Miconazol

170

159 - 163 °C

This chemical does not meet GHS hazard criteria for 1% (1 of 104) of reports.

Warning

H302 (98.1%): Harmful if swallowed [Warning Acute toxicity, oral]；H400 (54.8%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]；H410 (54.8%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]；H413 (39.4%): May cause long lasting harmful effects to aquatic life [Hazardous to the aquatic environment, long-term hazard]

P264, P270, P273, P301+P317, P330, P391, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 104 reports by companies from 11 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Reported as not meeting GHS hazard criteria per 1 of 104 reports by companies.；There are 10 notifications provided by 103 of 104 reports by companies with hazard statement code(s).；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

IMAP assessments - 1H-Imidazole, 1-[2-(2,4-dichlorophenyl)-2-[(2,4-dichlorophenyl)methoxy]ethyl]-: Environment tier I assessment；IMAP assessments - 1H-Imidazole, 1-[2-(2,4-dichlorophenyl)-2-[(2,4-dichlorophenyl)methoxy]ethyl]-: Human health tier I assessment

Miconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Miconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms, inhibit purine uptake, and impair triglyceride and/or phospholipid biosynthesis.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

miconazole

DILI Negative

Topical

DOI:10.1016/j.drudis.2019.09.022

◉ Summary of Use during Lactation；Because miconazole has poor absorption from the skin and vagina and has poor oral bioavailability, it is unlikely to adversely affect the breastfed infant, including after topical application to the nipples. However, miconazole ointment appears to have no advantage over lanolin for treating sore nipples during breastfeeding and a survey of members of the Academy of Breastfeeding Medicine found topical miconazole is rarely prescribed to nursing mothers to treat thrush. Any excess cream or ointment should be removed from the nipples before nursing. Only water-miscible cream or gel products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins via licking.；◉ Effects in Breastfed Infants；Relevant published information was not found as of the revision date.；◉ Effects on Lactation and Breastmilk；In a randomized, double-bind trial, lanolin was compared to an all-purpose nipple ointment containing mupirocin 1%, betamethasone 0.05%, and miconazole 2% for painful nipples while nursing in the first 2 weeks postpartum. The two treatments were equally effective in reducing nipple pain, nipple healing time, breastfeeding duration, breastfeeding exclusivity rate, mastitis and nipple symptoms, side effects or maternal satisfaction with treatment.

◈ What is miconazole?；Miconazole is a medication that has been used to treat fungal infections. As a cream, it has been used topically (on the skin) to treat skin infections and as a cream or suppository (inserted into the vagina) to treat vaginal infections. Some brand names for miconazole are Desenex®, Lomitrin AF®, Monistat®, Micatin® and Mitrazole®.Sometimes when women find out they are pregnant, they think about changing how they take their medication, or stopping their medication altogether. However, it is important to talk with your healthcare providers before making any changes to how you take your medication. Your healthcare providers can talk with you about the benefits of treating your condition and the risks of untreated illness during pregnancy.；◈ What should I do if I think I have a vaginal yeast infection while pregnant?；Women are more likely to get yeast infections during pregnancy than at other times. If you think you have a vaginal yeast infection, it is important to see your healthcare provider to be sure the infection is yeast before trying to treat it on your own. If you have another type of infection, you may need different treatment.；◈ I use miconazole. Can it make it harder for me to get pregnant?；Using miconazole is not expected to make it harder to get pregnant.；◈ Does using miconazole increase the chance of miscarriage?；Miscarriage is common and can occur in any pregnancy for many different reasons. One study found a small increased chance for miscarriage with the use of miconazole, but there were several problems with this study that could have affected the results. Other studies have not found that miconazole increases the chance of miscarriage.；◈ Does taking miconazole increase the chance of birth defects?；Birth defects can happen in any pregnancy for different reasons. Out of all babies born each year, about 3 out of 100 (3%) will have a birth defect. We look at research studies to try to understand if an exposure, like miconazole, might increase the chance of birth defects in a pregnancy.Topical or vaginal medications enter the body in lower amounts than oral (pill) medications. This means less medication reaches the developing fetus. Since topical and vaginal miconazole are not well absorbed, they are unlikely to increase risks to a pregnancy. Most studies have shown that miconazole at low doses (；◈ Does using miconazole increase the chance of other pregnancy-related problems?；Studies have not been done to see if miconazole increases the chance for pregnancy-related problems such as preterm delivery (birth before week 37) or low birth weight (weighing less than 5 pounds, 8 ounces [2500 grams] at birth).；◈ Does using miconazole in pregnancy affect future behavior or learning for the child?；Studies have not been done to see if miconazole can cause behavior or learning issues for the child.；◈ Breastfeeding while using miconazole:；There are no studies looking at the use of miconazole use during breastfeeding. However, because only small amounts of the medication are expected to pass into breastmilk when miconazole is used topically or vaginally, it is not expected to cause side effects in a nursing child. Miconazole cream has been used directly on infants under the care of a healthcare provider to treat fungal infections. If used on the nipples, any excess cream or ointment should be removed from the nipples before nursing. Be sure to talk to your healthcare provider about all your breastfeeding questions.；◈ If a man uses miconazole, could it affect his fertility or increase the chance of birth defects?；Studies have not been done to see if miconazole could affect male fertility (ability to get a woman pregnant) or increase the chance of birth defects above the background risk. In general, exposures that fathers or sperm donors have are unlikely to increase risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.

D01AC02

D - Dermatologicals；D01 - Antifungals for dermatological use；D01A - Antifungals for topical use；D01AC - Imidazole and triazole derivatives；D01AC02 - Miconazole

S - Sensory organs；S02 - Otologicals；S02A - Antiinfectives；S02AA - Antiinfectives；S02AA13 - Miconazole

G - Genito urinary system and sex hormones；G01 - Gynecological antiinfectives and antiseptics；G01A - Antiinfectives and antiseptics, excl. combinations with corticosteroids；G01AF - Imidazole derivatives；G01AF04 - Miconazole

J - Antiinfectives for systemic use；J02 - Antimycotics for systemic use；J02A - Antimycotics for systemic use；J02AB - Imidazole derivatives；J02AB01 - Miconazole

A - Alimentary tract and metabolism；A07 - Antidiarrheals, intestinal antiinflammatory/antiinfective agents；A07A - Intestinal antiinfectives；A07AC - Imidazole derivatives；A07AC01 - Miconazole

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.

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.

7NNO0D7S5M

MICONAZOLE

Established Pharmacologic Class [EPC] - Azole Antifungal

Chemical Structure [CS] - Azoles

Miconazole is an Azole Antifungal.

MICONAZOLE

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.

Compounds that specifically inhibit STEROL 14-DEMETHYLASE. A variety of azole-derived ANTIFUNGAL AGENTS act through this mechanism.

Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP2C9.

Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP3A.

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.

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.

Use (kg; approx.) in Germany (2009): >1000；Consumption (g per capita; approx.) in Germany (2009): 0.0122；Excretion rate: 0.01；Calculated removal (%): 93

For topical application in the treatment of tinea pedis (athlete&rsquo;s foot), tinea cruris, and tinea corporis caused by <i>Trichophyton rubrum</i>, <i>Trichophyton mentagrophytes</i>, and <i>Epidermophyton floccosum</i>, in the treatment of cutaneous candidiasis (moniliasis), and in the treatment of tinea versicolor.