Tetramix

• Approved Indications:
• Treatment of mixed bacterial, protozoal, fungal infections of the skin and mucous membranes accompanied by inflammatory conditions.
• Superficial dermatological infections involving susceptible aerobic Gram-negative and Gram-positive bacteria, anaerobic protozoa, and dermatophyte fungi.
• Management of infected eczema, dermatitis, and pyoderma with inflammatory symptoms.
• Secondary infections complicating fungal or protozoal skin diseases.
• Clinically Accepted Off-Label Uses:
• Mixed infections in wounds, ulcers, or burns with inflammatory signs.
• Resistant or complicated superficial skin infections requiring broad antimicrobial coverage.

• Adults and Adolescents (≥12 years):
• Apply a thin layer to the affected area once or twice daily as directed by a physician.
• Duration typically limited to up to 2 weeks to minimize adverse effects and resistance risk.
• Pediatrics (<12 years):
• Use only under strict medical supervision; safety and efficacy not well established.
• Elderly:
• Use with caution; monitor for local and systemic side effects.
• Special Populations:
• No specific dose adjustment necessary for renal or hepatic impairment due to topical use but use caution with extensive application.
• Administration Notes:
• Topical application only.
• Avoid contact with eyes, open wounds (except as directed), mucous membranes unless formulated for such use.
• Do not cover treated areas with occlusive dressings unless prescribed.

• Clobetasol Propionate: Acts as a potent glucocorticoid receptor agonist suppressing pro-inflammatory gene expression, reducing inflammation, vasodilation, and immune responses in affected skin.
• Ofloxacin: A fluoroquinolone antibiotic that inhibits bacterial DNA gyrase and topoisomerase IV enzymes, preventing DNA replication and transcription, resulting in bactericidal activity primarily against aerobic Gram-positive and Gram-negative bacteria.
• Ornidazole: A nitroimidazole derivative that enters protozoal and anaerobic bacterial cells and undergoes reductive activation, generating reactive nitro radicals that damage DNA and cellular components, leading to cell death.
• Terbinafine: An allylamine antifungal that inhibits squalene epoxidase, an enzyme essential for ergosterol synthesis in fungal cell membranes, causing ergosterol depletion, accumulation of toxic squalene, and fungal cell death.

Together, this combination targets inflammatory processes and broad-spectrum microbial pathogens including aerobic bacteria, anaerobic protozoa, and fungi.

• Absorption:
  Minimal systemic absorption from topical application; absorption may increase with damaged or inflamed skin.
• Distribution:
  Mainly localized at the site of application; systemic distribution negligible.
• Metabolism:
  Clobetasol propionate is metabolized hepatically if absorbed; ofloxacin, ornidazole, and terbinafine may undergo hepatic metabolism if absorbed systemically.
• Elimination:
  Excreted primarily via urine (ofloxacin, ornidazole) and feces (terbinafine); topical route limits systemic exposure.
• Half-life:
  Not clinically relevant due to topical administration.
• Onset of Action:
  Anti-inflammatory and antimicrobial effects typically begin within days of application.

• Pregnancy:
• Clobetasol: Category C.
• Ofloxacin and Ornidazole: Category C; terbinafine topical data limited.
• Use only if benefits outweigh potential risks.
• Systemic absorption minimal but caution advised.
• Lactation:
• Limited data; topical use suggests low risk.
• Avoid application on breasts during breastfeeding to prevent infant exposure.
• Caution: Use during pregnancy and lactation only under medical supervision.

• Primary Class: Combination topical agent: corticosteroid + antibiotic + antiprotozoal + antifungal
• Subclass:
• Clobetasol Propionate: High-potency corticosteroid
• Ofloxacin: Fluoroquinolone antibiotic
• Ornidazole: Nitroimidazole antiprotozoal/antibacterial
• Terbinafine: Allylamine antifungal

• Known hypersensitivity to clobetasol, ofloxacin, ornidazole, terbinafine, or formulation excipients.
• Viral infections of skin (e.g., herpes simplex, chickenpox).
• Tuberculous or syphilitic skin infections.
• Use on eyes or mucous membranes unless formulated for such.
• Severe hepatic or renal impairment (caution advised).
• Pregnancy and lactation unless benefit justifies risk.

• Avoid prolonged use (>2 weeks) to minimize risk of skin atrophy and systemic corticosteroid effects.
• Risk of local and systemic adverse reactions if applied to large areas or damaged skin.
• Monitor for hypersensitivity reactions, especially with ofloxacin and ornidazole components.
• Use cautiously in patients with history of tendon disorders (ofloxacin systemic risk) even though topical risk is minimal.
• Avoid occlusive dressings unless directed.
• Discontinue if skin irritation, worsening infection, or hypersensitivity occurs.

• Common: Local burning, itching, irritation, dryness.
• Less common: Skin atrophy, telangiectasia, folliculitis, secondary infections.
• Rare: Allergic contact dermatitis, photosensitivity reactions, systemic corticosteroid effects with misuse.
• Serious (rare): Hypersensitivity reactions, tendonitis or tendon rupture (very rare topical risk), superinfection.

• Minimal systemic interactions expected due to topical use.
• Avoid concomitant use with other topical corticosteroids or antibiotics without physician approval.
• Systemic absorption of fluoroquinolones may interact with antacids, warfarin, and other drugs metabolized by CYP enzymes, but unlikely with topical application.

• Emphasis on limiting duration of corticosteroid-antimicrobial combination use to 1–2 weeks.
• Increased awareness on antimicrobial resistance risks with broad-spectrum combinations.
• Updated guidance on avoiding use in pregnancy and lactation unless clearly needed.
• Recommendations to monitor patients for hypersensitivity and adverse local reactions.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from light, moisture, and freezing.
• Keep container tightly closed.
• Keep out of reach of children.