Fungal infections range from minor skin irritations to life-threatening infections of the blood and tissues. There are a variety of types of antifungal drugs and treatments available in topical, oral, ophthalmic, and parenteral (injectable) dosage forms. Antifungal agents are sometimes referred to as antimycotic agents. Like bacteria, the term “fungi” refers to a broad range of infectious organisms. Fungi are not the same as bacteria or viruses and therefore are not treatable with antibiotics or antivirals.
Most healthy immune systems are more than capable of staving off serious fungal infections, however, there are fungal infections with a mortality rate similar to malaria or tuberculosis. Current antifungal medications are prone to side effects and resistance. Here we will discuss the different types of antifungals, the way they work, and their side effects and safety profiles.
There are many more antifungals than listed above.
Antifungals are agents that inactivate or kill fungi. There are a broad spectrum of fungi that cause infections including Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus. The most common cause of infections is C. albicans. It is a naturally occurring fungi in the human mucosa, but when given the chance, candida infections can become life-threatening infections. There are four classes of antifungals currently in use clinically: polyenes, pyrimidines, azoles, and echinocandins. Each class works in a unique way to fight fungal infections.
In a general sense, antifungals inhibit the growth of fungi by destroying the fungal cell structure. Each class of antifungals has a unique mechanism of action to achieve this goal. Without an intact and healthy cell, the fungal cell can no longer survive or proliferate.
Aspergillosis
Blastomycosis
Candida urinary tract infection (UTI)
Candidemia
Chromomycosis
Chronic mucocutaneous candidiasis
Cryptococcal meningitis
Cryptococcosis
Dermatophytosis
Esophageal candidiasis
Eumycetoma
Febrile neutropenia
Fungal endocarditis
Fungal meningitis
Fungal peritonitis
Fusariosis
Histoplasmosis
Mucormycosis
Ocular fungal infection
Onychomycosis (fingernail and toenail)
Paracoccidioidomycosis
Pseudallescheriasis
Sporotrichosis
Systemic candidiasis
Tinea barbae
Tinea capitis
Tinea cruris (jock itch)
Tinea pedis (athlete’s foot)
And many others
Azole antifungals are named for the chemical structure known as an azole ring that comprise the structure of the medication class. There are two sub-groups within this class: those with two nitrogens in the azole ring imidazoles, and those with three nitrogens (triazoles). The azole class provides a broad spectrum of coverage for a variety of types of fungal infections. The azoles work by inhibiting a specific cytochrome P450 called lanosterol 14-alpha-demethylase. This blocks the formation of ergosterol, one of the main components of the cell membrane of the fungus. This causes significant damage to the cell membrane leading to the death of the fungal cell.
Examples of imidazoles: clotrimazole, econazole, ketoconazole, miconazole, and tioconazole
Examples of triazoles: fluconazole, itraconazole, posaconazole, and voriconazole
Echinocandins are lipopeptide molecules that target the cell wall in their mechanism to inhibit growth of the fungal cells. They work by inhibiting the enzyme responsible for the synthesis of glucan, the major component of the fungal cell wall. This leads to cell wall damage. This mechanism makes them very effective in the treatment of serious and invasive fungal infections such as candidiasis infections of the blood.
Examples of echinocandins: micafungin, anidulafungin, and caspofungin
Polyene antifungals bind to the main sterol of the fungal cell membrane, ergosterol. Rather than blocking the synthesis of ergosterol like the azole antifungals, polyenes latch onto the existing ergosterol and depolarize the membrane. This leads to cell death. Polyenes are not absorbed into the bloodstream when given orally, but they are highly effective against fungal infections of the gastrointestinal tract, such as oral thrush. When treating systemic fungal infections, a polyene antifungal must be given via direct injection to the bloodstream.
Examples of polyenes: amphotericin b, nystatin
Pyrimidines are unique because they are the only class of antifungals that work on the inside of the cell. Pyrimidines are not used as single therapy against fungal infections, rather as part of a multi-drug regimen. This class of drugs works by causing a faulty miscoding of the RNA of the cell when then inhibits DNA synthesis within the cell.
Examples of pyrimidines: flucytosine
There are other antifungals who do not fit one of the four primary classifications. These include griseofulvin and terbinafine.
Adult men and women can take or use antifungals. Those with liver disease or impaired hepatic function may need to have their doses of antifungals adjusted appropriately to avoid toxicity.
Seniors can take or use antifungals medications but may be at a more increased risk for decreased hepatic function which should be recognized prior to initiating any antifungal therapy.
Not all antifungals can be used safely in children. Your child’s healthcare provider will review your child’s specific condition to determine which options are most appropriate.
Your obstetrician will provide specific guidance on each antifungal therapy available. In general, systemic antifungals should be avoided during the first trimester, and if at all possible, throughout the entire pregnancy. The use of antifungals in pregnancy has been linked to birth defects, heart defects, and spontaneous abortions.
Systemic use of antifungals while breastfeeding may be safe. Your healthcare professionals, including your pharmacist, can provide specific information on the antifungal you are prescribed.
Topical use, such as creams or powders, are generally considered safe.
No active recalls found at this time.
Do not use antifungals if you have had a hypersensitivity reaction to the specific class of antifungals of which you are being prescribed.
If you have a medical condition that causes QT prolongation or other rhythmic disorders of the heart, or if you have a family history of these disorders or take medications that may cause them, you may not be able to take certain antifungal drugs.
Patients with liver or kidney disease may not be able to take certain antifungals or may need their dosages adjusted to account for their renal or hepatic impairment if antifungals are absolutely necessary.
Your doctor may want to check your electrolyte levels and cardiac function prior to initiating antifungal therapy. If you have had recent cardiac issues, you may not be a candidate for antifungal therapy.
Ongoing treatment with antifungals may require frequent blood work to ensure the continued health and function of your liver, kidneys, and heart.
Antifungals have the potential to cause a significant amount of drug interactions. Make sure your healthcare provider is aware of all of the medications you are taking prior to starting antifungal treatment.
No, antifungals are not controlled substances.
The potential for and severity of side effects can vary based on the type of antifungal being used. Topical antifungal application, such as creams, powders, and sprays used for fungal skin infections have limited adverse effects which may include:
Irritation
Burning
Stinging
Pruritus (itching)
Erythema
Maceration
Contact dermatitis
Pelvic pain and cramps (when used for vaginal yeast infections)
Systemic use of antifungals for fungal infectious diseases has the potential for more troublesome and serious adverse events. The most common may include:
Nausea
Dizziness
Abdominal pain
Diarrhea
Headache
Lethargy
Nervousness
Somnolence
Rash
Elevated liver enzymes (AST or LST)
Gynecomastia
More serious adverse reactions to the systemic use of antifungals may include:
Hepatic failure
Hepatotoxicity
Adrenal insufficiency
Hypersensitivity reaction
Anaphylaxis
Thrombocytopenia
Leukopenia
Hemolytic anemia
The cost of your antifungal medication will vary greatly depending on the medication used, the route of administration, and your insurance coverage. Generally, over-the-counter topical antifungals are very cost-effective. For example, generic topical clotrimazole 1% cream, used frequently for athlete’s foot, ringworm, or jock itch, may cost less than $10. The prescription-only topical antifungals will cost you more. For example, ketoconazole 2% cream in a 50G tube can cost more than $600 with no prescription medication coverage. SingleCare offers savings on most prescription drugs and can bring this price down to $115 with their free prescription coupons and cards.
Your insurance may have formulary restrictions which will suggest that you try regimens of certain preferred drugs first before they will approve the use of more expensive medications to treat your fungal infection. Before filling your antifungal medication, always check with SingleCare to make sure you are paying the lowest price.
Kristi C. Torres, Pharm.D., is a 2005 graduate of The University of Texas at Austin. Her professional background includes academic teaching roles, district-level management for a nationwide pharmacy chain, and clinic-based pharmacy management. Dr. Torres has a wide range of experience in pharmacy operations and has traveled to many states to open and convert clinic-based pharmacies for one of the largest healthcare systems in the nation.
Currently, she works for Tarrytown Expocare Pharmacy in Austin, Texas, serving the intellectual and developmental disability community. There, she leads the order entry team, overseeing orders from across the country.
Dr. Torres began working in pharmacy at the age of 16 in a small East Texas town. She currently resides in Round Rock, Texas, with her daughter and a Shih-Tzu puppy.
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