This article provides a review of the use of flavoxate hydrochloride in the treatment of urge incontinence. It outlines the pharmacology, mode of action, toxicology and pharmacokinetic studies which have been carried out, and then reviews the clinical studies, including those involving patients with benign prostatic hypertrophy. The effects of dosages of 600–1200 mg/day are compared, particularly regarding safety and tolerability factors. Finally, alternative therapies to flavoxate hydrochloride (α-adrenergic receptor blockers, oxybutinin chloride, terodiline hydrochloride, emepronium bromide and imipramine) are summarized. The article is written in the knowledge of recent evidence which indicates that flavoxate hydrochloride exhibits only weak anticholinergic activity on receptors involved in the control of the lower urinary tract.
GrazianiGCazzulaniPPanzarasaR: Flavoxate: general properties and activity in the urinary tract. In: Flavoxate (CornelliUGrazianiG, eds). Geneva: Bioscience Ediprint, 1983; pp 7–19.
2.
RuffmannRSartaniA: Flavoxate, a drug with smooth muscle relaxing activity. Int J Drugs Exp Clin Res1987; 13: 57–62.
3.
CapraAPaggiG: Impiego del flavoxato nel trattamento della minaccia d'aborto e della minaccia di parto prematuro. Minerva Ginecol1972; 24: 400–404.
4.
PolitoPMDe PalmaV: Il flavossato nel parto pilotate, Minerva Ginecol1977; 29: 331–334.
5.
ServadioC: The use of flavoxate in cystitis and renal colic. Curr Med Res Opin1974; 2: 449–454.
6.
FallMFrankenbergSFrisenM: 45600 svenskar kan ha urininkontinens Endast var fjarde soker hjalp for besvaren. Lakartidningen1985; 82: 2054–2056.
7.
FarleyD: Incontinence comes out of the closet. FDA Consumer1987 (March); 5–9
8.
FossbergEBeislandHOSanderS: Urinary incontinence in old age. Ann Chir Gynaecol1982; 71: 228–231.
9.
ResnickNMYallaSV: Management of urinary incontinence in the elderly. N Engl J Med1985; 313: 800–805.
10.
AbbiatiGACesaraniRNardiD: Receptor binding studies of REC 15/2053, and other bladder spasmolytics. Pharm Res1988; 5: 430–433.
11.
MayuzumiKWatanabeKTamaraK: Effects of oxybutinin hydrochloride on the urinary bladder and urethra in in-situ preparations. Nippon Yakurigaku Zasshi1986; 87: 557–571.
12.
MorikawaKVamauchiTKatoH: Effects of 3-methyl-4-oxo-2-phenyl-N-(2-piperidinyl) ethyl-4H-1-benzopyran-8-carboxyamide hydrochloride monohydrate (FL-155), a new antipollakiuria agent, on rhythmic bladder contractions in anesthetized rats. Nippon Yakurigaku Zasshi1986; 88: 355–361.
13.
BradingAFMostwinJLSibleyGNA: The role of smooth muscle and its possible involvement in diseases of the lower urinary tract. Clin Sci1986; 70 (suppl 14): 7s–13s.
14.
ResnickNMYallaSV: Detrusor hyperactivity with impaired contractile function. J Am Med Assoc1987; 257: 3076–3081.
15.
MoiseyCUStephensonTPBrendlerCB: The urodynamic and subjective results of treatment of detrusor instability with oxybutinin chlorideBr J Urol1980; 53: 472–475.
16.
GaudenzRWeilA: Motor urge incontinence: diagnosis and treatment. Urol Int1980; 35: 1–12.
17.
BrooksMEBrafZF: Oxybutinin chloride (Ditropan)–clinical uses and limitations. Paraplegia1980; 18: 64–68.
18.
PietraCCazzulaniP: Effects of flavoxate on urinary bladder contraction, micturition reflex and urodynamic parameters. Il Farm1986; 41: 267–273.
19.
CazzulaniPPietraCAbbiatiGA: Pharmacological activities of the main metabolite of flavoxate, 3-methylflavone-8-carboxylic acid. Arzneimittelforsch1988; 38: 379–382.
20.
CazzulaniPPanzarasaRLucaC: Pharmacological studies on the mode of action of flavoxate. Arch Int Pharmacodyn Ther1984; 268: 301–312.
21.
RasmussenH: The calcium messenger system. N Engl J Med1986; 314: 1094–1101.
22.
RasmussenH: The calcium messenger system. N Engl J Med1986; 314: 1164–1170.
23.
MalkowiczSBWeinAJRuggieriMR: Comparison of calcium antagonist properties of antispasmodic agents. J Urol1987; 138: 667–670.
24.
BensonGSSarshikSARaezerDM: Bladder muscle contractility. Comparative effects and mechanisms of action of atropine, propantheline, flavoxate, and Imipramine. Urology1977; 9: 31–35.
25.
BredaG: L'elettromanometria pielo-ureterale nello studio del meccanismo d'azione del flavossato. Proceedings of a Round Table Meeting held in Abbazia, Italy, 30–31 March 1974. Milan: Recordati, 1975; pp 43–51.
26.
MorselliVPavlicaP: Studio radiologico degli effetti del flavossato sull'attività motoria della pelvi e dell'uretere. Proceedings of a Round Table Meeting held in Abbazia, Italy, 30–31 March 1974. Milan: Recordati, pp 23–36.
27.
OnnisAGrellaPMarchesoniD (eds): I Farmaci in Gravidanza 2nd edn. Padova: Piccin Editore, 1983; pp 216–217.
28.
VeroneseMBarzaghiD: Experimental studies in vitro and in vivo on the mutagenicity of flavoxate. Arzneimittelforsch1987; 37: 528–531.
29.
TajanaACovaA: Current status of knowledge of flavoxate pharmacokinetics. Flavoxate Workshop, Cernobbio (Como), 28–29 September 1981. In: Flavoxate (CornelliUGrazianiG, eds). Geneva: Bioscience Ediprint, 1983; pp 33–52.
30.
JonasUPetriEKisselJ: Effect of flavoxate on hyperactive detrusor muscle. Eur Urol1979; 5: 106–109.
31.
BrielRCGassnerK: First experience with flavoxate in bladder-conditioned types of incontinence in gynaecology. Geburtshilfe Frauenheilkd1980; 40: 242–245.
32.
BriggsRSCasteldenCMAsherMJ: The effect of flavoxate on uninhibited detrusor contractions and urinary incontinence in the elderly. J Urol1980; 123: 665–666.
33.
BaertL: Controlled double-blind trial of flavoxate in painful conditions of the lower urinary tract. Curr Med Res Opin1975; 2: 631–635.
34.
DelaereKPJMichielsHGEDebruyneFMJ: Flavoxate hydrochloride in the treatment of detrusor instability. Urol Int1977; 32: 377–381.
35.
MeyhoffHHGerstenbergTCNordlingJ: Placebo–the drug of choice in female motor urge incontinence?Br J Urol1983; 55: 34–37.
36.
AagaardJReutherKStimpelH: A comparison between the combination emepronium bromide/flavoxate and emepronium bromide in the treatment of detrusor instability. Urol Int1983; 38: 191–192.
37.
RobinsonJMBrocklehurstJC: Emepronium bromide and flavoxate hydrochloride in the treatment of urinary incontinence associated with detrusor instability in elderly women. Br J Urol1983; 55: 371–376.
38.
JarvisGJ: A controlled trial of bladder drill and drug therapy in the management of detrusor instability. Br J Urol1981; 53: 565–566.
39.
CardozoLDStantonSL: An objective comparison of the effects of parenterally administered drugs in patients suffering from detrusor instability. J Urol1979; 122: 58–59.
40.
CaineM: The present role of alpha-adrenergic blockers in the treatment of benign prostatic hypertrophy. J Urol1986; 136: 1–4.
41.
SpeakmanMJSethiaKKFellowsCJ: A study of the pathogenesis, urodynamic assessment and outcome of detrusor instability associated with bladder outflow obstruction. Br J Urol1987; 59: 40–44.
42.
RokujoM: A clinical study of Bladderon tablets in patients with benign prostatic hypertrophy. Shinyaku To Rinsho1981; 30: 1478–1480.
43.
IkegamiS: A clinical study of combined therapy with Eviprostat and Bladderon tablets in BPH patients. Shinyaku To Rinsho1981; 30: 1478–1480.
44.
YoshidaH: Clinical effects of Bladderon tablets against nocturnal pollakiuria in BPH patients. Shinyaku To Rinsho1981; 30: 1617–1619.
45.
NiijimaMUenoAKawabeK: A multicenter clinical trial of flavoxate hydrochloride. Nishinippon Hinyokika1981; 43: 1055–1063.
46.
FujinagaT: A clinical study of Bladderon in BPH patients. Sinryo To Shinyaku1982; 19: 1974–1975.
47.
MilaniRScalambrinoSCarreraS: Flavoxate hydrochloride for urinary urgency after pelvic radiotherapy: comparison of 600 mg versus 1200 mg daily dosages. J Int Med Res1988; 16: 71–74.
48.
MilaniRScalambrinoSCarreraS: Comparison of flavoxate hydrochloride in daily dosages of 600 versus 1200 mg for the treatment of urgency and urge incontinence. J Int Med Res1988; 16: 244–248.
49.
GururajVJ: Flavoxate hydrochloride in the treatment of childhood enuresis. Clin Med1975; 82: 25–27.
50.
AndoT: Clinical experience with flavoxate hydrochloride in enuretic children. Nish J Urol1983; 45: 185–191.
51.
KoyanagiT: Clinical evaluation of flavoxate on voiding disorders. Nish J Urol1975; 37: 281–287.
52.
NakataE: Clinical and experimental evaluation of flavoxate hydrochloride in the field of neurology. Nish J Urol1975; 37: 141–149.
53.
TokunagoT: Clinical evaluation of AK-123 (flavoxate hydrochloride) in urological area: effect on disturbances in urination. Nish J Urol1975; 37: 634–642.
54.
ShapiroELeporH: A new receptor in human and canine prostate: the alpha2 adrenergic receptor. J Urol part 2 1985; 133: 133A, abstract 79.
55.
CaineMMazouzBRossiniBM: The effect of nicergoline on the lower urinary tract muscle. Urol Res1984; 12: 287.
56.
RonchiFMargonatoACeccardiR: Symptomatic treatment of benign prostatic obstruction with nicergoline: a placebo controlled clinical study and urodynamic evaluation. Urol Res1982; 10: 131.
57.
SineK: Oxybutynin chloride. On Continuing Practice1984; 11: 31–33.
58.
LishPMLabuddeJAPetersEL: Oxybutynin—a musculotropic antispasmodic drug with moderate anticholinergic action. Arch Int Pharmacodyn1965; 156: 467–488.
59.
NilvebrandLSparfB: Dicyclomine, benzhexol and oxybutynin distinguish between subclasses of muscarinic binding sites. Eur J Pharmacol1986; 123: 133–143.
60.
GajewskiJBAwadSA: Oxybutinin versus propantheline in patients with multiple sclerosis and detrusor hyperreflexia. J Urol1986; 135: 966–968.
BeislandHOFossbergE: The effects of terodiline and meladiazine on severe motor urge incontinence in geriatric patients. J Am Geriatr Soc1985; 33: 29–32.
63.
BowmanJvon GarreltsB: Emepronium bromide–the effect on bladder pressure and urinary flow in healthy subjects. Scan J Urol Nephrol1973; 7: 153–157.
64.
HebjornSWalterS: Treatment of female incontinence with emepronium bromide. Detruso hyperreflexia in multiple sclerosis and urge incontinence in postmenopausal women treated with emepronium bromide (Cetiprin). Urol Int1978; 33: 120–129.
65.
UlmstenUAnderssonKE: The effects of emeprone on intravesical and intraurethral pressure in women with urgency incontinence. Scan J Urol1977; 11: 103–109.
66.
ObrinkABunneG: Treatment of urgency by installation of emepronium bromide in the urinary bladder. Scand J Urol Nephrol1978; 12: 215–218.
67.
RitchAEGeorgeCFCastledenCM: A second look at emepronium bromide in urinary incontinence. Lancet1977; i: 504–506.
68.
CastledenCMGeorgeCFRenwickAG: Imipramine–a possible alternative to current therapy for urinary incontinence in the elderly. J Urol1981; 125: 318–320.
69.
PatrickDLEricksonP: Assessing health related quality of life for clinical decision making. In: Quality of Life: Assessment and Application (WalkerSRRosserRM, eds). Boston: MTP Press, 1988; pp 9–49.
