The Ultimate Resource for Fungal and Yeast Infections

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Prescription Drugs For Treating Fungus, Yeast, And Candida Infections

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See the associated page “OVERVIEW OF ANTIFUNGAL PRESCRIPTION DRUGS” for a table summarizing the major points of the following discussion.


Due to the similarity of the cell membrane of fungus (ergosterol) and animals (cholesterol), there are few antifungal drugs that are safe for humans. Unfortunately, chemicals that can poke holes in a fungus can make your cells spill their guts as well. So, whereas there are dozens of prescription antibacterial drugs, the following table lists all ten antifungal drugs available for internal use. Continuing with the theme of this web site, the fungus focus of the following material is Candida.

As discussed on the Candida page, there is a distinct and important difference between a true systemic infection and an intestinal fungus overgrowth that has systemic effects. True systemic fungal infections in which a fungus is transported throughout the body by the bloodstream are extremely dangerous with a high mortality rate. Although they can occur in immune-competent people (healthy people), they most prevalently strike the immune-compromised (HIV/AIDS, cancer patients on chemotherapy, and organ transplant patients with chemically suppressed immune systems). The application of drugs for treatment of systemic fungal infections is the province of the infectious disease specialist.

The problem addressed by this web site is that, while there are such experts, there is little awareness or acknowledgment among the traditional medical community of the problem of fungus and Candida overgrowth in the intestines. The point of the following discussion is to help Candida victims understand their treatment options.


Clinical experience with AIDS patients demonstrates that, in general, improvement of unfavorable immune factors constitutes the major issue in the successful outcome of Candida infections.


The triazoles (fluconazole - Diflucan, voriconazole - Vfend, and itraconazole - Sporanox) are generally considered to be fungistatic agents, featuring lower toxicity than amphotericin-B and ketoconazole (Nizoral - the other principal azole). Of the imidazoles, ketoconazole is fungistatic, but clotrimazole is fungicidal; miconazole is fungistatic at lower dosages and fungicidal at higher dosages. The azoles primarily function by interfering with fungal growth -- in particular with the ability to build cell walls.

Hepatotoxicity (liver) may be common to all of them, and the potential for endocrine toxicities exists, particularly at high doses. If you are going to be on azole therapy your liver function must be monitored with blood tests, usually every 5 to 6 weeks. There are indicators for liver problems, and you should watch for those in between liver tests. These include itchy skin, abdominal cramps, dark stool and/or urine, and pain at the base of your ribs on the right side. If you have ever had liver problems, you may not be able to tolerate the azoles.

They are available in oral formulations and are more readily absorbed in an acidic gastric environment, so take with food. Antacids and H2-blockers like Zantac, Pepsid-AC, Tagamet, and so on, can inhibit their absorption. Azoles (especially ketoconazole and itraconazole) inhibit the metabolism of a lot of drugs, including Warfarin (Coumadin) and alprazolam (Xanax). Fluconazole and clotrimazole are used topically to treat vaginal yeast infections. Clotrimazole in the form of a troche (lozenge) is now considered to be the antifungal of choice to treat oral Candida infections in patients who are immunocompromised, including those with HIV infections. It is far better tasting than nystatin (Mycostatin).

In one recent review of published studies of the treatment of oral thrush, only ketoconazole and clotrimazole were found to be effective.


Fluconazole is generally quite well tolerated.  It is principally active against Candida and Cryptococcus. For most situations, fluconazole has become the drug of choice in the management of Candidemia and disseminated candidiasis. Studies have demonstrated that fluconazole at a dose of 400 mg/day is as efficacious as amphotericin-B. In addition, fluconazole has several advantages, which are lower nephrotoxicity (<2%) (kidney) and ease of use because of the high degree of bio-availability (GI tract absorption) and the long half-life of the drug. Fluconazole penetrates well into most body tissues and achieves excellent levels in the cerebrospinal fluid. Importantly, Difulcan is the only one of the azoles to effedtively pass the blood-brain barrier to reach fungus and yeast in the central nervous system.

Fluconazole is particularly noted for its lack of serious side effects and its compatibility with AZT (before fluconazole, AIDS patients had few if any options for dealing with fungal infections).

For most Candida infections the standard recommended dose is a loading dose at 800 mg of fluconazole the first day, followed by 400 mg/day for at least 2 weeks after a demonstrated negative blood culture or clinical signs of improvement. This treatment regimen can be utilized for infections due to C. albicans, C. tropicalis, C. parapsilosis, C. kefyr, C. dubliniensis, C. lusitaniae, and C. guilliermondi. Higher doses  are recommended for other than C. albicans. Candida krusei is intrinsically resistant to fluconazole, and resistance to fluconazole is common among strains of C. glabrata, with as many as 15% of isolates being completely resistant.

For oropharyngeal candidiasis, and other forms of mucocutaneous candidiasis, fluconazole is typically dosed at 50-150 mg/day. For invasive candidiasis, the commonly applied dose is 6 mg/kg/day, or 400 mg/day in the typical 70 kg (150 lb.) adult. Doses of 12 mg/kg (800 mg/day for a 150 lb. person) are not FDA-approved, but are used with increasing frequency due to the desire to achieve higher blood levels and thus extend the range of use of the drug. Even higher doses (up to 30 mg/kg in one report) have been used safely. Many doctors who understand Candida are prescribing dosages at these higher ranges of 800 mg per day and more, with some going as high as 2000 mg per day. Fluconazole is excreted by the kidneys, and the dose should be reduced in proportion to any reduction of kidney function.

Fluconazole may cause hepatotoxicity (liver), but is generally well tolerated.


Voriconazole is a new drug chemically related to fluconazole, having favorable activity against most Candida species. Voriconazole may be an effective alternative to Candida species resistant to fluconazole. Voriconazole was approved by FDA in May 2002 for primary treatment of acute invasive Aspergillosis and "salvage therapy" for some rare but serious fungal infections.

Voriconazole is generally considered to be a fungistatic agent against Candida. It may, however, be fungicidal against Aspergillus. Its enhanced activity against fluconazole-resistant Candida krusei and selected Candida glabrata is noteworthy. However, some isolates of Candida exhibit cross resistance to all azoles, including voriconazole.

Toxicity is demonstrated as dose-related, transient visual disturbances, skin rash and elevated hepatic enzyme levels. Visual disturbance is an interesting and extensively investigated side effect of voriconazole. Patients experiencing visual disturbance during voriconazole therapy describe it in various forms; brightness, blurring, light sensitivity, or some changes in color vision. Typically, these visual abnormalities, seen in around 30% of patients receiving voriconazole, start 30 minutes after the dose, and last about 30 minutes.


An important feature of itraconazole is its favorable in vitro activity against some of the fluconazole-resistant Candida strains. This property makes itraconazole a good candidate for treatment of systemic Candida infections. However, itraconazole does not improve on the general anti-Candida spectrum of fluconazole. Itraconazole is widely used for fungal nail infections.

Itraconazole is highly lipophilic (fat loving) with limited penetration into aqueous fluids such as spinal fluid. It tends to accumulate in skin, nails, and fatty tissues


Ketoconazole is now less commonly used in treatment of Candida infections due to the availability of more efficacious and less toxic azole compounds, with fluconazole being the preferred front-line choice. However, anecdotal and scientific information indicates that ketoconazole may be more effective, at least in some situations. According to one report: "In my case, 400 mg per day did nothing, but 400 mg of ketoconazole did." And, a 2003 study finds that only ketoconazole and clotrimazole were effective in treating oral candidiasis.

Oral ketoconazole is used at a dose of 200 to 400 mg/day in treatment of oral and chronic mucocutaneous candidiasis. The dose can be increased to 600-800 mg/day in patients not responding to regular doses. However, high doses carry the risk of high incidence of toxicity.

There are occasional adverse reactions to ketoconazole therapy, including nausea and vomiting, and hepatoxicity. Ketoconazole may decrease testosterone and cortisol levels, resulting in gynecomastia (breast development) and oligospermia (low sperm count) in men and menstrual irregularities in women.


Among the small list of available antifungal drugs, clotrimazole is one of the few that are fungicidal. Clotrimazole showed great activity as topical creams and is available over-the-counter under a variety of trade names, but serious side effects (such as anemia and thrombocytosis) arose from systemic administration. Even though it is well absorbed by the GI tract, much of the drug was lost through first-pass metabolism in the liver, and, due to its lipophilic nature, the drug would bind to proteins in the blood so that little was available to have its antifungal effect.

Clotrimazole is currently available for internal use in a 10 mg troche (lozenge) for oral thrush, to be dissolved slowly in the mouth, five times per day. One recent study indicates greater efficacy in a 50 mg dose.


Miconazole is fungistatic in lower doses, and fungicidal in higher doses against species of the genus Candida. Miconazole also inhibits several other genera of fungi, including dermatophytes and yeasts, as well as Gram-positive bacteria.

Miconazole is effective and generally well tolerated, but poorly absorbed in the GI tract. Miconazole had been used in an IV form to treat systemic fungal infections, however the IV form has been discontinued in the US by its manufacturer, Janssen, although it may be available in IV form in other countries. In some countries (but not the US), miconazole is available in an oral gel for treatment of oral thrush. By some views, miconazole oral gel replaces Nystatin as the preferred agent for the treatment of oral candidiasis, although the clotrimazole troche is also very effective.

There are anecdotal reports of some MD's treating Candida who prescribe an oral formulation of miconazole to be prepared by a compounding pharmacy. See our page on SCORING SPECIAL Rx DRUGS for more information about compounding pharmacies.

There are at least two safety concerns regarding miconazole: there is a potential interaction with the blood thinner Warfarin (Coumadin) that could cause bleeding or bruising; and, there is a potential interaction between oral miconazole and oral hypoglycemic agents used by diabetics to lower blood sugar, leading to severe hypoglycemia. There are indications that these interactions may occur from systemically absorbed miconazole due to topical and vaginal treatment.


Flucytosine is sometimes referred to as 5-F or 5-FU, an abbreviation of its chemical name. Although now less commonly used against Candida infections, flucytosine often has excellent activity against Candida. It is readily soluble in water, and thus may have application in treating fungal infections not easily reached by the other lipid-based antifungal drugs.

Fungi and yeasts frequently develop resistance to flucytosine, so it is rarely administered by itself. Flucytosine appears to interact synergistically with amphotericin-B and so it is almost always administered with amphotericin-B or fluconazole, or with both amphotericin-B and fluconazole as combination therapy. It is believed that AmB damages the fungal cell wall sufficiently to allow more 5-F in, expediting its desired effect.

As 5-F is also an anticancer drug, the side effects can be rather strong.  It can cause bone marrow depression (including leukopenia and anemia), GI disturbances (such as nausea, vomiting, and diarrhea) , hepatotoxicity, and CNS (Central Nervous System) toxicity which can produce headache, drowsiness, and hallucinations.

Since flucytosine is commonly combined with amphotericin-B, the renal impairment caused by amphotericin-B may increase the flucytosine levels in the body and thus potentiate its toxicity. The need to adjust the dose carefully for renal dysfunction and difficulty with quickly obtaining serum levels makes use of the agent challenging.


Amphotericin-B (AmB) and nystatin are rarities in that they are fungicidal - they kill the fungus by rupturing its cell wall. Almost all other antifungal drugs are fungistatic that act by interfering with fungal growth.

Amphotericin-B has been the mainstay of systemic Candidiasis treatment for the last several decades, and still demonstrates the broadest range of effectiveness of available drugs. AmB and nystatin are not absorbed from the GI tract. Consequently, AmB delivered by IV has been the standard treatment. While marked resistance to amphotericin-B is uncommon, many isolates of C. glabrata and C. krusei show less sensitivity to amphotericin-B and maximal doses are recommended.

AmB is highly toxic to the liver (Amphotericin-B is the most highly toxic antimicrobial in clinical use today), and so AmB IV treatments must be monitored carefully. Variants of AmB called lipid formulations are now available that are much less toxic -- all must be delivered by IV.

AmB is commonly administered in combination with another drug, especially flucytosine since they appear to be synergistic, but also in conjunction with the azoles.

Nystatin also demonstrates high toxicity if administered systemically, and there is no nystatin systemic preparation available at this time (a safer lipid formulation is in development); consequently nystatin is only available for topical and GI tract applications. Like AmB, nystatin can be taken safely by the oral route since it is not absorbed into the system. Nystatin is available under the brand names Mycostatin or Nilstat as a tablet (500,000 IU's), a suspension for oral rinse (5 mL dosage at 100,000 IU's per mL), and as a lozenge (also called a pastille, 200,000 units, to be taken two at a time).

There is yet no validated standard dose of oral amphotericin-B. It has so far been administered as 500 mg capsules four times a day, in suspension form as 500 mg every six hours, or as solution of 100 mg/ml, dosed at 1 to 5 ml four times daily, taken as "swish and swallow."

AmB had been commercially available in a non-absorbable form called Fungizone for GI tract treatment (especially oropharyngeal Candidiasis -- thrush of the mouth and throat), but those products have been discontinued by the manufacturer. They are, however, available from compounding pharmacies that will make up solutions or capsules from bulk powder -- these pharmacies can also provide nystatin in oral solution or in bulk powder form (nystatin is currently available in tablet form). See our page on SCORING SPECIAL Rx DRUGS for more information about compounding pharmacies.

Candida overgrowth needs to be treated both systemically and via the GI tract. AmB and nystatin in their non-absorbable form are potent drugs for intestinal Candidiasis. See the our associated page on Treatment Plan and our page on the Triple Rx Treatment Strategy for a discussion.


Caspofungin, available in IV format, is in a new class of antifungals. Caspofungin is licensed for treatment of patients with invasive Aspergillosis who are failing other therapies (amphotericin-B and/or voriconazole). It has also been used in combination with amphotericin-B and the azoles for treatment of Aspergillosis. It is fungistatic against Aspergillus, demonstrating inhibition of growing hyphal ends.

Recent data demonstrate that caspofungin is equivalent to or superior to amphotericin-B for treatment of invasive infections due to Candida. Caspofungin has excellent activity (fungicidal) against Candida. It has no activity against Cryptococcus, and has little activity against moulds other than Aspergillus. The advent of the glucan synthesis inhibitors (caspofungin and others in development) may provide the biggest advance yet in therapy of invasive candidiasis. The broad anti-Candida activity of these agents, combined with their low toxicity, promises to make them very attractive agents. However, although caspofungin has activity against Candida, it is not yet licensed for this indication. Limited safety data exist for caspofungin and the risk/benefit ratio for its use in this application would need to be carefully evaluated. However, early studies seem to indicate it will be an effective alternative for severe mucosal infections and systemic infections due to Candida, especially those due to non-albicans Candida species.

Minimal side effects have been observed.


Terbinafine, available in oral form, has primary indication in dermatological infections. It is highly lipophilic in nature and tends to accumulate in skin, nails, and fatty tissues. Terbinafine, in combination with fluconazole and itraconazole, may also yield enhanced activity against some azole-resistant Candida albicans strains.

The typical dose of terbinafine is 250 mg/day.

Adverse reactions to terbinafine are in general transient and mild. The incidence of these reactions has been found to be about 10%, mostly involving the gastrointestinal system and the skin.


The following table lists typical resistance patterns of selected Candida species. In individual cases, any given species may become resistant to any agent.


-----------------Azoles -----------------


Fluconazol e

Itraconazol e



C. albicans






C. tropicalis






C. parapsilosis






C. glabrata






C. krusei



S-DD to R



C. lusitaniae







  • S = Susceptible to usual doses of this agent
  • S-DD = Susceptibility depends on the dose (fluconazole) or delivery (itraconazole) of the drug. Maximal tolerated doses must be used and blood levels may need to be checked.
  • I = Indeterminate or Intermediate. This category reflects a general lack of certainty about the testing methodology.
  • R = Resistant to usual doses of this agent



Infections due to C. krusei necessitate the use of amphotericin-B at high dosages because this organism is intrinsically resistant to fluconazole and less susceptible to itraconazole, ketoconazole, and amphotericin-B.

Infections due to C. lusitaniae or C. guilliermondi necessitate the use of fluconazole because these isolates frequently are intrinsically resistant to amphotericin-B or develop resistance to amphotericin-B while the patient is on therapy.


Fluconazole is the drug of choice for treating thrush. Alternatives include itraconazole, ketoconazole, clotrimazole troche, nystatin oral suspension or powder dissolved in the mouth, AmB oral suspension, and, in extreme cases such as AIDS patients, AmB IV or caspofungin IV. (Caspofungin has demonstrated activity against thrush, but is not licensed for this application and limited safety data exists.)

Candidiasis of the mouth can be treated topically since the antifungal can be held in the mouth for an extended period of time, giving ample exposure of the yeast to the drug; However, Candida esophagitis requires systemic therapy, usually with fluconazole or itraconazole for at least 14-21 days. Itraconazole alone, as well as itraconazole and flucytosine combination, proved to have good long term therapeutic efficacy in esophageal candidiasis in AIDS patients.

Oral thrush may be treated with either topical (swish and swallow) antifungal agents (nystatin, clotrimazole, amphotericin-B oral suspension) or systemic oral azoles (fluconazole, itraconazole, ketoconazole). In patients who are positive for HIV, the infections tend to be slower to respond, and approximately 60% of patients experience a recurrence within 6 months of the initial episode. Approximately 3-5% of patients with advanced HIV may not respond and require higher dosages in addition to immune system therapy.


Main results: Eight trials involving 418 patients satisfied the inclusion criteria and were included in this review. Only two agents, each in single trials, were found to be effective for eradicating oral candidiasis. Ketoconazole was more beneficial than placebo in eradicating oral candidiasis (RR=0.35 95% CI 0.20 to 0.61) and clotrimazole at a higher dose of 50 mg was more effective than a lower 10 mg dose in eradicating oral candidiasis, when assessed mycologically (RR=0.47 95% CI 0.25 to 0.89). Another trial demonstrated no statistically significant difference between a 10 mg dose of clotrimazole, and placebo.

The study indicates that there is no evidence among the trials that were reviewed indicating that either fluconazole or itraconazole were effective in treating oral Candidiasis.

Reviewers' conclusions: There is evidence that ketoconazole may eradicate oral candidiasis and that a higher dose of clotrimazole may give greater benefit than a lower 10 mg dose. Because of the small number of trials formatted so that consistent data could be extracted, the evidence is weak and unreliable. Cochrane Library 2003, issue 1.


Sunnybrook Health Center, Ontario, Canada

CTCL (Center for T-Cell Lymphoma), offers PDR pages
     a sample page is here.



Cochrane Library

U. of Iowa, Dept. of Medicine & Pharmacology, Dr. D.J. Diekema

University of Utah, School of Medicine

University of Leeds, School of Biochemistry and Microbiology, London, UK

Fungal Research Trust