Clotrimazole is used orally in the form of a lozenge for the topical treatment of oropharyngeal candidiasis which has been confirmed by potassium hydroxide microscopic mounts and/or culture. Clotrimazole lozenges also are used prophylactically to reduce the incidence of oropharyngeal candidiasis in patients who are immunocompromised as the result of immunosuppressive therapy (e.g., corticosteroids, antineoplastic agents, radiation therapy) used for the treatment of leukemia, solid tumor, or renal transplantation. Clotrimazole lozenges should not be used for the treatment of systemic fungal infections, including systemic candidiasis.
Treatment of Oropharyngeal Candidiasis
In one study in cancer patients with oropharyngeal candidiasis receiving one 10-mg clotrimazole lozenge 5 times daily, the median duration of oral candidiasis following initiation of clotrimazole therapy was 4 days. In another study, oral topical administration of clotrimazole in the form of a 10-mg lozenge administered 5 times daily was effective in the treatment of oropharyngeal candidiasis in some patients who did not respond to topical oral nystatin or topical gentian violet therapy. However, when clotrimazole therapy was stopped, the infection invariably recurred within 2-4 weeks, presumably because the underlying defect that predisposed the patients to oropharyngeal candidiasis was not corrected.
Topical therapy with oral clotrimazole is used in the treatment of oropharyngeal candidiasis in patients with human immunodeficiency virus (HIV) infection. Some clinicians consider topical therapy with oral clotrimazole or oral nystatin the treatment of choice for uncomplicated oropharyngeal candidiasis in HIV-infected patients and recommend that systemic antifungal agents (e.g., oral fluconazole, oral itraconazole, oral ketoconazole) be reserved for the treatment of oropharyngeal candidiasis unresponsive to topical agents or for the treatment of severe oropharyngeal candidiasis with esophageal involvement. However, other clinicians prefer to use an oral azole antifungal agent for initial therapy of oropharyngeal candidiasis in HIV-infected individuals. Topical oral therapy with clotrimazole is ineffective for the treatment of esophageal candidiasis in HIV-infected patients.
Prophylaxis of Oropharyngeal Candidiasis
Oral clotrimazole in the form of a lozenge has been effective for prophylaxis against oropharyngeal candidiasis in neutropenic patients receiving immunosuppressive therapy (e.g., corticosteroids, antineoplastic agents, radiation therapy) for treatment of leukemia, solid tumor, or renal transplantation. However, safety and efficacy of oral clotrimazole for prophylaxis of oropharyngeal candidiasis in patients immunocompromised as the result of primary immunodeficiency or other causes have not been determined. Although oral clotrimazole has been used for prophylaxis against oropharyngeal candidiasis in HIV-infected individuals, the drug is no longer included in the prophylaxis guidelines of the Prevention of Opportunistic Infections Working Group of the US Public Health Service and Infectious Diseases Society of America (USPHS/IDSA). If prophylaxis of oropharyngeal candidiasis is indicated in HIV-infected individuals, the USPHS/IDSA recommends oral fluconazole or, alternatively, oral itraconazole solution.
Dermatophytoses and Cutaneous Candidiasis
Clotrimazole is used topically as a cream, lotion, or solution for the treatment of tinea corporis, tinea cruris, and tinea pedis caused by T. rubrum, T. mentagrophytes, E. floccosum, or M. canis and for the treatment of cutaneous candidiasis. Clotrimazole topical cream or solution also may be used topically for self-medication of tinea pedis, tinea cruris, and tinea corporis caused by T. rubrum, T. mentagrophytes, E. floccosum, or M. canis. The combination preparation containing clotrimazole and betamethasone dipropionate has been used topically for the treatment of tinea pedis, tinea cruris, and tinea corporis caused by T. rubrum, T. mentagrophytes, or E. floccosum.
Tinea corporis and tinea cruris generally can be effectively treated using a topical antifungal; however, an oral antifungal may be necessary if the disease is extensive, dermatophyte folliculitis is present, the infection is chronic or does not respond to topical therapy, or the patient is immunocompromised because of coexisting disease or concomitant therapy. Many clinicians consider topical imidazole-derivative azole antifungals (e.g., clotrimazole, econazole, ketoconazole, miconazole, oxiconazole, sulconazole) or topical allylamine antifungals (e.g., naftifine, terbinafine) the drugs of first choice for the topical treatment of tinea corporis or tinea cruris, although other topical antifungal agents (e.g., ciclopirox olamine, butenafine hydrochloride, tolnafate, undecylenic acid) also can be effective in the treatment of these infections. While topical antifungals usually are effective for the treatment of uncomplicated tinea manuum and tinea pedis, an oral antifungal usually is necessary for the treatment of hyperkeratotic areas on the palms and soles, for chronic moccasin-type (dry-type) tinea pedis, and for the treatment of tinea unguium (onychomycosis).
Clinical studies to date indicate that clotrimazole is effective for the topical treatment of these infections and appears to be equivalent in efficacy and safety to other topical imidazole derivatives (e.g., econazole, ketoconazole). Additional controlled, comparative studies are needed to establish the relative efficacy of clotrimazole and other currently available topical antifungal agents. Like other imidazole derivatives (e.g., econazole, ketoconazole, miconazole, oxiconazole, sulconazole) and ciclopirox olamine, clotrimazole has an advantage over some other topical antifungal agents (e.g., nystatin, tolnaftate) in the treatment of mixed infections or for empiric treatment pending identification of the causative organism, since the drug is active against both dermatophytes and Candida.
Pityriasis (Tinea) Versicolor
Clotrimazole is used topically as a cream, lotion, or solution for the treatment of pityriasis (tinea) versicolor caused by Malassezia furfur (Pityrosporum orbiculare or P. ovale). Pityriasis (tinea) versicolor generally can be treated topically with an imidazole-derivative azole antifungal (e.g., clotrimazole, econazole, ketoconazole, miconazole, oxiconazole, sulconazole), an allylamine antifungal (e.g., terbinafine), ciclopirox olamine, or certain other topical therapies (e.g., selenium sulfide 2.5%). However, an oral antifungal (e.g., itraconazole, ketoconazole) may be indicated, with or without a topical agent, in patients who have extensive or severe infections or who fail to respond to or have frequent relapses with topical therapy.
Clotrimazole is used intravaginally for the treatment of vulvovaginal candidiasis. Prior to initial use of clotrimazole in a woman who has signs and symptoms of uncomplicated vulvovaginal candidiasis, the diagnosis should be confirmed either by demonstrating yeast or pseudohyphae with direct microscopic examination of vaginal discharge (saline or 10% potassium hydroxide [KOH] wet mounts or Gram stain) or by culture; identifying Candida by culture in the absence of symptoms is not an indication for antifungal treatment since approximately 10-20% of women harbor Candida or other yeasts in the vagina. Clotrimazole vaginal tablets or cream may be used for self-medication of vulvovaginal candidiasis in otherwise healthy, nonpregnant women who have been previously diagnosed by a clinician and are having a recurrence of similar symptoms. When an adequate response is not achieved following a course of clotrimazole therapy for vulvovaginal candidiasis or there is recurrence of symptoms within 2 months, appropriate microbiologic studies should be performed to confirm the diagnosis and identify unusual Candida species (e.g., C. glabrata).
Up to 75% of women reportedly have at least one episode of vulvovaginal candidiasis and 40-45% have 2 or more episodes during their lifetime, but a small percentage of women (up to 5%) have recurrent vulvovaginal candidiasis (i.e., 4 or more episodes of symptomatic vulvovaginal candidiasis each year). While certain factors may precipitate a sporadic attack of vulvovaginal candidiasis and have been associated with an increased risk for recurrent vulvovaginal candidiasis (e.g., uncontrolled diabetes mellitus, pregnancy, oral contraceptive use, corticosteroid or other immunosuppressive therapy, immunodeficiency, use of intravaginal sponges or devices, repeated courses of topical or systemic antibacterial agents), these factors are not present in most women who have recurrent episodes.
Azole antifungals (imidazole and triazole derivatives) are considered the drugs of choice for the treatment of vulvovaginal candidiasis. The US Centers for Disease Control and Prevention (CDC) and other clinicians generally recommend that uncomplicated vulvovaginal (defined as vulvovaginal candidiasis that is mild to moderate, sporadic or infrequent, most likely caused by Candida albicans, or occurring in immunocompetent women) should be treated with an intravaginal azole antifungal (e.g., butoconazole, clotrimazole, miconazole, terconazole, tioconazole) given in appropriate single-dose or short-course regimens or, alternatively, oral fluconazole given in a single-dose regimen. These regimens generally have been associated with clinical and mycologic cure rates of 80-90% in otherwise healthy, nonpregnant women with uncomplicated infections, and there is no clear evidence that any one intravaginal azole antifungal regimen is superior to any other intravaginal azole regimen available for the treatment of these infections. While intravaginal nystatin also can be used for the treatment of uncomplicated vulvovaginal candidiasis, it generally is less effective than intravaginal azole antifungals. A longer duration of therapy (i.e., 7-14 days) with an intravaginal or oral azole antifungal generally is necessary for the treatment of complicated vulvovaginal candidiasis, including recurrent and severe disease. Complicated vulvovaginal candidiasis is defined as infections that are recurrent or severe, caused by Candida other than C. albicans, or occurring in pregnant women or women with underlying disease such as uncontrolled diabetes, debilitation, or immunosuppression.
(See Complicated and Recurrent Vulvovaginal Candidiasis under Uses: Vulvovaginal Candidiasis.)
Clinical trials using clotrimazole vaginal tablets in the treatment of vulvovaginal candidiasis have shown that, in nonpregnant women, a treatment regimen using two 100-mg tablets daily for 3 days is as effective as a regimen using one 100-mg tablet daily for 7 days; however, in pregnant women, symptomatic vulvovaginal candidiasis may be more difficult to cure and the 3-day regimen may be less effective than the 7-day regimen. In clinical trials using clotrimazole vaginal cream, 7-14 days of treatment were generally effective; however, treatment regimens of 14 days had a higher cure rate than shorter regimens.
Vulvovaginal candidiasis usually is not acquired through sexual activity, and treatment of sexual partner(s) is not recommended but may be considered in women who have recurrent infections. However, male sexual partners who have symptomatic balanitis or penile dermatitis may benefit from treatment with a topical antifungal agent to relieve symptoms.
Complicated and Recurrent Vulvovaginal Candidiasis
Optimum regimens for the treatment of recurrent vulvovaginal candidiasis (usually defined as 4 or more episodes of symptomatic vulvovaginal candidiasis each year) have not been established. Although each individual episode caused by C. albicans may respond to usual short-course intravaginal antifungal regimens or a single-dose of oral fluconazole, a longer duration of initial therapy may be necessary to achieve mycologic remission and chronic maintenance therapy may be necessary to prevent relapse. The CDC recommends use of an initial intensive regimen consisting of 7-14 days of an intravaginal azole antifungal or a 3-dose regimen of oral fluconazole (100-, 150-, or 200-mg doses given every third day for a total of 3 doses) followed by a maintenance antifungal regimen (given for 6 months). For the maintenance regimen, the CDC recommends oral fluconazole (100-, 150-, or 200-mg doses once weekly). If this oral regimen cannot be used, some clinicians recommend intravaginal clotrimazole (200 mg twice weekly or 500 mg once weekly) or other intravaginal treatments used intermittently. These maintenance regimens can be effective in reducing recurrent infections; however, 30-50% of women will have recurrent disease once maintenance therapy is discontinued.
The response rate to short-course antifungal regimens is lower in patients with severe vulvovaginal candidiasis (i.e., extensive vulvar erythema, edema, excoriation, and fissure formation) and either a 2-dose regimen of oral fluconazole (150 mg repeated 3 days later) or 7-14 days therapy with an intravaginal azole antifungal is recommended for these infections. These more prolonged regimens may also be necessary for the treatment of vulvovaginal candidiasis in women with underlying debilitating medical conditions (e.g., those with uncontrolled diabetes mellitus or those receiving corticosteroid therapy).
For the treatment of vulvovaginal candidiasis during pregnancy, the CDC recommends use of a 7-day regimen of an intravaginal azole antifungal.
Vulvovaginal candidiasis may occur more frequently and may be more severe in women with human immunodeficiency virus (HIV) infection than in women without HIV infection and these infections have been recognized as an early manifestation of acquired immunodeficiency syndrome (AIDS) in women. While optimum therapy for recurrent vulvovaginal candidiasis in HIV-infected women has not been established, there is no evidence to date that these women have a lower response rate to the intravaginal or oral antifungal regimens usually recommended for the treatment of vulvovaginal candidiasis. Therefore, the CDC and other clinicians recommend that treatment of vulvovaginal candidiasis in HIV-infected women be the same as that in women without HIV infection.
Recurrent vulvovaginal candidiasis rarely may be caused by resistant strains of C. albicans or, more commonly, by other Candida with reduced susceptibility to azole antifungals (e.g., C. glabrata). It has been suggested that repeated treatment of recurrent vulvovaginal candidiasis with intravaginal azole antifungals and widespread and/or injudicious use of these agents for self-medication of vulvovaginal candidiasis may favor the selection of Candida resistant to azole antifungals. Optimum therapy for the treatment of vulvovaginal candidiasis caused by Candida with reduced susceptibility to azole antifungals has not been determined to date. For the treatment of vulvovaginal candidiasis caused by Candida other than C. albicans, the CDC recommends 7-14 days of therapy with an antifungal agent other than fluconazole; if recurrence occurs, intravaginal boric acid (600-mg capsule once daily for 2 weeks) is recommended. Referral to a specialist is advised.