Miconazole

Miconazole belongs to the pharmacological class of Azole Antifungal Derivatives

Miconazole has been approved to relieve symptoms and also for the treatment and maintenance of Oropharyngeal candidiasis, Vulvovaginal candidiasis, Tinea infections, Tinea pedis, Tinea corporis, Tinea cruris.

Miconazole exhibits various pharmacokinetic characteristics. When administered orally as a single 50 mg tablet to healthy volunteers, it leads to a mean maximum plasma concentration (Cmax) of 15.1 ± 16.2 mcg/mL, a mean area under the curve (AUC0-24) of 55.2 ± 35.1 mcg/mL, and a median time to reach maximum concentration (Tmax) of 7 hours (range 2.0-24.1). Absorption of topical miconazole into the systemic circulation is limited, as evidenced by low plasma concentrations in patients receiving topical applications. For instance, pediatric patients treated with miconazole ointment showed plasma concentrations mostly below 0.5 ng/mL. In the case of vaginal administration using a 1200 mg ovule, the mean Cmax was 10.71 ng/mL, the mean Tmax was 18.4 hours, and the mean AUC0-96 was 477.3 ng/mL. Miconazole has a large apparent volume of distribution in the body, with a calculated value of 95,546 L for the vaginal suppository and 10,911 L for the vaginal cream. It binds to human serum albumin, but the clinical significance of this interaction remains uncertain. Metabolically, miconazole undergoes hepatic metabolism without generating any active metabolites, and it is eliminated through both urine and feces, with less than 1% of unchanged miconazole excreted in urine.

The common side effects involved in using Miconazole are burning sensation, stinging feeling, swelling, irritation, redness, the appearance of pimple-like bumps, tenderness, or flaking of the treated skin.

Miconazole is available in the form of topical cream , topical suppository, topical gel, topical powder, and suppositories.

Miconazole belongs to the pharmacological class of Azole Antifungal Derivatives

Miconazole is an azole antifungal medication that is widely used to treat various conditions associated with Candida overgrowth. It possesses unique mechanisms of action compared to other azoles. One of its primary mechanisms involves inhibiting the activity of the CYP450 14α-lanosterol demethylase enzyme, resulting in the disruption of ergosterol production and alterations in cell membrane composition and permeability. This disruption leads to the leakage of cations, phosphates, and low molecular-weight proteins. Additionally, miconazole inhibits fungal peroxidase and catalase enzymes, leading to the generation of reactive oxygen species (ROS) within the fungal cells. The increased intracellular ROS triggers various downstream effects and eventually induces apoptosis. Another noteworthy effect of miconazole is its ability to elevate intracellular levels of farnesol, a molecule involved in quorum sensing of Candida. This prevents the transition from yeast to mycelial forms and inhibits the formation of biofilms, which are more resistant to antibiotics. Furthermore, farnesol acts as an inhibitor of drug efflux ABC transporters, such as Candida CaCdr1p and CaCdr2p, which enhances the effectiveness of azole drugs. Overall, these mechanisms contribute to the antifungal properties of miconazole against Candida infections.

Miconazole has been approved to relieve symptoms and also for the treatment and maintenance of Oropharyngeal candidiasis, Vulvovaginal candidiasis, Tinea infections, Tinea pedis, Tinea corporis, Tinea cruris.

When a single 50 mg miconazole tablet was orally administered to healthy volunteers, the average maximum plasma concentration (Cmax) observed was 15.1 ± 16.2 mcg/mL. The mean area under the curve (AUC0-24) was 55.2 ± 35.1 mcg*h/mL, indicating the extent of drug exposure over 24 hours. The median time taken to reach the maximum concentration (Tmax) was 7 hours, with a range of 2.0 to 24.1 hours.The administration of a 1200 mg miconazole vaginal ovule yielded a mean maximum plasma concentration (Cmax) of 10.71 ng/mL. The mean time to reach the maximum concentration (Tmax) was 18.4 hours, and the mean area under the curve (AUC0-96) was 477.3 ng*h/mL. These measurements provide information on the pharmacokinetics of miconazole following the use of a 1200 mg vaginal ovule.

Miconazole is found to be available in the form of topical cream, topical suppositories, topical gel, topical powder, and suppositories.

Miconazole can be used in the following treatment:

• Oropharyngeal candidiasis
• Vulvovaginal candidiasis
• Tinea infections
• Tinea pedis
• Tinea corporis
• Tinea cruris

Miconazole can help to relieve symptoms and also for the treatment and maintenance of Oropharyngeal candidiasis, Vulvovaginal candidiasis, Tinea infections, Tinea pedis, Tinea corporis, Tinea cruris.

Miconazole is approved for use in the following clinical indications:

• Oropharyngeal candidiasis
• Vulvovaginal candidiasis
• Tinea infections
• Tinea pedis
• Tinea corporis
• Tinea cruris

For mild oropharyngeal candidiasis, an alternative treatment option is available. This involves using a buccal tablet containing 50 mg of miconazole. The tablet should be applied to the upper gum region, specifically the canine fossa, once daily. The treatment duration typically ranges from 7 to 14 days.

Candidiasis, vulvovaginal:

• Combination Pack: Many products are available as a combination pack, including a suppository for vaginal instillation and a cream to relieve external symptoms. In cases of complicated infection or specific conditions, a longer treatment duration of up to 14 days may be necessary.
• Cream 2%: For intravaginal use, insert 1 applicatorful (~5 g) once daily at bedtime for 7 days. Additionally, it can be applied externally twice daily for 7 days if needed to alleviate itching and irritation.
• Cream 4%: For intravaginal use, insert 1 applicatorful (~5 g) once daily at bedtime for 3 days. It can also be applied externally twice daily for 7 days to address itching and irritation.
• Suppository 100 mg: For intravaginal use, insert 1 suppository once daily at bedtime for 7 days.
• Suppository 200 mg: For intravaginal use, insert 1 suppository once daily at bedtime for 3 days.
• Suppository 1.2 g: For intravaginal use, insert 1 suppository as a single dose at bedtime or during the day.

Tinea infections:

• Tinea corporis/tinea cruris (OTC labeling): Use topical aerosol powder (tinea corporis only), cream, ointment, powder, or solution. Apply to the affected and surrounding area(s) twice daily until clinical resolution, typically lasting 1 to 4 weeks.
• Tinea pedis (OTC labeling)/tinea manuum (off-label use): Use topical aerosol powder, aerosol solution, cream, ointment, powder, or solution. Apply to the affected and surrounding area(s) twice daily until 1 week after clinical resolution, usually for a total of 4 weeks.

Dietary restrictions related to the use of miconazole are not typically required. Miconazole is primarily used topically, such as in creams or suppositories, for localized treatment of fungal infections. Since the systemic absorption of miconazole from topical application is minimal, there are no specific dietary restrictions associated with its use.

Miconazole may be contraindicated under the following conditions:

• Prior hypersensitivity or allergic reactions to Miconazole are considered contraindications to its use.

General:

• Patients should consult a physician if vaginal pruritus or discomfort is occurring for the first time.
• Patients should seek medical attention if they experience fever, nausea, unexplained pain in the lower back, lower abdomen, or shoulder, or foul-smelling vaginal discharge.
• Discontinue medication if signs of irritation or sensitization occur.

Endocrine and Metabolism:

• Intractable candidiasis may be a symptom of unrecognized diabetes. Further urine/blood studies may be necessary.
• If unresponsive to therapy, repeat microbiological studies should be conducted to confirm the diagnosis and rule out other pathogens.

Sexual Health:

• Miconazole nitrate preparations can reduce the effectiveness of latex condoms and diaphragms.
• During therapy with MONISTAT1 and MONISTAT1 Combination Pack, the use of diaphragms and condoms is not recommended.

Reproduction:

• Condoms and diaphragms may be damaged and fail to prevent pregnancy or sexually transmitted diseases.

Function:

• Instruct the patient to refrain from intercourse during therapy.

The excretion of the drug in human milk is not known. Since many drugs are excreted in human milk, caution should be exercised.

Pregnancy:

Teratogenic Effects - Category C

Recommendations for pregnant patients include exercising caution when using the vaginal applicator for the ovule or, alternatively, inserting the ovule manually. Follow-up reports on infants born to pregnant patients who participated in clinical evaluations of Miconazole Nitrate 100 mg Suppositories and Miconazole Nitrate 2% Cream indicated no complications or adverse effects associated with the use of these medications. However, it should be noted that miconazole nitrate is absorbed in small amounts from the vagina, and therefore Miconazole vaginal preparations should only be used by pregnant or nursing women if deemed essential by a physician for the patient's well-being.

While there are no specific food warnings related to the use of miconazole, it is generally recommended to avoid consuming grapefruit or grapefruit juice when taking certain medications. This is because grapefruit can interfere with the metabolism of certain drugs, including miconazole, and may alter their effectiveness or increase the risk of side effects.

The adverse reactions related to Miconazole can be categorized as follows:

Common:

• Burning
• Stinging
• Irritation
• Redness

Less common:

• Swelling
• Pimple-like bumps
• Tenderness
• Flaking of the treated skin

Rare:

• Allergic reactions (rash, itching, hives)
• Difficulty breathing

The following are the side effects involving Miconazole:

• Sensation of burning
• Stinging feeling
• Swelling
• Irritation
• Redness
• Appearance of pimple-like bumps
• Tenderness
• Flaking of the treated skin

Pregnancy:

Teratogenic Effects - Category C

Recommendations for pregnant patients include exercising caution when using the vaginal applicator for the ovule or, alternatively, inserting the ovule manually. Follow-up reports on infants born to pregnant patients who participated in clinical evaluations of Miconazole Nitrate 100 mg Suppositories and Miconazole Nitrate 2% Cream indicated no complications or adverse effects associated with the use of these medications. However, it should be noted that miconazole nitrate is absorbed in small amounts from the vagina, and therefore Miconazole vaginal preparations should only be used by pregnant or nursing women if deemed essential by a physician for the patient's well-being.

Lactation:

The excretion of the drug in human milk is not known. Since many drugs are excreted in human milk, caution should be exercised.

Pediatric:

Pediatric data under the age of 12 is not available.

Physicians should be knowledgeable as well as vigilant about the treatment and identification of overdosage of Miconazole.

To date, there have been no reported cases of overdosage of Miconazole nitrate in humans. However, studies conducted on mice, rats, guinea pigs, and dogs have shown oral LD50 values of 578.1 mg/kg, greater than 640 mg/kg, 275.9 mg/kg, and greater than 160 mg/kg, respectively.

Pharmacodynamics

Miconazole is an azole antifungal that primarily functions by inhibiting a specific demethylase within the CYP450 complex. It is commonly applied topically, and its systemic absorption is minimal, resulting in limited adverse reactions for patients, mostly consisting of hypersensitivity and rare cases of anaphylaxis. When using intravaginal miconazole products, patients are advised not to rely solely on them for contraception or protection against sexually transmitted infections. It is recommended to use additional contraceptive methods as appropriate. Concurrent use of tampons with intravaginal miconazole products should be avoided to prevent potential interactions or reduced efficacy. It is important to consult healthcare professionals or refer to the prescribing information for specific guidance on miconazole use and associated precautions.

Pharmacokinetics

Absorption

● Oral administration of a single 50 mg miconazole tablet in healthy volunteers resulted in a mean maximum plasma concentration (Cmax) of 15.1 ± 16.2 mcg/mL, a mean area under the curve (AUC0-24) of 55.2 ± 35.1 mcg*h/mL, and a median time to reach maximum concentration (Tmax) of 7 hours (range 2.0-24.1). Plasma concentrations ranged from 0.5 to 0.83 mcg/mL in these patients.

● Topical miconazole has poor absorption into the systemic circulation. In pediatric patients aged 1-21 months receiving 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 a slightly higher concentration observed in the remaining patients.

● Administration of a 1200 mg miconazole vaginal ovule resulted in a mean Cmax of 10.71 ng/mL, a mean Tmax of 18.4 hours, and a mean AUC0-96 of 477.3 ng*h/mL.

Volume of Distribution

The calculated apparent volume of distribution for a 1200 mg miconazole vaginal suppository was 95,546 L, while a 100 mg vaginal cream yielded an apparent volume of distribution of 10,911 L.

Protein Binding

In vitro data suggests that miconazole binds to human serum albumin, but the clinical significance of this observation is unclear.

Metabolism

Miconazole is metabolized in the liver and does not produce any active metabolites.

Route of Elimination

Miconazole is eliminated from the body through both urine and feces, with less than 1% of unchanged miconazole being excreted in the urine.

There are some clinical studies of the drug Miconazole mentioned below:

• Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guidelines for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62(4):409-417. [PubMed 26810419]
• Stevens RE, Konsil J, Verrill SS, et al, "Bioavailability Study of a 1200 mg Miconazole Nitrate Vaginal Ovule in Healthy Female Adults," J Clin Pharmacol, 2002, 42(1):52-60. [PubMed 11808824]
• Weinstein A, Berman B. Topical treatment of common superficial tinea infections. Am Fam Physician. 2002;65(10):2095-2102. [PubMed 12046779]
• Young GL, Jewell D. Topical treatment for vaginal candidiasis (thrush) in pregnancy. Cochrane Database Syst Rev. 2001;(4):CD000225. doi:10.1002/14651858.CD000225 [PubMed 11687074]
• Zeasorb AF (miconazole) [prescribing information]. Johnson City, TN: Crown Laboratories Inc; received December 2018.

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