Miconazole

416.13

416.13

245-324-5

170986

DTXSID6023319

D01AC02|A - Alimentary tract and metabolism|D - Dermatologicals|G - Genito urinary system and sex hormones|J - Antiinfectives for systemic use|S - Sensory organs

2933290090

27

5.3

Solid

1.4±0.1 g/cm3

184-185 °C

555.1°C at 760 mmHg

87°(189°F)

1.625

Freely soluble in alcohols or acetone. Also soluble in DMF or chloroform. Insoluble in water

Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances.

6.07E-13mmHg at 25°C

III

6.1(b)

3249

3

22

22-36

NI4770000

Xn

Stable at room temperature in closed containers under normal storage and handling conditions.

P301 + P312 + P330

H302-H413

|Warning|H302 (99.61%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P273, P301+P312, P330, P391, and P501|Aggregated GHS information provided by 258 companies from 10 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

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.[MSDS]

_In vitro_ data suggests that miconazole binds human serum albumin, however, the clinical significance of this observation is unclear.

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.|FDA Label|Treatment of burns

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.

Compounds that specifically inhibit STEROL 14-DEMETHYLASE. A variety of azole-derived ANTIFUNGAL AGENTS act through this mechanism. (See all compounds classified as 14-alpha Demethylase Inhibitors.)|Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP2C9. (See all compounds classified as Cytochrome P-450 CYP2C9 Inhibitors.)|Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP3A. (See all compounds classified as Cytochrome P-450 CYP3A Inhibitors.)|Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues. (See all compounds classified as Antifungal Agents.)

Miconazole given to healthy volunteers as a single 50 mg oral tablet produced a mean C_max of 15.1 ± 16.2 mcg/mL, a mean AUC_0-24 of 55.2 ± 35.1 mcg\*h/mL, and a median T_max 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 C_max of 10.71 ng/mL, mean T_max of 18.4 hours, and mean AUC_0-96 of 477.3 ng\*h/mL.|Miconazole is excreted through both urine and feces; less than 1% of unchanged miconazole is recovered in urine.|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.

Miconazole is metabolized in the liver and does not give rise to any active metabolites.

Miconazole has a terminal half-life of 24 hours.

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.

Brentan

Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients