Antifungals are systemic or topical. Systemic antifungals treat systemic mycoses and are toxic to the host, so do not use them indiscriminately. Culture the fungus first to confirm the right drug, because the wrong drug exposes the patient to serious toxicity for no benefit. Topical antifungals treat mycoses of skin and mucous membranes; some systemic agents also come in topical form.
Antifungals: Generic and Brand Names
- Systemic Antifungals
- Azole Antifungals
- fluconazole (Diflucan)
- itraconazole (Sporanox)
- ketoconazole (Nizoral, Xolegel)
- terbinafine (Lamisil)
- voriconazole (VFend)
- Echinocandin Antifungals
- anidulafungin (Eraxis)
- caspofungin acetate (Cancidas)
- micafungin (Mycamine)
- Other systemic antifungals
- amphotericin B ( Abelcet, Amphotec)
- flucytosine (Ancobon)
- griseofulvin
- nystatin (Mycostatin, Nilstat)
- Topical Antifungals
- Azole Topical Antifungals
- butoconazole (Gynazole I)
- clotrimazole (lotrimin, Mycelex)
- ketoconazole (Extina, Xolegel)
- miconazole (Monistat, Fungoid)
- oxiconazole (Oxistat)
- sertaconazole nitrate (Ertaczo)
- sulfonazole (Exelderm)
- terbinafine (Lamisil)
- terconazole (Terazol)
- tioconazole (Monistat-1, Vagistat-1)
- Other topical antifungals
- ciclopirox (Loprox, Penlac Nail Lacquer)
- gentian violet
- naftifine (Naftin)
- tolnaftate (Aftate, Tinactin)
- undecylenic acid (Cruex, Desenex)
Azole Antifungals
Azoles treat systemic and topical fungal infections. They are less toxic than other antifungals but may also be less effective.
Therapeutic Action
Azoles either bind sterols to cause cell death or interfere with cell replication. Ketoconazole, fluconazole, and itraconazole block a sterol in the fungal wall, which means they can also block human steroids like testosterone and cortisol. Posaconazole, a newer drug, inhibits ergosterol synthesis so the fungus cannot form its cell wall. Terbinafine blocks ergosterol formation.
Indications
Azoles treat candidiasis, cryptococcal meningitis, systemic mycoses, and aspergillosis, among others.
By age group: children are more sensitive to antifungals, so expect more severe adverse reactions. Only fluconazole, ketoconazole, terbinafine, and griseofulvin have established pediatric doses. Keep topical agents off open or draining areas to prevent systemic absorption, and avoid occlusive dressings, including tight diapers, over affected areas. Adults use OTC antifungals heavily; drive home that these drugs can be very toxic and are justified only once the causative organism is identified. Pregnant and lactating women should use them only when benefits clearly outweigh the risks, women of childbearing age should use barrier contraceptives, and topical agents stay off open or draining areas. Older adults are more vulnerable to adverse effects, especially with hepatic or renal dysfunction, so lower the dose.
Pharmacokinetics
Here are the characteristic interactions of azoles and the body in terms of absorption, distribution, metabolism, and excretion:
| Route | Onset | Peak | Duration |
|---|---|---|---|
| Oral | Slow | 1-2 h | 2-4 d |
| IV | Rapid | 1 h | 2-4 d |
| Half-life (T1/2) | Metabolism | Excretion |
|---|---|---|
| 30 h | liver | kidney (urine) |
Contraindications and Cautions
Hepatic dysfunction: ketoconazole, fluconazole, posaconazole, and terbinafine can cause serious hepatic toxicity, so monitor for bone marrow suppression and GI and liver toxicity, particularly with posaconazole. Endocrine or fertility problems: ketoconazole is absolutely contraindicated because of its effects on these processes; fluconazole is an alternative but can cause liver and renal toxicity, so use caution. Pregnancy and lactation: it is unknown whether most azoles cross the placenta or enter breastmilk, though terbinafine is known to do both. Patients on QTc-prolonging drugs: voriconazole worsens the risk and can cause ergotism with ergot alkaloids.
Adverse Effects
Liver toxicity, and severe effects on a fetus or nursing infant.
Interactions
Ketoconazole and fluconazole strongly inhibit the CYP450 system, raising serum levels of cyclosporine, digoxin, oral hypoglycemics, warfarin, oral anticoagulants, and phenytoin. Itraconazole causes serious cardiac effects with statins, triazolam, midazolam, pimozide, and dofetilide. Posaconazole and voriconazole cause ergotism with ergot alkaloids.
Echinocandin Antifungals
Echinocandins include anidulafungin, caspofungin, and micafungin.
Therapeutic Action
Echinocandins inhibit glucan synthesis. Glucan is present in the fungal cell wall but not in human cell walls, so destroying it stops the fungal wall from forming.
Indications
Candidemia and other Candida infections, invasive aspergillosis in patients who do not respond to or cannot tolerate other therapies, and prophylaxis of Candida infection in hematopoietic stem cell transplant patients. An intravenous echinocandin (caspofungin, micafungin, or anidulafungin) is the CDC-recommended initial treatment for most adults with invasive candidiasis, including candidemia (CDC).
Pharmacokinetics
Here are the characteristic interactions of azoles and the body in terms of absorption, distribution, metabolism, and excretion:
Anidulafungin
| Route | Onset | Peak | Duration |
|---|---|---|---|
| Anidulafungin IV | Rapid | N/A | N/A |
| Half-life (T1/2) | Metabolism | Excretion |
|---|---|---|
| 40-50 h | liver | colon (feces) |
Caspofungin
| Route | Onset | Peak | Duration |
|---|---|---|---|
| Caspofungin IV | Rapid | N/A | N/A |
| Half-life (T1/2) | Metabolism | Excretion |
|---|---|---|
| 9-11 h, then 6-48 h, then 40-50 h | liver | kidney (urine) |
Micafungin
| Route | Onset | Peak | Duration |
|---|---|---|---|
| Micafungin IV | Rapid | N/A | N/A |
| Half-life (T1/2) | Metabolism | Excretion |
|---|---|---|
| 14-17 h | liver | kidney (urine) |
Contraindications and Cautions
Anidulafungin may cross the placenta and enter breastmilk; use caution with hepatic impairment. Caspofungin is embryotoxic in animal studies and enters breast milk. Micafungin should be used in pregnant and lactating patients only when benefits clearly outweigh the risks.
Adverse Effects
Hepatic toxicity, serious hypersensitivity reactions (particularly micafungin), and bone marrow depression.
Interactions
Concurrent cyclosporine with caspofungin is contraindicated.
Other Antifungal Agents
Other agents include amphotericin B, flucytosine, griseofulvin, and nystatin.
Therapeutic Action
These agents kill fungal cells (fungicidal) and prevent fungal reproduction (fungistatic). Amphotericin B binds sterols in the fungal cell wall and changes its permeability; it is very potent with many unpleasant adverse effects. Flucytosine is less toxic and alters the cell membrane of susceptible fungi to cause cell death, and griseofulvin acts much the same way. Nystatin binds sterols in the cell wall, changing permeability and letting cellular contents leak out.
Indications
Progressive, potentially fatal infections (justified despite the adverse effects), systemic infections caused by Candida or Cryptococcus, and various tinea infections caused by Trichophyton spp.
Pharmacokinetics
Here are the characteristic interactions of other antifungals and the body in terms of absorption, distribution, metabolism, and excretion:
Amphotericin B and flucytosine
| Route | Onset | Peak | Duration |
|---|---|---|---|
| Amphotericin B and flucytosine IV | Rapid | 2 h for flucytosine | N/A |
| Half-life (T1/2) | Metabolism | Excretion |
|---|---|---|
| 24 h, then 15 days | not well understood | kidney (urine) |
Griseofulvin
| Route | Onset | Peak | Duration |
|---|---|---|---|
| Griseofulvin PO | N/A | 4 h | N/A |
| Half-life (T1/2) | Metabolism | Excretion |
|---|---|---|
| 24 h | liver | kidney (urine) |
Contraindications and Cautions
Amphotericin B has been used successfully in pregnancy but with caution, and is contraindicated during lactation because of risk to the neonate. Flucytosine demands extreme caution in renal impairment; toxicity can occur at 100 mcg/mL. Nystatin should not be used in pregnancy or lactation because effects are unknown.
Adverse Effects
Headache and mild CNS changes (griseofulvin); hepatic and renal failure, nausea, vomiting, potentially severe diarrhea, anorexia, and weight loss; bone marrow suppression, rash, and dermatologic changes; and pain at the injection site with phlebitis or thrombophlebitis.
Interactions
Do not combine amphotericin B with nephrotoxic antibiotics, antineoplastics, cyclosporine, or corticosteroids because of the increased risk of severe renal toxicity.
Nursing Considerations (Systemic Antifungals)
Assess for the cautions and contraindications above (allergy to antifungals, liver and kidney dysfunction, pregnancy and lactation). Do a full physical (other medications, orientation and reflexes, skin color and lesions) for baseline. Culture the infected area to confirm the type and drug responsiveness of the fungus. Check renal and hepatic function tests and CBC for baseline organ function and to catch toxicity during therapy. Relevant nursing diagnoses include acute pain related to GI, CNS, and local drug effects, and disturbed sensory perception related to CNS effects.
Confirm culture and sensitivity to verify this is the drug of choice. Ensure the patient finishes the full course (chronic infection may take up to 6 months) for full benefit. Monitor IV sites for phlebitis or infiltration. Provide safety measures (side rails, ambulation assistance, antipyretics for fever and chills, temperature regulation) if CNS effects like confusion, disorientation, or numbness appear. Offer small, frequent, nutritious meals for severe GI upset, monitor nutritional status, and arrange dietary consultation as needed. Tell the patient to report sore throat, unusual bruising or bleeding, or yellowing of eyes and skin (possible hepatic toxicity), or severe nausea and vomiting that threatens nutrition and recovery. Teach the regimen for understanding and compliance. Evaluate by tracking resolution of the infection, watching for adverse effects (orientation and affect, nutritional state, skin, renal and hepatic function), confirming the patient can name the drug, its indication, and adverse effects to watch for, and monitoring compliance.
Topical Antifungals
Topical antifungals treat mycoses of skin and mucous membranes; some systemic agents have topical forms. The fungi causing these mycoses are dermatophytes.
Therapeutic Action
Topical antifungals alter the fungal cell's permeability, preventing replication and causing fungal death.
Indication
Local treatment of mycoses, including tinea infections.
Pharmacokinetics
Topical antifungals are not absorbed systemically. Pharmacokinetics is unknown.
Contraindications and Cautions
Known allergy to topical antifungals. Econazole can cause intense local burning and irritation, so discontinue it if these appear. Gentian violet stains skin and clothing bright purple and can be very toxic, so apply it only near the active lesion. Naftifine, oxiconazole, and sertaconazole should not be used longer than 4 weeks because of adverse effects and possible emergence of resistant strains; sulconazole should not be used longer than 6 weeks for the same reasons.
Adverse Effects
Local irritation, burning, rash, and swelling; nausea, vomiting, and hepatic dysfunction (especially as suppository or troche); and urinary frequency, burning, or changes in sexual activity related to local vaginal absorption.
Nursing Considerations (Topical Antifungals)
Assess for allergy to antifungals and do a full physical (other medications, skin color, temperature, and lesions) for baseline. Culture the infected area to confirm the type and responsiveness of the fungus. A relevant nursing diagnosis is acute pain related to local drug effects.
Confirm culture and sensitivity, and ensure the patient completes the full course. Teach correct administration by route: dissolve troches slowly in the mouth; insert vaginal suppositories, creams, and tablets high into the vagina and keep the patient recumbent for at least 10-15 minutes after insertion; gently rub topical creams and lotions into the affected area after cleansing with soap and water and patting dry, and avoid occlusive bandages. Tell the patient to stop the drug for a severe rash, especially with blisters, or for severe local irritation and pain, which may signal drug sensitivity or a worsening condition. Teach the regimen for understanding and compliance. Evaluate by tracking resolution of the infection, watching for adverse effects (rash, local irritation, burning), confirming the patient can name the drug, its indication, and adverse effects, and monitoring compliance.
Frequently Asked Questions
Why do antibiotics not work on fungal infections?
Fungal cell walls are built from chitin and polysaccharides, not the structures antibiotics target. Antifungals work on fungus-specific targets like ergosterol and glucan in the fungal cell wall, so the right drug class matters.
Which antifungal class is first-line for invasive candidiasis?
An intravenous echinocandin (caspofungin, micafungin, or anidulafungin) is the CDC-recommended initial treatment for most adults with invasive candidiasis, including candidemia. Echinocandins inhibit glucan synthesis, which human cells do not use, giving them a favorable safety profile.
Why culture the fungus before starting a systemic antifungal?
Systemic antifungals are toxic to the host, so confirming the organism prevents exposing the patient to serious toxicity for no benefit. Culturing also matters because antifungal resistance, including in Candida species, is increasing.
What is the main toxicity concern with azoles?
Hepatic toxicity. Ketoconazole, fluconazole, posaconazole, and terbinafine can cause serious liver injury, so monitor liver function. Azoles also strongly inhibit the CYP450 system, raising levels of drugs like warfarin, cyclosporine, digoxin, and phenytoin.
How should topical vaginal antifungals be administered?
Insert vaginal suppositories, creams, or tablets high into the vagina and keep the patient lying down for at least 10 to 15 minutes afterward. Avoid occlusive dressings, and stop the drug for severe rash, blisters, or intense local irritation.