A-Migel

Approved Indications:

Topical Dermatologic Use:

• Tinea corporis (ringworm of the body)
• Tinea cruris (jock itch)
• Tinea pedis (athlete’s foot)
• Tinea versicolor (pityriasis versicolor)
• Cutaneous candidiasis caused by Candida albicans and other species
• Intertrigo with suspected or confirmed fungal involvement
• Seborrheic dermatitis (adjunctive antifungal use)

Vaginal Use:

• Vulvovaginal candidiasis (vaginal yeast infections), both uncomplicated and recurrent
• Vulvar pruritus associated with candidiasis

Oral and Oropharyngeal Use:

• Oropharyngeal candidiasis (oral thrush)
• Prevention of oral candidiasis in denture wearers and immunocompromised patients

Off-Label and Clinically Accepted Uses:

• Angular cheilitis (fungal-associated)
• Adjunct in mild onychomycosis (topical use)
• Candidal balanitis
• Prophylaxis of fungal infections in cancer patients, HIV-positive individuals, and those on immunosuppressive therapy (oral gel)

Formulations: Topical cream, powder, spray, vaginal cream/suppository, oral gel, and buccal tablet.

Topical Cream/Powder/Spray:

• Adults and Children >2 years:
  • Apply to affected skin twice daily (morning and evening)
  • Clean and dry the area before application
  • Duration:
  – Tinea pedis: 4 weeks
  – Tinea cruris/corporis: 2 weeks
  – Cutaneous candidiasis: 2–4 weeks

Vaginal Cream and Suppository:

• 100 mg suppository: Insert 1 per vagina at bedtime for 7 consecutive nights
• 200 mg suppository: Insert 1 per vagina at bedtime for 3 consecutive nights
• 2% vaginal cream: Apply 5 g intravaginally once daily for 7 days

Oral Gel (for Oropharyngeal Candidiasis):

• Adults: 5 mL (approx. 124 mg) oral gel 4 times daily, after meals
• Children >6 months: 1.25–2.5 mL 4 times daily
• Retain gel in the mouth for as long as possible before swallowing
• Duration: Minimum 7 days; continue for 2–3 days after symptoms resolve

Buccal Tablet:

• Apply one 50 mg buccal tablet to the upper gum region once daily
• Replace if tablet falls off within 6 hours; skip if it detaches after 6 hours

Special Populations:

• Elderly: No dose adjustment needed
• Renal/Hepatic Impairment: No adjustment required for topical or mucosal use

Miconazole nitrate is an imidazole antifungal that acts by inhibiting the biosynthesis of ergosterol, a vital component of fungal cell membranes. It blocks the cytochrome P450-dependent enzyme 14α-demethylase, leading to the accumulation of 14-methyl sterols and disruption of membrane permeability. This results in fungistatic or fungicidal activity depending on the concentration and fungal species. Additionally, miconazole exhibits limited antibacterial activity against Gram-positive bacteria, enhancing its utility in mixed infections.

• Absorption:
  • Topical/vaginal: Minimal systemic absorption through intact skin and mucosa
  • Oral gel/buccal tablet: Low systemic absorption through the oral mucosa
• Distribution: Highly protein-bound (>90%)
• Metabolism: Hepatic metabolism via oxidative pathways (non-CYP-specific)
• Elimination:
  • Mainly excreted in feces via biliary route
  • Minimal renal excretion
• Half-life: Approximately 24 hours for absorbed drug
• Onset: Symptomatic relief typically within 1–3 days of use

• Pregnancy:
  • FDA Category C
  • Topical and vaginal use show minimal systemic absorption
  • May be used when benefits outweigh potential risks, especially in the second and third trimesters
  • Avoid high-dose or prolonged use during early pregnancy
• Lactation:
  • Minimal systemic absorption; unlikely to excrete into breast milk in significant amounts
  • Considered compatible with breastfeeding
  • Avoid nipple application during lactation to prevent infant ingestion

• Primary Class: Antifungal agent
• Subclass: Imidazole antifungal (topical/mucosal use)

• Hypersensitivity to miconazole, imidazoles, or any formulation components
• Use in systemic fungal infections
• Ophthalmic use (not approved for eye application)
• Intravenous administration (not safe for systemic use)

• Hypersensitivity Reactions:
  • Rare anaphylaxis, rash, or contact dermatitis; discontinue immediately if observed
• Liver Disease:
  • Caution with prolonged oral use (e.g., oral gel); monitor liver function if necessary
• Warfarin Use:
  • Increased bleeding risk due to CYP2C9 inhibition; monitor INR closely
• Pediatrics:
  • Buccal tablets not recommended in children under 6 months due to choking risk
• Secondary Infections:
  • Long-term use may promote non-susceptible bacterial or fungal growth

Common (Local)

• Dermatologic (topical use):
  • Burning, stinging, maceration, redness, or irritation
• Vaginal use:
  • Vaginal burning, itching, irritation, or discharge
• Oral/buccal use:
  • Nausea, altered taste, dry mouth, oral irritation

Serious/Rare

• Hypersensitivity (urticaria, angioedema, anaphylaxis)
• Stevens-Johnson syndrome (very rare, mostly with oral gel misuse)
• Hepatotoxicity (rare and usually dose-related in oral mucosal forms)

Timing and Severity

• Local reactions appear early and are usually mild
• Serious effects are rare and typically dose- or duration-dependent

• Warfarin:
  • Miconazole inhibits CYP2C9 → increased warfarin levels and bleeding risk
  • INR should be closely monitored
• Oral Hypoglycemics (e.g., sulfonylureas):
  • May enhance hypoglycemic effects
  • Monitor blood glucose levels
• CYP450 Interactions:
  • Inhibits CYP2C9 and CYP3A4
  • Use caution with drugs metabolized via these enzymes (e.g., phenytoin, statins, certain benzodiazepines)
• Alcohol and Food:
  • No known interactions for topical, buccal, or vaginal use

• CDC and IDSA Guidelines:
  • Continue to recommend miconazole as first-line treatment for uncomplicated vulvovaginal candidiasis and superficial fungal infections
• FDA Safety Alerts:
  • Ongoing monitoring of interaction with warfarin even from non-oral routes
• Formulation Updates:
  • Mucoadhesive buccal tablets approved for enhanced treatment adherence in oropharyngeal candidiasis
• EMA/WHO Recommendations:
  • Support continued use in candidiasis prevention in immunocompromised patients

• Topical Cream/Ointment/Powder/Spray:
  • Store at 15°C to 30°C (59°F to 86°F)
  • Protect from moisture and light
  • Keep tightly closed; do not freeze
• Vaginal Suppositories and Creams:
  • Store at 20°C to 25°C (68°F to 77°F)
  • Avoid excessive heat; keep in original container
• Oral Gel and Buccal Tablets:
  • Store at below 25°C (77°F)
  • Do not refrigerate or freeze
  • Discard unused product 30 days after opening
• Handling Precautions:
  • Use clean hands or applicators
  • Avoid contact with eyes
  • Do not use past expiration date