Introduction
Miconazole is a broad-spectrum azole antifungal with some activity against Gram-positive bacteria as well. It is widely used to treat mucosal yeast infections, including both oral and vaginal infections; although intravenous miconazole is no longer available, a wide variety of suppositories, creams, gels, and tablet-based products are available. Miconazole is thought to act primarily through the inhibition of fungal CYP450 14α-lanosterol demethylase activity.
It is currently available as a variety of prescription and over the counter products. Despite having been in clinical use for an extended period, resistance to miconazole among susceptible organisms is relatively low.
Uses
Miconazole is an azole antifungal with broad-spectrum activity used to treat fungal infections affecting the vagina, mouth and skin, including candidiasis.
Miconazole is indicated for the local treatment of oropharyngeal candidiasis in adult patients and for the adjunctive treatment of diaper dermatitis complicated by candidiasis in immunocompetent patients aged four weeks and older. Miconazole is available as both a suppository and cream for the treatment of vaginal yeast infections and the relief of associated vulvar itching and irritation. Lastly, miconazole cream is effective in treating athlete's foot (tinea pedis), jock itch (tinea cruris), ringworm infections (tinea corporis), pityriasis (formerly tinea) versicolor, and cutaneous candidiasis.
Associated Conditions
Pharmacodynamics
Miconazole is an azole antifungal that functions primarily through inhibition of a specific demethylase within the CYP450 complex. As miconazole is typically applied topically and is minimally absorbed into the systemic circulation following application, the majority of patient reactions are limited to hypersensitivity and cases of anaphylaxis. Patients using intravaginal miconazole products are advised not to rely on contraceptives to prevent pregnancy and sexually transmitted infections, as well as not to use tampons concurrently.
Mechanism of Action
Miconazole is an azole antifungal used to treat a variety of conditions, including those caused by Candida overgrowth. Unique among the azoles, miconazole is thought to act through three main mechanisms. The primary mechanism of action is through inhibition of the CYP450 14α-lanosterol demethylase enzyme, which results in altered ergosterol production and impaired cell membrane composition and permeability, which in turn leads to cation, phosphate, and low molecular weight protein leakage.
In addition, miconazole inhibits fungal peroxidase and catalase while not affecting NADH oxidase activity, leading to increased production of reactive oxygen species (ROS). Increased intracellular ROS leads to downstream pleiotropic effects and eventual apoptosis.
Lastly, likely as a result of lanosterol demethylation inhibition, miconazole causes a rise in intracellular levels of farnesol. This molecule participates in quorum sensing in Candida, preventing the transition from yeast to mycelial forms and thereby the formation of biofilms, which are more resistant to antibiotics. In addition, farnesol is an inhibitor of drug efflux ABC transporters, namely Candida CaCdr1p and CaCdr2p, which may additionally contribute to increased effectiveness of azole drugs.
Absorption
Miconazole given to healthy volunteers as a single 50 mg oral tablet produced a mean Cmax of 15.1 ± 16.2 mcg/mL, a mean AUC0-24 of 55.2 ± 35.1 mcg*h/mL, and a median Tmax of 7 hours (range 2.0-24.1). In these patients measurable plasma concentrations ranged from 0.5 to 0.83 mcg/mL.
Topical miconazole is absorbed poorly into the systemic circulation. In pediatric patients aged 1-21 months given multiple topical applications of miconazole ointment for seven days, the plasma miconazole concentration was less than 0.5 ng/mL in 88% of the patients, with the remaining patients having a concentration of 0.57 and 0.58 ng/mL, respectively. Similarly, patients. administered with a vaginal 1200 mg ovule had a mean Cmax of 10.71 ng/mL, mean Tmax of 18.4 hours, and mean AUC0-96 of 477.3 ng*h/mL.
Volume of Distribution
A 1200 mg miconazole vaginal suppository resulted in a calculated apparent volume of distribution of 95 546 L while a 100 mg vaginal cream yielded an apparent volume of distribution of 10 911L.
Protein Binding
In vitro data suggests that miconazole binds human serum albumin, however, the clinical significance of this observation is unclear.
Route of Elimination
Miconazole is excreted through both urine and feces; less than 1% of unchanged miconazole is recovered in urine.
Half Life
Miconazole has a terminal half-life of 24 hours.
Toxicity
Miconazole overdose has not been reported. Patients experiencing an overdose are at an increased risk of severe adverse effects such as headache, skin irritation, diarrhea, nausea, vomiting, abdominal pain, and dysgeusia. Symptomatic and supportive measures are recommended.
Miconazole has an oral LD50 of 500 mg/kg in rats.
Food Interactions
No interactions found.
Dosage
Oropharyngeal candidosis-
- Infants 4-24 months: 1.25 ml (1⁄4 measuring spoon) of gel, applied 4 times day after meals.
- Adult and children 2 years of age and older: 2.5 ml (1⁄2 measuring spoon) of gel, applied 4 times a day after meals.
- Infants (4 months of age or above): Children and adults who have difficulty swallowing tablets: 20 mg per kg body weight per day, in four divided doses. The daily dose should not exceed 250 mg (10 ml gel) four times daily.
dose and continue your usual course.
Miconazole Cream: Sufficient Miconazole Cream should be applied to cover affected areas twice daily (morning and evening) in patients with tinea pedis, tinea cruris, tinea corporis and cutaneous candidiasis and once daily in patients with tinea versicolor. If Miconazole Cream is used in intertriginous areas it should be applied sparingly and smoothed in well to avoid maceration effects.
Early relief of symptoms (2 to 3 days) is experienced by the majority of patients and clinical improvement may be seen fairly soon after treatment is begun.All lesions usually disappear after 2 to 5 weeks.Prolong treatment for 10 days to prevent relapse. However, Candida infections, tinea cruris and corporis should be treated for two weeks and tinea pedis for one month in order to reduce the possibility of recurrence.
