Antifungal Medicines: Fighting Infections but Becoming Resistant

Yellow, thick toenails? Yeast infection? How antifungal treatments stack up, some surprising side effects, and tips for prevention

Bacterial and viral infections seem to make the daily news, but ever wonder why fungal infections — and the consequences of their treatment — rarely make headlines?

“Fungal infections can be bothersome, but they are generally low acuity and not life-threatening in people with healthy immune systems,” says Rupali Jain, PharmD, BCPS, AAHIVP, a clinical associate professor at the University of Washington in Seattle School of Pharmacy.

Even though fungal infections affecting the outer layer of skin and other bodily surfaces are rarely serious, they can look ugly (toenail fungus), can be irritating (vaginal itching), and are relatively common, accounting for 25% of all fungal infections. In addition to toenail and vaginal yeast infection (which is caused by a fungus), common infections include ringworm, athlete’s foot, scalp infection and jock itch.

They are typically treated with the same family of antifungals. You can often treat less-persistent and less-serious infections with over-the-counter antifungal creams, powders and gels. The FDA (Food and Drug Administration) generally believes these treatments have low risk for side effects and therefore do not require a doctor’s supervision to use them safely.

Thanks to advertising, the most famous fungal infection is onychomycosis, or nail fungus. According to Paul Lyons, MD, senior associate dean of Medical Education at the University of California Riverside School of Medicine, the condition is not all that common despite seemingly constant TV and web ads for nail fungus-fighting medications.

“Nail fungus is actually inside the toenail itself, so generally it’s not effectively treated with anything you’d apply to the nail’s surface,” Lyons says. Over-the-counter medications cannot fight a fungus under the nail or in the bloodstream.

“You have to take an oral medication, which gives you a higher and more significant exposure to the medication,” Lyons explains. This increases the risk for side effects.

About Azoles

One class of antifungals commonly used to treat fungal infections is called azoles, with brand names such as Diflucan, Jublia, Nizoral, Extina, Mycelex and Monistat 7. Over-the-counter azoles (creams, lotions, powders, etc.) may cause some burning or irritation to the area where they are applied, but these side effects are rare. Prescription azoles have more-serious side effects.

In 2016, the FDA released a statement announcing the agency was re-evaluating the safety of one prescription azole, Diflucan (fluconazole). It is often used to treat toe fungus, but the FDA’s concern is its approved use for vaginal yeast infections in pregnant women. While the FDA considers the standard single and two-time doses of fluconazole of 150 mg to be safe, the evidence suggests that taking doses greater than 150 mg (400-800 mg per day) or taking fluconazole for extended periods of time may harm an unborn baby.

Azole antifungals also raise liver enzymes — a potential warning sign of liver damage. In worst-case scenarios, they may even cause liver failure. However, Lyons says the risk for liver failure is extremely rare because medical professionals closely monitor patients taking oral azole antifungals.

Don’t use an azole if you are using the statins lovastatin, simvastatin or atorvastatin. Azoles are also contraindicated if you’re using warfarin, because they increase warfarin’s anticoagulant activity.

Lamisil is terbinafine hydrochloride. It has fewer interactions with other drugs, but headaches are a common side effect. It can also cause diarrhea, dyspepsia (heartburn, nausea) and skin rash.

Gris-PEG (griseofulvin) is more commonly prescribed for skin infections like ringworm, but can be used for toenail fungus. Gris-PEG can affect warfarin’s strength, so talk to your doctor about adjusting the dose of warfarin. Gris-PEG has also been known to cause the failure of low-dose contraceptive pills. It is contraindicated for those on phenobarbital.

Perhaps the most dangerous antifungal medication is amphotericin B, an intravenously delivered antifungal medication used to treat serious fungal infections in hospital settings. First approved in the early 1990s, kidney failure and kidney damage were among the medication’s most serious side effects. Since that time, researchers have developed new technologies to improve the drug’s delivery and reduce risks of side effects. However, despite these advances, experts agree that amphotericin B is often a last resort to treat fungal infections these days.

“We rarely use amphotericin B in acute settings anymore — partly because of its side effects, and partly because we now have newer medications, including azoles, that work well systemically even for relatively serious infections,” says Lyons.

When Antifungals Develops Resistance

If you must take an antifungal medication of any kind, following your doctor’s orders is important not only in treating the fungus but in helping to prevent antifungal resistance — a problem that could make it more difficult for your body to fight off fungal infections because the fungi stop responding to the medications prescribed.

Fungi are smart, and find crafty ways to work around the medications that would otherwise kill them or keep them from growing and spreading. The overuse and unnecessary use of antifungals contribute to resistance.

Many people are familiar with the concept that eating produce and animal products treated with pesticides can increase antibiotic resistance. Fungicides are also used in farming, which is causing antifungals to become less effective — or helping fungi to become more resistant.

Newer evidence suggests that treating fungal infections for shorter time periods can be as effective as using them for longer times. Exposing fungi to medicine for less time gives them a smaller window of opportunity to find adaptations to circumvent medicines.
As for safety concerns and managing side effects, Jain notes that medical teams keep a close eye on patients who require prescription antifungals.

“There can be times when you use oral therapies in infections because they don’t respond to topical therapy,” Jain says. “Systemic (i.e., IV or oral) therapy is generally safe, but in rare circumstances, these medications can cause liver damage if precautions are not taken such as monitoring lab tests and side effects.”

Do Home Remedies Work?

Perhaps you’d prefer to try home remedies? Most are not proven to work, but for a mild toenail fungus Reader’s Digest suggests tea tree oil, baking soda, cornmeal, white vinegar or apple cider vinegar, mouthwash, lavender oil or garlic.


When it comes to staying safe, education is, perhaps, one of the most important keys to avoiding and reducing risk for developing an infection, as certain conditions can increase your risk for infections. People who have serious long-term illnesses such as cancer, HIV or AIDS, or who are hospitalized in intensive care units, are more susceptible to certain fungal infections than healthy people.

Some commonly used medications, such as corticosteroids, which are used to treat many conditions, including arthritis, inflammation, asthma, emphysema, autoimmune disorders and psoriasis, can weaken the immune system over time and put you at risk for developing fungal infections, too.

Frieda Wiley

Frieda Wiley

Frieda Wiley is a medical writer and consultant pharmacist who calls the serene Piney Woods of East Texas home. Her work has appeared in Arthritis Today, Diabetes Self-Management, Everyday Health, and Next Avenue. She also develops content for medical students and allied healthcare professionals.

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