What prescription antifungal medications are available for an adult patient with a persistent or severe fungal infection that is not responding to over-the-counter (OTC) treatments?

Prescription Antifungal Options Stronger Than OTC Treatments

For persistent or severe fungal infections not responding to over-the-counter treatments, oral fluconazole 100-200 mg daily for 7-14 days is the first-line prescription option for most superficial infections, while systemic or invasive infections require echinocandins (caspofungin, micafungin, or anidulafungin) or amphotericin B formulations. 1

Superficial Fungal Infections (Skin, Nails, Mucous Membranes)

Oral Azoles - First-Line for Most Superficial Infections

• Fluconazole 100-200 mg daily is the most commonly prescribed oral antifungal for moderate-to-severe superficial infections including candidiasis, with treatment duration of 7-14 days depending on severity 1, 2
• Itraconazole 200 mg daily is an alternative oral azole with broader spectrum activity against dermatophytes and yeasts, particularly useful for nail infections 1
• For fluconazole-refractory disease, itraconazole solution 200 mg once daily OR posaconazole suspension 400 mg twice daily for 3 days then 400 mg daily for up to 28 days are recommended 1, 3

Oral Allylamines - Fungicidal Option

• Terbinafine is fungicidal (actually kills fungi rather than just stopping growth) and preferred for dermatophyte infections with treatment as short as 1 week, offering higher cure rates than fungistatic azoles 4
• Allylamines work less well for yeast infections like Candida, where azoles remain preferred 4

Specific Clinical Scenarios

For oropharyngeal candidiasis (thrush):

• Mild disease: Clotrimazole troches 10 mg 5 times daily for 7-14 days 1
• Moderate-to-severe: Oral fluconazole 100-200 mg daily for 7-14 days 1
• Refractory cases: Itraconazole solution 200 mg daily or posaconazole 400 mg twice daily 1

For esophageal candidiasis:

• Fluconazole 200-400 mg daily for 14-21 days until clinical improvement 1

For intertriginous candidiasis (skin folds):

• Moderate-to-severe: Oral fluconazole 100-200 mg daily for 7-14 days, particularly in diabetic patients 2

Invasive or Systemic Fungal Infections

Echinocandins - Preferred for Severe Candida Infections

These are the strongest antifungals for invasive candidiasis and are administered intravenously:

• Caspofungin: 70 mg loading dose, then 50 mg daily 1
• Micafungin: 100 mg daily 1
• Anidulafungin: 200 mg loading dose, then 100 mg daily 1

Echinocandins are fungicidal against Candida species and have minimal adverse effects, making them preferred for moderately severe to severe illness 1, 5

Amphotericin B Formulations - Broadest Spectrum

For life-threatening or resistant infections:

• Amphotericin B deoxycholate: 0.5-1 mg/kg daily IV for invasive candidiasis 1
• Lipid formulations of amphotericin B: 3-5 mg/kg daily, better tolerated than conventional amphotericin 1
• Amphotericin B has the broadest antifungal spectrum but significant toxicity including kidney damage 6

Voriconazole - For Aspergillus and Mold Infections

• Voriconazole: 400 mg (6 mg/kg) twice daily for 2 doses, then 200 mg (3 mg/kg) twice daily 1
• Voriconazole has broad-spectrum activity against yeasts and molds including Aspergillus species 5
• Preferred when additional coverage for molds is desired beyond Candida 1
• Monitor for visual disturbances and liver enzyme elevations 5

Posaconazole - Broadest Azole Spectrum

• Posaconazole is the only azole with activity against zygomycete fungi (mucormycosis) 5
• Available as delayed-release tablets 100 mg or oral suspension 3
• Used for prophylaxis in severely immunocompromised patients and treatment of refractory infections 3

Important Clinical Considerations

Drug Selection Algorithm

Choose based on:

1. Infection severity: Mild = topical or oral azoles; Moderate-to-severe = oral fluconazole; Life-threatening = IV echinocandins or amphotericin B 1, 2
2. Fungal species: Candida = echinocandins or fluconazole; Aspergillus = voriconazole; Dermatophytes = terbinafine; Mucormycosis = posaconazole or amphotericin B 5, 7
3. Prior azole exposure: If recent azole use, choose echinocandin to avoid resistance 1
4. Site of infection: CNS/eye infections require fluconazole, voriconazole, or 5-flucytosine due to better penetration; echinocandins have inadequate CNS penetration 7

Common Pitfalls to Avoid

• Do not use fungistatic azoles for short treatment courses if patient compliance is uncertain; fungi recur more often when treatment is stopped early with fungistatic drugs versus fungicidal agents 4
• Avoid azoles in patients with recent azole prophylaxis due to resistance risk; use echinocandin instead 1
• Monitor for drug-drug interactions with azoles, particularly itraconazole, voriconazole, and posaconazole which interact with many medications including statins, immunosuppressants, and anticonvulsants 3, 7
• Therapeutic drug monitoring may be needed for itraconazole, voriconazole, or posaconazole due to variable absorption and metabolism 7
• Nail and hair follicle infections rarely respond to topical therapy alone; systemic oral treatment is required 4