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Antifungal Agents

Fungicide, Antifungals, Antifungal Drugs

About

About antifungal agents

Antifungal agents are medications used to treat fungal infections, which are among the most common skin disorders. These drugs may be given in topical (applied directly to the affected area) or systemic (spread throughout the entire body) form to treat invasions of fungi (a plant-like organism) into areas of the body, such as the toes, groin, under the breasts, scalp or nails. In some cases, antifungal agents are used to prevent fungal infections in people who are at risk, including AIDS patients, cancer patients and individuals taking immunosuppressants.

In most cases, topical antifungal agents are used to treat minor infections because they can be directly applied to the affected area and tend to have fewer side effects than systemic antifungal agents. Most fungi typically reside in the top, dead layer of skin cells, where they are vulnerable to topical agents. These drugs are available in both over-the-counter and prescription formulations. They are sometimes combined with topical steroids and/or antibacterial agents.

Typically, topical antifungal agents are applied to the infected area once or twice a day. Treatment normally continues for seven to 10 days, though patients should always follow the directions from their physician or the product's manufacturer. In some cases, topical medications may have to be applied over long periods of time before an infection is effectively treated.

Some types of topical medications (e.g., ciclopirox) take the form of a lacquer (polish) that can be painted directly onto the fingernails or toenails. This form of antifungal agent generally must be used for a year or more.

More severe forms of fungal infection – particularly of the scalp and nails – are treated with systemic antifungal agents, which may be used in combination with topical agents for several weeks. Systemic forms of the drug may also be recommended for extensive infections, infections that fail to respond to topical antifungals and infections that affect hair-bearing areas. Taken orally or intravenously, systemic agents are prescription medications that have a higher risk of side effects than topical antifungals. As a result, some physicians require that patients taking systemic antifungal agents be monitored with blood tests to ensure that liver or kidney damage has not occurred.

Patients who use antifungal agents should closely follow their physician’s recommendations about proper use. In some cases, patients stop taking their medication because the skin appears to have cleared. However, the infection may remain active and is more likely to worsen in patients who stop treatments before they are complete.

Types

Types and differences of antifungal agents

There are several different kinds of antifungal drugs that are prescribed to fight fungal skin infections. These medications can be divided into systemic antifungals (which are taken in pill form or intravenously) and topical antifungals (which are applied as creams, lotions, powders, aerosols, gels, lacquers or shampoos).

Systemic antifungals include:


Generic Name Brand Name(s)

fluconazole

Diflucan

griseofulvin*

Gris-PEG, Fulvicin P/G, Grifulvin V

itraconazole

Sporanox

ketoconazole

Nizoral

terbinafine

Lamisil

*The antifungal medication griseofulvin is rarely used today to treat infections because it is less effective and has more side effects than other drugs. However, this medication is frequently used as an alternative if a patient is allergic to another form of antifungal medication or susceptible to its side effects.

Most topical antifungals can be further subdivided into one of three major classes:


  • Polyenes. Developed in the 1950s, polyenes were the first antifungal agents. These drugs work by binding to the membranes of fungal cells and causing them to leak essential cell components through the walls. This causes the fungal cells to die.
    Generic Name Brand Name(s)

    amphotericin B

    Fungizone

    nystatin

    Mycostatin, Mytrex, Nystop

  • Azoles. These drugs were developed to treat fungal infections that did not respond to polyenes. They work by blocking production of ergosterol, a substance created by the cell wall of fungus. When the cell wall lacks sufficient amounts of ergosterol, it becomes weak and unable to support further growth. Eventually, the fungal cells die as a result of this deficiency.
    Generic Name Brand Name(s)

    clotrimazole

    Lotrimin, Mycelex

    econazole

    Spectazole

    ketoconazole

    Nizoral

    miconazole

    Monistat-Derm, Micatin

    oxiconazole

    Oxistat

    sulconazole

    Exelderm

  • Allylamines and benzylamines. Developed in the 1980s, allylamines marked an advance in both the destruction and inhibition of fungi growth. Like azoles, both allylamines and benzylamines disrupt the production of ergosterol in the cell wall of fungi, leading to the eventual death of the fungus. However, these drugs achieve this by blocking an earlier step in the ergosterol production process.
    Generic Name Brand Name(s)

    butenafine

    Mentax

    naftifine

    Naftin

    terbinafine

    Lamisil

Other topical antifungals include:


Generic Name Brand Name(s)

ciclopirox

Loprox

selenium sulfide

Selsun, Exsel

tolnaftate

Tinactin

undecylenic acid

Cruex, Desenex

Conditions

Conditions treated with antifungal medications

Antifungal agents are used to treat fungal infections, one of the most common skin disorders. Fungal skin infections most often occur in moist areas of the body, such as the toes, groin or under the breasts. They can also affect other areas, such as the scalp or nails.

The fungi either live in the top layer of the skin cells and cause minor irritation, or burrow deeper into the skin and cause symptoms such as itching (pruritus), swelling, blistering and scaling. The major types of fungal infections treated with antifungal agents include:


  • Candidiasis. Also known as a yeast infection, it is the result of yeast infecting the skin or mucous membranes. Yeast infections of the vagina or anus are often treated with medicated suppositories. Yeast infections in the mouth (thrush) are treated with medicated mouthwash or lozenges.
  • Ringworm. The more common name for the tinea infection, it is the result of infection with fungi that usually cause ring-shaped, red, scaly patches. Types of ringworm include athlete’s foot (tinea pedis), ringworm of the hands (tinea manuum), jock itch (tinea cruris), and ringworm of the scalp (tinea capitis), nail (tinea unguium) and body (tinea corporis). Ringworm of the scalp is often treated with an oral antifungal for a period of four to eight weeks. In addition, an antifungal shampoo may be recommended as an adjunct therapy. Ringworm in other areas of the body may be treated with either systemic (spread throughout the body) antifungal agents or topical (applied directly to the skin) antifungals.
  • Tinea versicolor. A fungal infection in which lighter and darker patches appear on the skin, most often on the chest and back. Either topical or oral antifungal agents can be used to treat this condition.
Side effects

Potential side effects

Patients generally should not use systemic antifungal agents if they have been diagnosed with kidney disease or liver disease, as some antifungals can cause damage to these organs in rare cases. Patients should also be honest with their physician regarding their present and past use of alcohol.

In addition, patients with a history of heart failure should not take these drugs, as some antifungal drugs have been shown to weaken heart contractions. Patients with a history of reacting to antifungal agents should also avoid these medications.

Therapy with topical antifungals typically causes very few side effects. In some cases, patients may experience the following:


  • Burning
  • Skin rash
  • Itchiness (pruritus)
  • Eczema (skin appears very dry, thickened or scaly)
  • Allergic dermatitis at application site
  • Minor pain upon application

Systemic antifungals are more likely to cause side effects than topical antifungals. These side effects may include the following:


  • Headache
  • Gastrointestinal symptoms (e.g., heartburn, diarrhea, dyspepsia, flatulence, abdominal pain, nausea)
  • Skin rash
  • Itching
  • Hives (pink or white bumps that appear on or beneath the skin)
  • Thirst
  • Dizziness or faintness
  • Visual disturbances
  • Taste disturbances

Patients experiencing any of these side effects should consult their dermatologist.

To help minimize the risk of some side effects, most systemic antifungals should be taken with food.

In more serious cases, systemic antifungals can cause damage to the liver, kidneys or heart. Decreases in white blood cell count have also been reported (particularly in patients with a weakened immune system). As a result, some antifungal treatments (e.g., itraconazole, terbinafine, fluconazole) may require patient monitoring through blood tests. When properly monitored, these treatments are considered very safe.

Patients should contact their physician immediately if any of the following symptoms develop:


  • Fever
  • Unusual bruising or bleeding
  • Sore throat
  • Soreness or irritation of the mouth
  • Urine dark in color
  • Stools pale in color
  • Extreme fatigue or weakness
  • Jaundice (yellowing of the eyes and skin)
  • Decreased interest in food
  • Seizures
  • Swelling (e.g., face, throat, tongue, lips, hands, feet)
  • Breathing and/or swallowing difficulty
Interactions

Drug or other interactions with antifungals

Patients should consult their physician before taking any additional prescriptions, over-the-counter medications, nutritional supplements or herbal medications. Of particular concern to individuals using antifungals are:


  • Antacid therapies (drugs used to treat digestive symptoms)
  • Anticoagulants (drugs that help prevent blood clots)
  • Anticonvulsants (drugs that help prevent seizures)
  • Antidepressants (drugs used to treat depression and other psychiatric conditions)
  • Antihistamines (drugs that block the effects of histamine, a chemical released during an allergic reaction)
  • Antituberculosis agents (drugs used to treat tuberculosis)
  • Beta-blockers (drugs that lower blood pressure)
  • Calcium channel blockers (drugs that reduce blood pressure and improve circulation)
  • GI motility agents (drugs that promote digestion)
  • Immunosuppressants (medications that suppress the immune system)
  • Oral contraceptives (birth control pills)
  • Oral hypoglycemic agents (drugs that reduce the amount of glucose in the blood)
  • Proton pump inhibitors (drugs that reduce stomach acid)
  • Some bronchodilators (drugs that dilate [widen] airways in the lungs)
  • Thiazide diuretics (drugs that promote loss of water from the body)
  • Nonnucleoside reverse transcriptase inhibitors (drugs that treat HIV)
How to use

Pregnancy use issues with antifungal medications

There have been few studies of antifungal agents in pregnant women. The U.S. Food and Drug Administration (FDA) has classified most systemic antifungals as belonging in category C. This means animal studies have shown a risk to animal fetuses, but the drug has not been adequately studied in humans. In general, systemic antifungal medications should be prescribed for pregnant women only if the benefit of using such drugs outweighs the potential risk to the fetus. Many antifungal medications are excreted in breast milk, and therefore should not be used by nursing mothers.

Most topical antifungals are classified by the FDA as belonging to category B. This means that either animal studies have shown no risk to an animal fetus, or human studies have shown no risk to a human fetus.


Pregnancy use issues with antifungal drugs

Children younger than 2 years of age are generally not given antifungal medications. However, children older than 2 can usually use antifungal agents safely without experiencing any side effects other than those also found in adults. A child's physician should make the determination about whether the child should use the antifungal treatment.

Questions for your doctor

Patients may wish to ask their doctors the following questions related to antifungal agents:
  1. Am I a candidate for antifungal agents?
  2. How and when should I use this drug?
  3. What should I do if I miss a dose?
  4. What side effects might I develop from using the drug?
  5. Will the antifungal medications interact with any of the other drugs I take?
  6. When can I expect to see an improvement?
  7. How long will I have to take the drug?
  8. If my condition clears quickly, can I stop taking the antifungal agents?
  9. How will I know if the drug is working?
  10. What will be the next step if the drug fails?
  11. Will I require blood tests while taking the drug?

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