Merck Manual

Please confirm that you are a health care professional

honeypot link

Antifungal Medications


Paschalis Vergidis

, MD, MSc, Mayo Clinic College of Medicine & Science

Reviewed/Revised Sep 2023
Topic Resources

Medications for systemic antifungal treatment include the following (see also table ):

  • Amphotericin B (and its lipid formulations)

  • Various azole derivatives (fluconazole, isavuconazonium [also referred to as isavuconazole], itraconazole, posaconazole, and voriconazole)

  • Echinocandins (anidulafungin, caspofungin, and micafungin)

  • Flucytosine

Amphotericin B, an effective but relatively toxic medication, has long been the mainstay of antifungal therapy for invasive and serious mycoses. However, newer potent and less toxic triazoles and echinocandins are now often recommended as first-line drugs for many invasive fungal infections. These drugs have markedly changed the approach to antifungal therapy, sometimes even allowing oral treatment of chronic mycoses.


Amphotericin B

Amphotericin B has been the mainstay of antifungal therapy for invasive and serious mycoses, but other antifungals (eg, fluconazole, voriconazole, posaconazole, the echinocandins) are now considered first-line drugs for many of these infections. Although amphotericin B does not have good cerebrospinal fluid penetration, it is still effective for certain mycoses such as cryptococcal meningitis Cryptococcal meningitis Subacute meningitis develops over days to a few weeks. Chronic meningitis lasts ≥ 4 weeks. Possible causes include fungi, Mycobacterium tuberculosis, rickettsiae, spirochetes, Toxoplasma... read more Cryptococcal meningitis .


There are 2 formulations of amphotericin B:

  • Deoxycholate (standard)

  • Lipid-based

The standard formulation, amphotericin B deoxycholate, must always be given in 5% D/W because salts can precipitate the drug. It is usually given over 2 to 3 hours, although more rapid infusions over 20 to 60 minutes can be used in selected patients. However, more rapid infusions usually have no advantage.

Many patients have chills, fever, nausea, vomiting, anorexia, headache, and, occasionally, hypotension during and for several hours after an infusion. Amphotericin B may also cause chemical thrombophlebitis when given via peripheral veins; a central venous catheter may be preferable. Pretreatment with acetaminophen or nonsteroidal anti-inflammatory drugs is often used; if these medications are ineffective, hydrocortisone 25 to 50 mg or diphenhydramine 25 mg is sometimes added to the infusion or given as a separate IV bolus. Often, hydrocortisone can be tapered and omitted during extended therapy. Severe chills and rigors can be relieved or prevented by meperidine 50 to 75 mg IV.

Several lipid vehicles reduce the toxicity of amphotericin B (particularly nephrotoxicity and infusion-related symptoms). Two preparations are available:

  • Amphotericin B lipid complex

  • Liposomal amphotericin B

Lipid formulations are preferred over conventional amphotericin B because they cause fewer infusion-related symptoms and less nephrotoxicity.

Adverse effects

The main adverse effects of amphotericin B are

  • Nephrotoxicity (most common)

  • Hypokalemia

  • Hypomagnesemia

  • Bone marrow suppression

Renal impairment is the major toxic risk of amphotericin B therapy. Serum creatinine and blood urea nitrogen (BUN) should be monitored before treatment and at regular intervals during treatment: several times/week for the first 2 to 3 weeks, then 1 to 4 times/month as clinically indicated.

Amphotericin B is unique among nephrotoxic antimicrobials because it is not eliminated appreciably via the kidneys and does not accumulate as renal failure worsens. Nevertheless, dosages should be lowered or a lipid formulation should be used instead if serum creatinine rises to > 2.0 to 2.5 mg/dL (> 177 to 221 micromol/L) or BUN rises to > 50 mg/dL (> 18 millimole/L). Acute nephrotoxicity can be reduced by aggressive IV hydration with saline before amphotericin B infusion; at least 1 L of normal saline should be given before amphotericin B infusion.

Mild to moderate renal function abnormalities induced by amphotericin B usually resolve gradually after therapy is completed. Permanent damage occurs primarily after prolonged treatment; after > 4 g total dose, approximately 75% of patients have persistent renal insufficiency.

Amphotericin B also may blunt the erythropoietin response and cause anemia. Hepatotoxicity or other untoward effects are unusual.

Azole Antifungals

Azoles block the synthesis of ergosterol, an important component of the fungal cell membrane. They can be given orally to treat chronic mycoses. The first such oral medication, ketoconazole, has been supplanted by more effective, less toxic triazole derivatives, such as fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazonium.

Drug interactions can occur with all azoles but are less likely with fluconazole. The drug interactions mentioned below are not intended as a complete listing; clinicians should refer to a specific drug interaction reference before using azole antifungals (see also the Antifungal Drug Interactions Database).

Pearls & Pitfalls

  • Drug interactions are common with azole antifungals; review all concurrent medications before prescribing them.


This water-soluble drug is absorbed almost completely after an oral dose. Fluconazole is excreted largely unchanged in urine and has a half-life of > 24 hours, allowing single daily doses. It has high penetration into cerebrospinal fluid (CSF) ( 70% of serum levels) and has been especially useful in treating cryptococcal meningitis Cryptococcal meningitis Subacute meningitis develops over days to a few weeks. Chronic meningitis lasts ≥ 4 weeks. Possible causes include fungi, Mycobacterium tuberculosis, rickettsiae, spirochetes, Toxoplasma... read more Cryptococcal meningitis and coccidioidal meningitis. It is also one of the first-line drugs for treatment of candidemia in nonneutropenic patients.

Doses of fluconazole range from 200 to 400 mg orally once a day to as high as 800 mg once a day for Candida glabrata infection and coccidioidal meningitis. Daily doses of 1000 mg have been given and have acceptable toxicity. Of note, Pichia kudriavzevii (Candida krusei) is inherently resistant to fluconazole.

Adverse effects that occur most commonly with fluconazole are gastrointestinal (GI) discomfort and rash. More severe toxicity is unusual, but the following have occurred: hepatic necrosis, Stevens-Johnson syndrome, anaphylaxis, alopecia, and, when taken for long periods of time during the first trimester of pregnancy, congenital fetal anomalies.

Drug interactions occur less often with fluconazole than with other azoles. However, fluconazole sometimes elevates serum levels of calcium channel blockers, cyclosporine, rifabutin, phenytoin, tacrolimus, and warfarin-type oral anticoagulants. Rifampin may lower fluconazole blood levels.


Itraconazole has become the standard treatment for lymphocutaneous sporotrichosis Sporotrichosis Sporotrichosis is a cutaneous infection caused by the saprophytic mold Sporothrix schenckii. Pulmonary and hematogenous involvement is uncommon. Symptoms are cutaneous nodules that spread... read more Sporotrichosis as well as for mild or moderately severe histoplasmosis Histoplasmosis Histoplasmosis is a pulmonary and hematogenous disease caused by Histoplasma capsulatum; it is often chronic and usually follows an asymptomatic primary infection. Symptoms are those... read more Histoplasmosis , blastomycosis Blastomycosis Blastomycosis is a pulmonary disease caused by inhaling spores of the dimorphic fungus Blastomyces dermatitidis. Occasionally, the fungi spread hematogenously, causing extrapulmonary... read more Blastomycosis , and paracoccidioidomycosis Paracoccidioidomycosis Paracoccidioidomycosis is progressive mycosis of the lungs, skin, mucous membranes, lymph nodes, and internal organs caused by Paracoccidioides brasiliensis. Symptoms are skin ulcers... read more Paracoccidioidomycosis . It is also effective for chronic pulmonary aspergillosis, coccidioidomycosis Coccidioidomycosis Coccidioidomycosis is caused by the fungi Coccidioides immitis and C. posadasii; it usually occurs as an acute, benign, asymptomatic or self-limited respiratory infection. The... read more Coccidioidomycosis , and certain types of chromoblastomycosis Chromoblastomycosis Chromoblastomycosis is a specific type of cutaneous infection caused by one of several species of dematiaceous (pigmented) fungi. Symptoms are ulcerating nodules on exposed body parts. Diagnosis... read more Chromoblastomycosis . Despite poor CSF penetration, itraconazole can be used to treat some types of fungal meningitis, but it is not the drug of choice. Because of its high lipid solubility and protein binding, itraconazole blood levels tend to be low, but tissue levels are typically high. Drug levels are negligible in urine and CSF. Use of itraconazole has declined as use of voriconazole and posaconazole has increased.

Adverse effects of itraconazole with doses of up to 400 mg/day most commonly are GI, but a few men have reported erectile dysfunction, and higher doses may cause hypokalemia, hypertension, and peripheral edema. Other reported adverse effects include allergic rash, hepatitis, and hallucinations. A U.S. Food and Drug Administration boxed warning for heart failure has been issued.

Drug and food interactions can be significant. When the capsule form is used, acidic drinks (eg, cola, acidic fruit juices) or foods (especially high-fat foods) improve absorption of itraconazole from the GI tract. However, absorption may be reduced if itraconazole is taken with prescription or over-the-counter medications used to lower gastric acidity.

Several medications, including rifampin, rifabutin, didanosine, phenytoin, and carbamazepine, may decrease serum itraconazole levels.

Itraconazole also inhibits metabolic degradation of other medications, elevating blood levels with potentially serious consequences. Serious, even fatal cardiac arrhythmias may occur if itraconazole is used with cisapride (not available in the United States) or some antihistamines (eg, terfenadine, astemizole, perhaps loratadine). Rhabdomyolysis has been associated with itraconazole-induced elevations in blood levels of cyclosporine or statins. Itraconazole may increase the serum concentration of certain medications (eg, tacrolimus, warfarin, digoxin) and therapeutic drug monitoring is recommended when these medications are used with itraconazole.

A new formulation of itraconazole (SUBA-itraconazole, for SUper BioAvailable) has improved bioavailability without the need for an acidic environment in the stomach. SUBA-itraconazole is taken with food and can be used to treat histoplasmosis, blastomycosis, and aspergillosis. Its dosage is different from other forms of itraconazole.


This broad-spectrum triazole is available as a tablet and an IV formulation. It is considered the treatment of choice for Aspergillus infections (aspergillosis Aspergillosis Aspergillosis is an opportunistic infection that usually affects the lower respiratory tract and is caused by inhaling spores of the filamentous fungus Aspergillus, commonly present in... read more Aspergillosis ) in immunocompetent and immunocompromised hosts. Voriconazole can also be used to treat Scedosporium apiospermum and Fusarium infections. Additionally, this medication is effective in candidal esophagitis and invasive candidiasis Candidiasis Candidiasis is infection by Candida species (most often C. albicans), manifested by mucocutaneous lesions, fungemia, and sometimes focal infection of multiple sites. Symptoms depend... read more Candidiasis , although it is not usually considered a first-line treatment; it has activity against a broader spectrum of Candida species than does fluconazole.

Adverse effects that must be monitored for include hepatotoxicity, visual disturbances (common), hallucinations, and dermatologic reactions (eg, photosensitivity). Voriconazole can prolong the QT interval.

Drug interactions are numerous, notably with certain immunosuppressants used after organ transplantation.


The triazole posaconazole is available as an oral suspension, a tablet, and an IV formulation. Delayed-release tablets are the preferred formulation because of improved oral bioavailability. This drug is highly active against yeasts and molds and effectively treats various opportunistic mold infections, such as those due to dematiaceous (dark-walled) fungi (eg, Cladophialophora species). It is effective against many of the species that cause mucormycosis Mucormycosis Mucormycosis refers to infection caused by diverse fungal organisms in the order Mucorales, including those in the genera Rhizopus, Rhizomucor, and Mucor. Symptoms of rhinocerebral... read more Mucormycosis . Posaconazole can also be used as antifungal prophylaxis in patients with neutropenia with hematologic malignancies and in bone marrow transplant recipients.

Adverse effects of posaconazole, as for other triazoles, include a prolonged QT interval and hepatitis.

Drug interactions occur with many medications, including rifabutin, rifampin, statins, and various immunosuppressants.


Adverse effects of isavuconazonium include GI upset and hepatitis; the QT interval may decrease.

Drug interactions occur with many medications.


Oteseconazole is an oral, novel azole antifungal that is used for the treatment of recurrent vulvovaginal candidiasis.

Adverse effects of oteseconazole include headache and nausea.

Drug interactions occur with rosuvastatin.


Echinocandins are water-soluble lipopeptides that inhibit glucan synthase. They are available only in an IV formulation. Their mechanism of action is unique among antifungals; echinocandins target the fungal cell wall, making them attractive because they lack cross-resistance with other drugs and their target is fungal and has no mammalian counterpart. Drug levels in urine and CSF are not significant.

Echinocandins available in the United States are anidulafungin, caspofungin micafungin, and rezafungin. There is little evidence to suggest that one is better than the other, but anidulafungin appears to interact with fewer medications than the others.

The dose of caspofungin needs to be adjusted in patients with severe hepatic insufficiency.

Anidulafungin is not metabolized by the liver but is eliminated by slow, spontaneous degradation. Dose adjustment for hepatic insufficiency is not required for anidulafungin.

Adverse effects of echinocandins include hepatitis and rash.


Major adverse effects of flucytosine are bone marrow suppression (thrombocytopenia and leukopenia), hepatotoxicity, and enterocolitis; the degree of bone marrow suppression is proportional to serum levels.

Because flucytosine is cleared primarily by the kidneys, blood levels rise if nephrotoxicity develops during concomitant use with amphotericin B, particularly when amphotericin B is used in doses > 0.4 mg/kg/day. Flucytosine serum levels should be monitored, and the dosage should be adjusted to keep levels between 40 and 90 mcg/mL. Complete blood count and renal and liver tests should be done twice/week. If blood levels are unavailable, therapy is begun at 25 mg/kg 4 times a day, and dosage is decreased if renal function deteriorates.

Drugs Mentioned In This Article

Drug Name Select Trade
Amphocin, Fungizone
7T Gummy ES, Acephen, Aceta, Actamin, Adult Pain Relief, Anacin Aspirin Free, Aphen, Apra, Children's Acetaminophen, Children's Pain & Fever , Children's Pain Relief, Comtrex Sore Throat Relief, ED-APAP, ElixSure Fever/Pain, Feverall, Genapap, Genebs, Goody's Back & Body Pain, Infantaire, Infants' Acetaminophen, LIQUID PAIN RELIEF, Little Fevers, Little Remedies Infant Fever + Pain Reliever, Mapap, Mapap Arthritis Pain, Mapap Infants, Mapap Junior, M-PAP, Nortemp, Ofirmev, Pain & Fever , Pain and Fever , PAIN RELIEF , PAIN RELIEF Extra Strength, Panadol, PediaCare Children's Fever Reducer/Pain Reliever, PediaCare Children's Smooth Metls Fever Reducer/Pain Reliever, PediaCare Infant's Fever Reducer/Pain Reliever, Pediaphen, PHARBETOL, Plus PHARMA, Q-Pap, Q-Pap Extra Strength, Silapap, Triaminic Fever Reducer and Pain Reliever, Triaminic Infant Fever Reducer and Pain Reliever, Tylenol, Tylenol 8 Hour, Tylenol 8 Hour Arthritis Pain, Tylenol 8 Hour Muscle Aches & Pain, Tylenol Arthritis Pain, Tylenol Children's, Tylenol Children's Pain+Fever, Tylenol CrushableTablet, Tylenol Extra Strength, Tylenol Infants', Tylenol Infants Pain + Fever, Tylenol Junior Strength, Tylenol Pain + Fever, Tylenol Regular Strength, Tylenol Sore Throat, XS No Aspirin, XS Pain Reliever
A-Hydrocort, Ala-Cort, Ala-Scalp, Alkindi, Anucort-HC, Anumed-HC, Anusol HC, Aquaphor Children's Itch Relief, Aquaphor Itch Relief, Balneol for Her, Caldecort , Cetacort, Colocort , Cortaid, Cortaid Advanced, Cortaid Intensive Therapy, Cortaid Sensitive Skin, CortAlo, Cortef, Cortenema, Corticaine, Corticool, Cortifoam, Cortizone-10, Cortizone-10 Cooling Relief, Cortizone-10 External Itch Relief, Cortizone-10 Intensive Healing, Cortizone-10 Plus, Cortizone-10 Quick Shot, Cortizone-5 , Dermarest Dricort, Dermarest Eczema, Dermarest Itch Relief, Encort, First - Hydrocortisone, Gly-Cort , GRx HiCort, Hemmorex-HC, Hemorrhoidal-HC, Hemril , Hycort, Hydro Skin, Hydrocortisone in Absorbase, Hydrocortone, Hydroskin , Hydroxym, Hytone, Instacort, Lacticare HC, Locoid, Locoid Lipocream, MiCort-HC , Monistat Complete Care Instant Itch Relief Cream, Neosporin Eczema, NuCort , Nutracort, NuZon, Pandel, Penecort, Preparation H Hydrocortisone, Proctocort, Proctocream-HC, Procto-Kit, Procto-Med HC , Procto-Pak, Proctosert HC , Proctosol-HC, Proctozone-HC, Rectacort HC, Rectasol-HC, Rederm, Sarnol-HC, Scalacort, Scalpicin Anti-Itch, Solu-Cortef, Texacort, Tucks HC, Vagisil Anti-Itch, Walgreens Intensive Healing, Westcort
Aid to Sleep, Alka-Seltzer Plus Allergy, Aller-G-Time , Altaryl, Banophen , Benadryl, Benadryl Allergy, Benadryl Allergy Children's , Benadryl Allergy Dye Free, Benadryl Allergy Kapgel, Benadryl Allergy Quick Dissolve, Benadryl Allergy Ultratab, Benadryl Children's Allergy, Benadryl Children's Allergy Fastmelt, Benadryl Children's Perfect Measure, Benadryl Itch Stopping, Ben-Tann , Children's Allergy, Compoz Nighttime Sleep Aid, Diphedryl , DIPHEN, Diphen AF , Diphenhist, DiphenMax , Dytan, ElixSure Allergy, Genahist , Geri-Dryl, Hydramine, Itch Relief , M-Dryl, Nighttime Sleep Aid, Nytol, PediaCare Children's Allergy, PediaCare Nighttime Cough, PediaClear Children's Cough, PHARBEDRYL, Q-Dryl, Quenalin , Siladryl Allergy, Silphen , Simply Sleep , Sleep Tabs, Sleepinal, Sominex, Sominex Maximum Strength, Theraflu Multi-Symptom Strip, Triaminic Allergy Thin Strip, Triaminic Cough and Runny Nose Strip, Tusstat, Unisom, Uni-Tann, Valu-Dryl , Vanamine PD, Vicks Qlearquil Nighttime Allergy Relief, Vicks ZzzQuil Nightime Sleep-Aid
Demerol, Meperitab
Aluvea , BP-50% Urea , BP-K50, Carmol, CEM-Urea, Cerovel, DermacinRx Urea, Epimide-50, Gord Urea, Gordons Urea, Hydro 35 , Hydro 40, Kerafoam, Kerafoam 42, Keralac, Keralac Nailstik, Keratol, Keratol Plus, Kerol, Kerol AD, Kerol ZX, Latrix, Mectalyte, Nutraplus, RE Urea 40, RE Urea 50 , Rea Lo, Remeven, RE-U40, RYNODERM , U40, U-Kera, Ultra Mide 25, Ultralytic-2, Umecta, Umecta Nail Film, URALISS, Uramaxin , Uramaxin GT, Urea, Ureacin-10, Ureacin-20, Urealac , Ureaphil, Uredeb, URE-K , Uremez-40, Ure-Na, Uresol, Utopic, Vanamide, Xurea, X-VIATE
Extina, Ketodan, Kuric, Nizoral, Nizoral A-D, Xolegel
Cequa, Gengraf , Neoral, Restasis, Sandimmune, SangCya, Verkazia, Vevye
Dilantin, Dilantin Infatabs, Dilantin-125, Phenytek
Coumadin, Jantoven
Rifadin, Rifadin IV, Rimactane
Videx, Videx EC, Videx Pediatric
Carbatrol, Epitol , Equetro, Tegretol, Tegretol -XR
Alavert, Allergy Relief, Claritin, Claritin 24 Hour, Claritin Chewable, Claritin Hives Relief, Claritin Liqui-Gel, Claritin RediTabs, Clear-Atadine , Dimetapp Children's Non-Drowsy Allergy, QlearQuil All Day & All Night Allergy Relief, Quality Choice Allergy Relief Non-Drowsy, Tavist ND
Digitek , Lanoxicaps, Lanoxin, Lanoxin Pediatric
Crestor, Ezallor
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
quiz link

Test your knowledge

Take a Quiz!