora Stage l; Savlon Antiseptic Wound i tion, burns, and necrosis. Inhalation may result in Wash; Sterets Unisept; Israel: Bactoscrubt; Bactoseptt; Clear Preparat ons coughing, choking, headache, dyspnoea, dizziness, expect dent; Corsodyl; GynaHex; Hexatatet; KxG; Medident; Feria Pharmacopoeial Preparations oration of frothy white sputum (which may be blood chip; Pharma�Dentixt; Septadine Scrub; Septal; Septalone; Sep BPC 1973: Surgical Chlorinated Soda Solution. tal; Tarodent; Xylodentt; Ital.: Benodent CLX; Broxodin; stained), a burning chest pain, and nausea. Bronchospasm, Clarifex; Clomirext; Clorexifarm; Clorosan; Corsodyl; Dempol; laryngeal oedema, acute pulmonary oedema with cyanosis, Dentosan Parodontale; Eburos; Ekuba; Esoform Mani�Cute; and hypoxia may occur. There may be vomiting and Esosan Gel Mani; Golasan; Iodosan Clorexidina; Lenil; Master Chlorine development of acidosis. Death may result from hypoxia. Aid; Neo-Destomygen; Neomercurocromo; Neoxene; Neoxinal; Some of the toxicity of chlorine may be due to its 925;. Chlor; Parodontax; Periochip; Periogard Chlorohex; Plak Out; Plak; dissolution in tissue water to produce hydrochloric acid and Ci2=7MO Sicura3; Triseptilt; Malaysia: Baby Shield Plus; Baaigras; hypochlorite. After exposure to chlorine, conjunctivitis may
AJl cross-references refer to entries in Volume A