Oral Miconazole Research Articles

Drug-drug interactions and masking effects in sport doping: influence of miconazole administration on the urinary concentrations of endogenous anabolic steroids

We have investigated the influence of oral miconazole administration on the urinary concentrations of endogenous anabolic androgenic steroids of doping relevance, specifically considering all these compounds routinely monitored in doping control analysis, in the framework of the steroidal module of the “athlete biological passport”, and other steroids, including dehydroepiandrosterone, 5α-dihydrotestosterone, and the hydroxylated metabolites recently proposed as additional markers of the intake of testosterone-related steroids (16α-hydroxy-androsterone, 16α-hydroxy-etiocholanolone, 6β-hydroxy-androsterone, 6β-hydroxy-etiocholanolone, 7α-hydroxy-dehydroepiandrosterone, and 7β-hydroxy-dehydroepiandrosterone). Urinary concentrations of the final metabolic products of the glucocorticoid biosynthetic pathways (11β-hydroxy-androsterone and 11β-hydroxy-etiocholanolone, the formerly used as an endogenous reference compound for the gas chromatography–combustion-isotope ratio mass spectrometry confirmation analysis) were also monitored. Two healthy Caucasian volunteers exhibiting physiologically high testosterone/epitestosterone ratios and elevated concentrations of the main target steroids were selected for the study. Miconazole was administered orally (500 mg/day) for 1 week. Multiple urine samples were collected for 1 week before and during the treatment, and analyzed according to a validated analytical procedure based on gas chromatography–electron ionization-mass spectrometry in selected ion monitoring mode. Our results indicated that oral administration of miconazole decreased the urinary concentrations of androsterone, and to a lesser extent, of etiocholanolone (both detected as the sum of free and glucuronated steroids), and consequently the androsterone/testosterone and androsterone/etiocholanolone ratios. Furthermore, the urinary concentrations of 16α-hydroxy-etiocholanolone, 16α-hydroxy-androsterone, 7β-hydroxy-dehydroepiandrosterone, 6β-hydroxy-etiocholanolone, 7α-hydroxy-dehydroepiandrosterone, 6β-hydroxy-androsterone, 11β-hydroxy-androsterone, and 11β-hydroxy-etiocholanolone were significantly suppressed. This evidence suggests the potential intake of miconazole whenever the urinary steroid profile is characterized by abnormally low concentrations of the above-mentioned steroids.

Methylene Blue-Mediated Photodynamic Inactivation Followed by Low-Laser Therapy versus Miconazole Gel in the Treatment of Denture Stomatitis.

Photodynamic therapy (PDT) appears to be an effective method for the in vitro and in vivo inactivation of Candida spp., but no clinical trials in this context have yet been conducted. The aim of this study was to compare the effect of oral miconazole gel to PDT combined with low-power laser (LPL) therapy in the treatment of denture stomatitis. Forty participants with clinical and microbiological diagnoses of type II denture stomatitis were randomly allocated to two treatment groups (PDT and miconazole gel), each with 20 individuals. The PDT group was submitted to one session of methylene blue-mediated PDT plus two sessions of low-laser therapy twice a week for 15 days. The miconazole group was submitted to the drug four times a day for 15 days. Forty percent of the patients achieved clinical and microbiological resolution of denture stomatitis after methylene blue-mediated photodynamic inactivation followed by low-laser therapy. The cure rate associated with miconazole was 80% (p < 0.05). Fifteen days after the end of treatment, the recurrence rate was 25% in patients treated with PDT combined with LPL therapy and 12.5% in patients treated with miconazole. Miconazole gel provides better results than a protocol combining methylene blue-mediated PDT and LPL therapy in the treatment of type II denture stomatitis.

Interaction of miconazole oral gel with warfarin and cyclosporine in a patient with nephrotic syndrome.

It is well known that miconazole inhibits cytochrome P450 (CYP). However, this drug in oral gel form is believed not to absorb into systemic circulation, and therefore not to inhibit CYP. We experienced a case of increased oral bioavailability of warfarin and cyclosporine with this gel for treatment of oral candidiasis in a patient with nephrotic syndrome. Her prothrombin time-international normalized ratio (PT-INR) increased from 2 to 7.25, and the cyclosporine concentration at 2h after final dosing (C2) increased from 633.8 to 1396.5ng/ml 6days after the coadministration. These problems were resolved by termination of the gel and switching to amphotericinB gargle. We further detected a significant amount of miconazole in her plasma, directly showing for the first time in a patient with this interaction that oral miconazole gel was actually absorbed into systemic circulation. Because warfarin and cyclosporine are often used simultaneously by nephrologists, caution should be applied with combined use of these drugs and oral miconazole gel to avoid adverse reaction.

Management of oropharyngeal candidiasis with localized oral miconazole therapy: efficacy, safety, and patient acceptability

Oropharyngeal candidiasis is a very common localized infection of the mucus membranes of the oropharynx that is most commonly caused by the patient’s own commensal Candida albicans. It is the most common opportunistic infection affecting patients with the human immunodeficiency virus (HIV) and is also quite common in patients with hematological malignancies. Effective treatment options are of high importance given the worldwide incidence of these disease states and the potential for development of oropharyngeal candidiasis in these patients. Various systemic and topical treatment options for patients with oropharyngeal candidiasis have existed for many years. Miconazole buccal tablets have recently been approved by the US Food and Drug Administration for the treatment of oropharyngeal candidiasis. Clinical trials have demonstrated noninferiority in the treatment of oropharyngeal candidiasis when compared with clotrimazole troches in patients with HIV and against miconazole gel in patients with head and neck cancer. Miconazole buccal tablets exhibit few drug interactions because of low systemic absorption and are generally well tolerated with a safety profile similar to comparators. The once-daily dosing schedule may improve patient adherence compared with topical alternatives; however, the cost of therapy may be a barrier for some patients and should be considered by prescribers compared with alternative treatments.

Warfarin and miconazole oral gel interactions: analysis and therapy recommendations based on clinical data and a pharmacokinetic model

Miconazole is a strong inhibitor of CYP2C9, one of the main enzymes involved in the metabolism of warfarin. Concurrent use of the two drugs leads to potentially serious adverse effects. Although it is often assumed that use of the oral miconazole gel is acceptable with concomitant warfarin, because of the low bioavailability following buccal administration, drug-drug interactions have been reported following such use. We aimed to investigate case reports of such interactions and develop a pharmacokinetic model to model such interactions. The Medline database from 1966 to October 2010 was used for literature search. Case reports of the potentiation of the anticoagulant effects of warfarin, such as the elevation of prothrombin time (INR), by concomitant administration of warfarin and miconazole oral gel were collected. We quantitatively estimated the extent of inhibition of warfarin metabolism by orally administered miconazole gel and compared our findings with case reports. Metabolism of (S)-warfarin is inhibited potently following administration of a standard dose (200-400 mg/day in Japan) of miconazole gel. This may lead to in an increase in the blood concentration of warfarin and lead to serious adverse effects. The literature reports of clinical interactions with concomitant use of those drugs show that other factors may amplify the effects of any increase in blood concentration. We summarize all reported, clinically significant, cases of drug interaction between miconazole oral gel and warfarin. Pharmacokinetic modelling shows that concomitant administration of warfarin and miconazole oral gel can lead to substantial increase in warfarin concentration. However, our PK/PD model fails to capture the dramatic increases seen in INR values, and hence bleeding complications, reported in the literature. Taken together, the evidence suggests that concomitant use of miconazole gel and warfarin should be avoided. Even over-the-counter products containing miconazole should be used with caution by patients receiving warfarin.

Intractable Oral Candidosis As An Indicator Of HIV Infection In Infants

Objective: Human immunodeficiency virus infection is assuming an epidemic proportion in the developing world, and infants are increasingly being infected and seen with clinical features and serological evidence of HIV infection in IIorin. Intractable oral candidosis is one of the clinical features of the disease seen commonly infants. This study examined the possible association between intractable oral thrush and HIV infections in infancy Design: This is a prospective study carried out over a 3 year period. Subjects & Method: Infants presenting with oral candidosis who did not respond to two courses of oral mycostatin drop given thrice daily over 2 weeks period were studied. Such infects were screened for HIV infection after parental consent. Another group of infants who did not have oral candidosis but were screened for HIV infection due to other indication served as controls for the purpose of comparison. Results: Thirty two infants with intractable oral candidosis were screened and 28 (87.5%) were HIV positive whilst 2 out of 20 (10%) cases without intractable oral candidosis screened other reasons were positive for HIV infection (X 2 = 21.48, p=0.000036, odds ratio = 24.54 “RR” = 5.42). The presence of intractable oral cadidosis in HIV infected infants has a sensitivity of 93.3% and specificity of 81.8%, with a positive predictive vale of 85.3%. The oral lesions cleared completely with oral miconazole gel given thrice daily for two weeks Conclusion: The finding of extensive intractable oral candidosis which is refractory to simple oral antifungal agent therapy in infants should raise the suspicion of HIV infection and such infants should be screened for HIV after parental consent KEY WORDS: Intractable oral thrush, infants, HIV infection, miconazole gel Nigerian Journal of Clinical Practice Vol.6(1) 2003: 42-45

Overanticoagulation associated with combined use of antifungal agents and coumarin anticoagulants.

Several case reports have associated combined use of coumarins and antifungal agents with overanticoagulation. However, we are not aware of epidemiologic studies that quantify the risk of overanticoagulation caused by antifungal agents. We conducted a follow-up study in a large population-based cohort to investigate the antifungal agents that are associated with overanticoagulation during therapy with coumarins. All patients in the Rotterdam Study who were treated with acenocoumarol or phenprocoumon in the study period from April 1, 1991, through Dec 31, 1998, and for whom international normalized ratio data were available were followed up until an INR > or =6.0, the end of their treatment, death, or the end of the study period. Proportional hazards regression analysis was used to estimate the risk of an INR > or =6.0 in relation to concomitant use of an oral anticoagulant and antifungal agents, after adjustment for several potentially confounding factors such as age, gender, hepatic dysfunction, malignancies, and heart failure. Of the 1124 patients in the cohort, 351 had an INR > or =6.0. The incidence rate was 6.9 per 10,000 treatment days. Oral miconazole most strongly increased the risk of overanticoagulation with an adjusted relative risk of 36.6 (95% confidence interval [CI], 12.4-108.0). In this study among outpatients of an anticoagulant clinic who were on a regimen of coumarins, oral miconazole was especially strongly associated with overanticoagulation. Awareness of these drug interactions and more frequent monitoring of INR values during the initial stages of treatment with some antifungal drugs in patients taking coumarins may minimize the risk of bleeding complications. The concurrent use of miconazole and coumarins should be discouraged.

Oral miconazole for the treatment of Candida-Associated denture stomatitis

Oral miconazole for the treatment of Candida-Associated denture stomatitis

Warfarin-Miconazole Interaction

To the Editor. —The editorial by Hochman et al, published in the August 1982Archives(142:1440-1442), was an excellent review of the relationship of antibiotics to the adverse effect of bleeding caused by the drugs and drug interactions with warfarin sodium. The antifungal agent, miconazole, should be added to the list of anti-infective agents known to potentiate the effect of warfarin sodium. Watson et al1described two patients who were therapeutically and safely anticoagulated on warfarin for several months following the insertion of prosthetic mitral valves. A marked increase in prothrombin time with blood blisters and hematomas on the limbs occurred 11 to 12 days after administering miconazole, 250-mg tablets four times daily, for suspected fungal infections. The prothrombin time returned to the premiconazole level after therapy with the antifungal drug was discontinued. Oral miconazole is unavailable in the United States. However, according to the drug package insert for

A Case of Primary Cutaneous Cryptococcosis Successfully Treated With Miconazole

An 81-year-old man with primary cutaneous cryptococcosis of the left forearm was treated with intravenous and oral miconazole nitrate. Culture for Cryptococcus became negative within three weeks. The ulcer healed within 25 days after treatment was started. Follow-up examination 1 1/2 years later showed no evidence of recurrent infection.

Miconazole in Oral Candidiasis

Twenty-four patients were treated with oral miconazole (250 mg) for a total of 35 episodes of oral candidiasis. Sixteen had various forms of leukaemia and all were massively predisposed to fungal infection because of granulocytopenia and treatment with prednisolone and antibiotics. Clinical cure was observed in all 35 of the treated episodes, with a mean treatment time of five days, cure being observed in two to three days. When patients violating the protocol were excluded, the mycological cure rate was 97%. In 21 episodes there was a recurrence less than one month after miconazole treatment, probably because of reinfection. No side-effects ascribable to miconazole were observed, even in the severely debilitated patients, and the orally administered drug appeared to be superior to other commercially available antimycotic preparations.

Systemic antifungal potential, safety, biotransport and transformation of micronazole nitrate

Miconazole nitrate was investigated in 169 normal volunteers for its safety and its antifungal action on the bronchial and intestinal flora after oral administration, and for its biotransport and transformation after oral, intravaginal and percutaneous administration. — Oral doses of 3 g a day for nine weeks produced no haematological, biochemical or ECG abnormalities. Within the first week of treatment, miconazole significantly reduced the number of fungal colonies in cultures of sputum and faeces, and inhibited tetracycline-induced fungal overgrowth in the faeces. Oral miconazole significantly improved dermatophytosis. — Miconazole was absorbed moderately well from the gastrointestinal tract and was virtually not absorbed from the mucous membrane and skin.