      Document 0175
 DOCN  DRG0175
 UNIQUE IDENTIFIER        DRG-0072
 NAME OF SUBSTANCE        Clotrimazole [USAN 1996]
 REGISTRY NUMBER          23593-75-1
 RELATED REGISTRY NUMBER  37594-65-3
 RELATED REGISTRY NUMBER  37594-66-4
 RELATED REGISTRY NUMBER  37594-67-5
 RELATED REGISTRY NUMBER  37655-24-6
 STANDARD CHEMICAL NAME   1H-Imidazole,
                          1-((2-chlorophenyl)diphenylmethyl)- [USAN
                          1996]
 SYNONYMS                 Canesten [Merck Index 1989]
 SYNONYMS                 Empecid [Merck Index 1989]
 SYNONYMS                 Gyne-Lotrimin [Merck Index 1989]
 SYNONYMS                 Lotrimin Cream [PDR 1995]
 SYNONYMS                 Mycelex [USAN 1996]
 SYNONYMS                 Mycelex G Vaginal Tablets [PDR 1995]
 SYNONYMS                 Mycelex-7 Vaginal Tablets [PDR 1995]
 SYNONYMS                 Mycelex Troches [PDR 1995]
 SYNONYMS                 Mycelex Solution [USP DI 1995]
 SYNONYMS                 Lotrimin AF Solution [USP DI 1995]
 SYNONYMS                 Lotrimin Lotion [PDR 1995]
 SYNONYMS                 Lotrimin Topical Solution [PDR 1995]
 SYNONYMS                 Myclo [Merck Index 1983]
 SYNONYMS                 Mycosporin [Merck Index 1989]
 SYNONYMS                 Trimysten [Merck Index 1989]
 SYNONYMS                 (Chlorotrityl)imidazole [Merck Index 1983]
 SYNONYMS                 (2-Chlorophenyl)-diphenyl-1-imidazolylmethane
                          [Merck Index 1983]
 SYNONYMS                 Diphenyl(2-chlorophenyl)(1-imidazolyl)methane
                          [Merck Index 1989]
 SYNONYMS                 Diphenyl(2-chlorophenyl)-1-imidazolylmethane
                          [Merck Index 1983]
 SYNONYMS                 Imidazole,
                          1-(o-chloro-alpha,alpha-diphenylbenzyl)-(8CI)
                          [Merck Index 1983]
 SYNONYMS                 1-((2-Chlorophenyl)diphenylmethyl)-1H-imidazo-
                          le (9CI) [Merck Index 1983]
 SYNONYMS                 1-(alpha-(2-Chlorophenyl)benzhydryl)-imidazol-
                          e [Merck Index 1989]
 SYNONYMS                 1-(o-Chloro-alpha,alpha-diphenylbenzyl)imidaz-
                          ole [Merck Index 1989]
 SYNONYMS                 1-(o-Chlorophenyldiphenylmethyl)imidazole
                          [Merck Index 1983]
 SYNONYMS                 1-(o-Chlorotrityl)imidazole [Merck Index
                          1989]
 SYNONYMS                 Canifug [Merck Index 1989]
 SYNONYMS                 Mono-Baycuten [Merck Index 1989]
 SYNONYMS                 Mycofug [Merck Index 1989]
 SYNONYMS                 Pedisafe [Merck Index 1989]
 SYNONYMS                 Rimazole [Merck Index 1989]
 SYNONYMS                 Tibatin [Merck Index 1989]
 PROTOCOL ID NUMBERS      FDA 012M
 PROTOCOL ID NUMBERS      NIAID ACTG 981
 SECONDARY SOURCE ID      Bay-B 5097 [Merck Index 1989]
 SECONDARY SOURCE ID      FB 5097 [Merck Index 1989]
 SECONDARY SOURCE ID      HSDB 3266 [CHEMLINE]
 SECONDARY SOURCE ID      Bay 5097 [USAN 1996]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Clotrimazole is fungistatic,
                          may be fungicidal (depending on its
                          concentration), and has some antibacterial
                          activity. It inhibits biosynthesis of
                          ergosterol and other sterols, damaging the
                          fungal cell wall membrane, altering its
                          permeability, potentially causing loss of
                          essential intracellular elements. It also
                          inhibits the biosynthesis of triglycerides
                          and phospholipids by fungi. It inhibits
                          oxidative and peroxidative enzyme activity,
                          causing intracellular buildup of toxic levels
                          of hydrogen peroxide, which may contribute to
                          deterioration of subcellular organelles and
                          cellular necrosis. It is poorly and
                          erratically absorbed, even when swallowed.
                          Absorbed clotrimazole is metabolized in the
                          liver to inactive compounds; it induces
                          hepatic microsomal activity which accelerates
                          its own catabolism. Duration of action is up
                          to 3 hours. Elimination of clotrimazole is
                          principally through the fecal route. [USP DI
                          1995]
 DISEASES STUDIED/TREATED Treatment and prophylaxis of oropharyngeal
                          candidiasis and treatment of vulvovaginal
                          candidiasis [USP DI 1995]
 CLASSIFICATION CODE      Antifungal [PDR 1995]
 OTHER MAJOR USES         Oral therapy for oropharyngeal candidiasis
                          (thrush) caused by Candida species; topical
                          therapy for tinea infections and for
                          cutaneous candidiasis caused by C. albicans
                          [USP DI 1995]
 ADVERSE EFFECTS          Oral administration: may cause abdominal or
                          stomach cramping or pain, diarrhea, nausea,
                          or vomiting. Topically: erythema, stinging,
                          blistering, peeling, edema, pruritus,
                          urticaria, burning, and general irritation of
                          the skin. [PDR 1995] [USP DI 1995]
 CONTRAINDICATIONS        Contraindicated in patients with
                          hypersensitivity to clotrimazole. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Synthetic chlorinated
                          imidazole derivative closely related to
                          miconazole [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C22H17C1N2 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C76.63%, H4.97%,
                          Cl0.28%, N8.12% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 344.85 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 147-149 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Slightly soluble in water,
                          benzene, toluene, soluble in acetone,
                          chloroform, ethyl acetate, and DMF [Merck
                          Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Odorless, white to
                          yellow crystalline powder [AHFS Drug
                          Information 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Lozenges (10 mg), vaginal cream
                          (50 mg), tablets (100 mg, 500 mg), topical
                          solution (1%). [USP DI 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral (lozenges), vaginal
                          insertion (cream or tablets), solution
                          (topical). [USP DI 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store below 30 C in tight
                          containers, protect from freezing. [USP DI
                          1995]
 MANUFACTURERS            Schering-Plough
 MANUFACTURERS            Miles Incorporated Pharmaceutical Division
 REFERENCES               Powderly WG, Finkelstein D, Feinberg J, Frame
                          P, He W, van der Horst C, Koletar SL, Eyster
                          ME, Carey J, Waskin H, et al. A randomized
                          trial comparing fluconazole with clotrimazole
                          troches for the prevention of fungal
                          infection in patients with advanced human
                          immunodefieciency virus infection. N Engl J
                          Med. 1995 Mar 16;332(11):700-5.
 REFERENCES               Sangeorzan JA, Bradley SF, He X, Zarins LT,
                          Ridenour GL, Tiballi RN, Kauffman CA.
                          Epidemiology of oral candidiasis in
                          HIV-infected patienst: colonization,
                          infection, treatment, and emergence of
                          fluconzale resistance. Am J Med. 1994
                          Oct;97(4):339-46.
 REFERENCES               Gooskens V, Ponnighaus JM, Clayton Y,
                          Mkandawire P, Sterne JA. Treatment of
                          superficial mycoses in the tropics:
                          Whitfield's ointment versus clotrimazole. Int
                          J Dermatol. 1994 Oct;33(10):738-42.
 REFERENCES               Greenspan D. Treatment of oropharyngeal
                          candidiasis in HIV-positive patients. J Am
                          Acad Dermatol. 1994 Sep;31(3 Pt 2):S51-5.
 REFERENCES               Pons V, Greenspan D, Debruin M. Therapy for
                          oropharyngeal candidiasis in HIV-infected
                          patients: a randomized, prospective
                          multicenter study of oral fluconazole versus
                          clotrimazole troches. J Acquir Immune Defic
                          Syndr. 1993 Dec;6(12):1311-6.
 REFERENCES               Higgins S, Woolley PD, Chandiok S. Comparison
                          of topical clotrimazole, oral fluconazole and
                          oral itraconazole in acute vulvovaginal
                          candidiasis. Int Conf AIDS. 1993 Jun
                          6-11;9(1):274 (abstract no. PO-A36-0840).
 REFERENCES               Lalor E, Rabeneck L. Esophageal candidiasis
                          in AIDS. Successful therapy with clotrimazole
                          vaginal tablets taken by mouth. Dig Dis Sci.
                          1991 Mar;36(3):279-81.
 REFERENCES               Lucatorto FM, Franker C, Hardy WD, Chafey S.
                          Treatment of refractory oral candidiasis with
                          fluconazole. A case report. Oral Surg Oral
                          Med Oral Pathol. 1991 Jan;71(1):42-4.
 REFERENCES               Koletar SL, Russell JA, Fass RJ, Plouffe JF.
                          Comparison of oral fluconazole and
                          clotrimazole troches as treatment for oral
                          candidiasis in patients infected with human
                          immunodeficiency virus. Antimicrob Agents
                          Chemother. 1990 Nov;34(11):2267-8.
 REFERENCES               Lichter S, Palenicek J, Yamaguchi E, Barbacci
                          M, Chaisson RE. Fluconazole or clotrimazole
                          troche for oropharyngeal candidiasis in HIV-1
                          positive patients. Int Conf AIDS. 1990 Jun
                          20-23;6(1):218 (abstract no. Th.B.385).
 ENTRY MONTH              8910
 LAST REVISION DATE       951201
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
