Clotrimazole dosing

Miconazole. Miconazole nitrate [22832-87-7] (Fig. 2), the 1-phenethyl-imidazole derivative first described in 1969, interferes at low doses with the cytochrome P-450 dependent ergosterol biosynthesis in yeasts and fungi. The result is accumulation of C-14 methylated sterols on the one hand and reduction of the ergosterol levels in the membranes on the other hand (12). Analogous to clotrimazole, this leads to a disturbance in the membranes it results in inhibition of ceU repHcation, mycelium development (in C. albicans) and finally, ceU death. High concentrations of miconazole, which may be achieved with topical use, disturb the orientation of phosphoHpids in the membranes, which produces leaks (13). 

Prophylaxis Nystatin, clotrimazole, Inhibit P-450 3A4 monitor CSA and TAC levels decrease doses... 

Fluconazole is very effective in the treatment of infections with most Candida spp. Thrush in the end-stage AIDS patient, often refractory to nystatin, clotrimazole, and ketoconazole, can usually be suppressed with oral fluconazole. AIDS patients with esophageal candidiasis also usually respond to fluconazole. A single 150-mg dose has been shown to be effective treatment for vaginal candidiasis. A 3-day course of oral fluconazole is effective treatment for Candida urinary tract infection and is more convenient than amphotericin B bladder irrigation. Preliminary findings suggest that Candida endophthalmitis can be successfully treated with fluconazole. Stable nonneutropenic patients with candidemia can be adequately treated with fluconazole, but unstable, immunosuppressed patients should initially receive... 

Lawrence, A. Houang, E. Hiscock, E. Wells, M. Colh, E. Scatigna, M. Single dose therapy of vaginal candidiasis a comparative trial of fenticonazole vaginal ovules versus clotrimazole vaginal tablets. Curr. Med. Res. Opinion 1990,12, 114-120. 

Topical vaginal administration of even relatively high doses of clotrimazole did not result in systemic toxicity (9). 

A 40-year-old Afro-American woman developed an exfoliative rash and blistering and swelling of the tongue (12). A diagnosis of Stevens-Johnson syndrome was made. She had not taken any medications other than two doses of a formulation that contained G. biloba. Her condition responded to treatment with prednisolone, clotrimazole, and famotidine. G. biloba was withdrawn and no further events occurred. However, 5 months later she still had tenderness in the soles of the feet, peeling of the nails, and discoloration of the skin. 

Topical therapy with clotrimazole or nystatin for 7 days is usually adequate for treating mucocutaneous candidiasis in most solid-organ transplant patients. Use of topical therapy will reduce the number of systemic drugs that these patients receive and hence minimize the risk of drug-drug interactions. Failure to respond to topical agents warrants the use of fluconazole. Low-dose amphotericin B 5-10 mg daily for 7 to 10 days is reserved for the unusual cases of treatment failure. 

Sobel JD, Brooker JD, Stein GE, et al. Single oral dose of fluconazole compared wifli conventional clotrimazole topical flier y of Candida vaginitis. Am J Obstet Gynecol 1995 172 1263-1268. 

Absorption of clotrimazole is less than 0.5% after application to the intact skin from the vagina, it is 3 to 10%. Fnngicidal concentrations remain in the vagina for as long as 3 days after application of the drug. The small amount absorbed is metabolized in the liver and excreted in bile. In adults, an oral dose of 200 mg per day will give rise initially to plasma concentrations of 0.2 to 0.35 pg/mL, followed by a progressive decline. 

Clotrimazole has been reported to cure dermatophyte infections in 60 to 100% of cases. The cure rates in cutaneous candidiasis are 80 to 100%. In vulvovaginal candidiasis, the cure rate is usually above 80% when the 7-day regimen is used. A 3-day regimen of 200 mg once a day appears to be similarly effective, as does single-dose treatment (500 mg). Recurrences are common after all regimens. The cure rate with oral troches for oral and pharyngeal candidiasis may be as high as 100% in the immunocompetent host. 

Clotrimazole and nystatin may he used topically (not orally) for vaginal candidiasis. The activity of griseofulvin is limited to dermatophytes. Huconazole in a single ortd dose is usually effective in vaginal candidiasis. The answer is (C). 

Early studies with intravaginal clotrimazole revealed that only a small fraction (3 to 10% of the dose) was absorbed systemically, and that this was rapidly metabolised. ... 

When tacrolimus is given orally, its serum levels are considerably increased by oral fluconazole, and tacrolimus dose reductions may be needed. Itraconazole, ketoconazole, posaconazole, voriconazole, and oral clotrimazole, also raise tacrolimus levels. There is some evidence that the levels of intravenous tacrolimus are minimally affected by fluconazole and ketoconazole. In theory it is possible that miconazole oral gel may also interact with tacrolimus. 

The interactions of tacrolimus with itraconazole and ketoconazole also appear to be established, and the manufacturer states that nearly all patients will require tacrolimus dose reductions when given these drugs. Information about clotrimazole is limited, but on the basis of the case report and study it would be prudent to monitor tacrolimus levels, and adjust the dose as necessary. 

Clotrimazole (Bay b5097) will soon be on clinical trial in the U.S.A. Clinical studies in Germany demonstrated the compound to be active by the oral route in single cases of candidal pneumonia and bronchitis, and aspergilloma, but not in a case of chromomycosis. High doses produced liver hyp rteophy in rats. As an inducer of liver oxidative enzymes, clotrimazole is as active as phenobarbital. ... 

Morton CO, Chau M, Stack C (2014) In vitro combination therapy using low dose clotrimazole and photodynamie therapy leads to enhanced killing of the dermatophyte Trichophytrai rubrum. BMC Microbiol 14 261/1—261/9... 

Clotrimazole (Bay b 509 ) has been the object of additional clinical and laboratory evaluation. In children with albicans pyelonephritis who were dosed at a level of 70-200 mg/kg/day for 10 to 4o days, good response was noted in all patients although relapses frequently occurred after the... 

A cream containing 1% w/w clotrimazole for cutaneous and mucocutaneous application. Adult dose application to the infected area two or three times a day, continuing for 14 days after all visible signs of infection have healed. 

Less than 1% of clotrimazole enters the systemic circulation following topical application whilst between 3% and 10% of a dose has been reported to do so following vaginal adminisUation. As a result, very little of an applied dose (typically <1%) enters into the systemic circulation. Additionally, with higher systemic doses achieved via vaginal application, the course duration 1-6 days, allied to low blood concentrations, is not enough to induce metabolism. 

Like clotrimazole, miconazole was originally developed as an intravenous and oral antifungal agent. The intravenous formulation was discontinued due to anaphylactic reactions associated with the injection vehicle excipient, poly-oxyl 35 Castor Oil (Cremophor EL), used to enhance the solubility of miconazole. Unlike clotrimazole, repeated administration does not induce the hepatic microsomal enzymes involved in its own metabolism. Following oral administration, around 20% of a dose is systemically absorbed where it undergoes oxidadve O-dealkylation and oxidative N-dealkylation prior to excredon (Fig. 24.5). Approximately 40% of the administered dose is excreted unchanged in the faeces. The faecal route of excredon for... 

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