Yellow, thick toenails? Yeast infection? UTI? 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,, a clinical associate professor at the University of Washington School of Pharmacy in Seattle.
Even though superficial 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 skin 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 Food and Drug Administration (FDA) generally believes these treatments are effective, they have few side effects and can be used safely without a doctor’s supervision.
Thanks to advertising, the most famous fungal infection is onychomycosis, or nail fungus, which occurs more commonly in toenails than fingernails according to Paul Lyons, MD, senior associate dean of 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.
“Toenail 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.
Jain agrees. “There can be times when you use oral therapies in infections because they don’t respond to topical therapy,” she 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.”
Diflucan, Jublia, Nizoral, Extina, Mycelex and Monistat 7
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 for pregnant women who use Diflucan (fluconazole). It’s sometimes used to treat toenail fungus, although it is not approved for this, but the FDA’s concern is its approved use for vaginal yeast infections in pregnant women. While the FDA considers the standard single dose of 150 mg of fluconazole to be safe in pregnancy, the evidence suggests that taking doses greater than 150 mg (400 mg to 800 mg per day) or taking fluconazole for extended periods of time may harm an unborn baby.
The FDA’s concern was based on a 2016 study in which women who used the oral version of fluconazole had a slightly higher risk of miscarriage than those who used the topical version. The study from Denmark found reports of abnormalities in babies at birth whose mothers took as few as one to two doses of oral fluconazole at 150 mg. Previously, abnormalities had only been seen at higher doses (400 mg to 800 mg) for longer periods of time. The FDA also advised “caution in prescribing oral fluconazole during pregnancy.”
Although the increased risk was only slightly higher, a February 2019 study also shows a link between oral fluconazole and miscarriage. Researchers looked at the medical records of 320,000 pregnant women in Quebec. Women who took oral fluconazole had a miscarriage rate of 12% compared to 6% for women who never took the drug, according to findings published in the Canadian Medical Association Journal. Women who took fluconazole had an increased miscarriage risk whether they took the standard single 150 mg dose or more than 150 mg.
In a commentary to the study, Drs. Vanessa Paquette and Chelsea Elwood, both of the British Columbia Women’s Hospital and Health Centre, wrote: “The study re-emphasizes safe prescribing practices in pregnancy, which include confirming the correct diagnosis and then choosing the safest medication with the largest body of data in pregnancy at the lowest appropriate doses.”
In 2018, Diflucan’s prescribing information was modified to include all the available information on the use of fluconazole in pregnant women. In an October 2019 statement, the FDA declared that there is no conclusive evidence that a single 150 mg dose of oral fluconazole increases the risk of miscarriage or stillbirth. However, the Centers for Disease Control and Prevention (CDC) recommends that pregnant women use only antifungal creams, not oral meds, during pregnancy for yeast infections. But the question as to how doctors should treat women with systemic fungal infection during pregnancy still remains.
Azole antifungals also raise liver enzymes — a potential warning sign of liver damage. In worst-case scenarios, they may even cause liver failure. In a study published in the World Journal of Hepatology, researchers reviewed over 68,000 reports of liver injury and found that a disproportionate number of these were related to the use of systemic antifungal drugs, including nearly all the azoles. And in 2016 the FDA warned healthcare professionals against the use of Nizoral (ketoconazole) pills for skin and nail fungal infections due to the risk of serious liver damage, among other problems. The agency declared that ketoconazole pills should only be used to treat serious fungal infections if no other antifungal drug is available, and it should not be used for skin and nail infections, which are not life-threatening and not approved uses of the drug.
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. The combination can increase the risk of muscle pain and weakness that sometimes accompanies statin use. Azoles also need to be used with caution if you’re using warfarin (Coumadin) or other anticoagulants like it because they increase the drugs’ anticoagulant activity.
Lamisil (terbinafine) has fewer interactions with other drugs, but caution is needed if it’s combined with certain antidepressants, beta-blockers, antiarrhythmics and other heart drugs. Your doctor may need to adjust dosages. Common side effects of terbinafine include headaches, diarrhea, dyspepsia (heartburn, nausea) and skin rash.
Gris-PEG (griseofulvin) is commonly prescribed for skin infections like ringworm, and is also approved for toenail fungus. Gris-PEG can interact with anticoagulants, such as warfarin, and barbiturates, such as phenobarbital. Your doctor may need to adjust your dosage of either drug. Gris-PEG may also cause the failure of low-dose contraceptive pills in some women.
Perhaps the most dangerous antifungal medication is Fungizone (amphotericin B), an intravenously delivered antifungal medication used to treat serious fungal infections in hospital settings. First approved in the late 1950s, kidney failure and permanent kidney damage were among the medication’s most serious side effects. In the 1990s researchers developed new technologies to improve the drug’s delivery and reduce risks of side effects. However, despite these advances, the use of amphotericin B still carries kidney and other risks and is limited to the treatment of people with progressive and potentially life-threatening fungal infections.
“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.
As for safety concerns and managing side effects, Jain notes that medical teams keep a close eye on patients who require prescription antifungals.
When Antifungals Develop 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.
Antifungal resistance can develop if a fungal infection is not treated long enough or if the dosage of the antifungal drug is too low. 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 also contribute to resistance.
The use of antibiotics plays a role in antifungal resistance, possibly because antibiotics reduce protective as well as harmful bacteria in the gut, leaving the system more vulnerable to fungal infection. In a study in the journal Antimicrobial Agents and Chemotherapy, researchers collected blood samples from 444 hospitalized patients who had developed fluconazole resistant candidemia, a blood infection caused by the fungus Candida. About 92% of the patients had received treatment with one or more antibiotics within 30 days before the onset of candidemia, suggesting the fungal infection was associated with antibiotic exposure. The researchers suggested reduction of bacteria in the gut may have allowed for fungal infection with resistant Candida.
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.
In a review in the journal Science experts note that resistance to antifungal drugs is worldwide, due in part to the multiple uses of these drugs. For example, azoles are used in human and animal health as well as crop and wood protection. Another common use of antifungals, one that many of us wouldn’t even think of, is in what’s known as antifouling coatings. These are paints applied to the hull of a boat to prevent aquatic organisms from attaching and multiplying. These coatings can contain substances that destroy fungi, bacteria and other organisms harmful to boats. The Science article calls for the development of antifungal chemicals with new modes of action and new disease strategies to avoid overreliance on fungicides “to counter the escalating risks of fungal disease.”
Do Home Remedies Work?
Perhaps you’d prefer to try home remedies? According to the National Center for Complementary and Integrative Health (NCCIH), some research shows that applied to the skin, bitter orange oil may help with athlete’s foot, jock itch and ringworm infections. There is also some evidence that tea tree oil may be helpful for athlete’s foot or nail fungus, according to the NCCIH.
There is limited evidence that apple cider vinegar can help treat vaginal yeast infections and thrush, a fungal infection in the mouth. When used on the skin, apple cider vinegar should be used with caution because it can lead to a chemical burn due to its acid content.
Garlic has shown anti fungal properties against a yeast in the Candida family, as well as fungal infections of the scalp. And an early study showed that a cream containing a component of garlic relieved athlete’s foot in all 34 study participants. Some research has shown that garlic is active against toenail fungus. However applying garlic directly to the skin can result in burns and blistering, so do it with caution if you decide to try it.
Laboratory experiments have shown possible benefits of baking soda for toenail fungus, and mouthwash and essential oil mixtures containing lavender for Candida infections. Success in a lab experiment does not necessarily translate to successful treatment in a person, but these may be safe alternatives to medication. If you decide to try one of these, be sure to talk to your doctor if your home remedy isn’t working.
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, particularly 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.
However you can take precautions to help protect yourself from developing common fungal infections of the feet and skin, or having an infection recur. Following are some suggestions from the American Osteopathic College of Dermatology (AOCD):
- Keep your feet clean, cool and dry, change socks regularly, and wear shoes that “breathe” like leather rather than plastic. Make sure your shoes fit correctly and are not too tight.
- Discard old shoes, boots, slippers and sneakers. Don’t share footwear with others.
- Avoid walking barefoot in bathrooms, locker rooms, gyms, on carpeting and in public bathing areas. Wear slippers or stand on a towel.
- Keep your toenails short, cut straight across and avoid ingrown toenails. Don’t use the same clippers on infected nails and healthy nails.
- Make sure family members and people you have close contact with treat any fungus infections they may have to avoid trading back and forth.
- Applying an antifungal powder to shoes every day can help keep fungus from growing.
To help deal with a fungal infection or prevent one from recurring, the AOCD suggests the following:
- Use prescribed medication completely and as directed. The fungus may still be present long after a rash is no longer visible.
- To help prevent early regrowth of the fungus, apply an antifungal cream to the bottom of your feet and on your nails about twice a week.
- For a body fungus, in the groin or elsewhere on the skin, try using a dandruff shampoo on the area twice a month. Lather it up and leave it on the skin for about five minutes, then wash it off completely.
The National Institute of Allergy and Infectious Diseases (NIAID) is supporting research to find better ways of diagnosing, preventing, treating and even developing vaccines for fungal infections. An important goal is to zero in on the causes of increasing resistance to antifungal medicines, and develop new treatments to target drug resistant fungi.
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