Nov, 14 2025
When you take an antifungal for a stubborn nail infection or a systemic fungal illness, you’re not just fighting fungus-you’re putting your liver on the line. Many people assume these drugs are safe because they’re prescribed by doctors, but the truth is, some antifungals carry serious, sometimes deadly, risks to the liver. And those risks don’t always show up in blood tests until it’s too late.
Not All Antifungals Are Created Equal
There are four main classes of antifungals used today: azoles, polyenes, echinocandins, and allylamines. Each works differently, and each has a different risk profile for your liver.Among the azoles-fluconazole, itraconazole, voriconazole, posaconazole, and ketoconazole-ketoconazole is the most dangerous. It’s so risky that the FDA restricted its use in 2013 and the European Medicines Agency pulled it off the market entirely in 2013. A UK study found that about 1 in 500 people taking ketoconazole developed serious liver injury. Some patients saw their liver enzymes spike over 1,200 U/L (normal is 7-56). One Reddit user described being hospitalized after just three weeks on the drug. Today, ketoconazole is only used as a last resort for rare fungal infections when nothing else works.
Voriconazole and itraconazole aren’t far behind. Data from the FDA’s adverse event database shows they cause more reported cases of liver injury than fluconazole. Voriconazole, often used in cancer patients with invasive fungal infections, can damage the liver within 2 to 8 weeks of starting treatment. A 2022 study found that people with a specific gene variation (CYP2C19) are nearly four times more likely to develop liver problems on voriconazole. That’s why some hospitals now test for this gene before prescribing it.
Fluconazole is the safest of the azoles, but it’s not risk-free. If you’re on it for more than two weeks-or if you’re older, have existing liver disease, or take other medications that affect the liver-your doctor should monitor your liver enzymes. Many primary care providers skip this step, especially when prescribing it for nail fungus. That’s a mistake.
Terbinafine, an allylamine used mostly for fungal nails and skin, has the lowest overall risk-only about 0.1% of users develop liver injury. But here’s the catch: it still carries a black box warning from the FDA. That’s the strongest warning they give. Liver damage from terbinafine often shows up after 4 to 6 weeks of treatment. One Healthline user reported jaundice and fatigue at week five. Symptoms can be subtle: tiredness, nausea, dark urine. By the time you feel sick, your liver may already be damaged.
Echinocandins-caspofungin, micafungin, and anidulafungin-are newer drugs used in hospitals for serious bloodstream infections. For years, doctors thought they were liver-safe. But a 2022 real-world analysis flipped that idea. Anidulafungin had the highest death rate among antifungals linked to liver injury-50%. That sounds terrifying, but it’s likely because these drugs are given to the sickest patients: those already in intensive care, with failing livers, or on multiple other toxic drugs. Micafungin, by contrast, shows the cleanest safety record among echinocandins.
How Your Liver Reacts to Antifungals
Your liver breaks down these drugs using enzymes, especially the CYP450 family. That’s where the trouble starts. Many antifungals block or overstimulate these enzymes, which doesn’t just affect the antifungal itself-it affects everything else you’re taking.For example, voriconazole can raise levels of blood thinners like warfarin, leading to dangerous bleeding. Itraconazole can spike levels of statins, increasing the risk of muscle damage. Even common over-the-counter drugs like ibuprofen or acetaminophen can become more toxic when mixed with certain antifungals.
Some antifungals also interact with grapefruit juice, which blocks the same liver enzymes. One patient on itraconazole drank grapefruit juice daily and ended up in the ER with liver failure. That’s not a myth-it’s documented in case reports.
Alcohol is another red flag. Combining any antifungal with alcohol increases liver stress. It’s not just about drinking heavily-even one drink a day can tip the balance in someone already at risk.
Who’s Most at Risk?
Age matters. People over 65 are nearly eight times more likely to develop antifungal-induced liver injury than younger adults. Why? Their livers process drugs slower. They’re also more likely to be on multiple medications, which adds up.People with preexisting liver disease-like fatty liver, hepatitis, or cirrhosis-should avoid ketoconazole and use other antifungals with extreme caution. Even healthy people aren’t immune. A 2020 study found that 1 in 3 patients taking terbinafine for nail fungus never had their liver tested. That’s a huge gap in care.
Genetics play a bigger role than most realize. If you’re a poor metabolizer of CYP2C19, you’re at higher risk for voriconazole toxicity. That’s not something your doctor can guess without a simple blood test. Some hospitals now screen for this before prescribing.
What Monitoring Should You Expect?
Good care means regular blood tests. The Infectious Diseases Society of America says all systemic antifungals need a baseline liver test before starting. After that:- Ketoconazole, itraconazole, voriconazole: Weekly blood tests for the first month, then every two weeks.
- Fluconazole: Only if you’re on it longer than two weeks or have risk factors.
- Terbinafine: Test at 4-6 weeks, then every few weeks if treatment lasts longer than 8 weeks.
Your doctor should check ALT and AST levels-the main liver enzymes. If they rise above 3 times the upper limit of normal and you have symptoms like nausea or pain under your right ribs, stop the drug. If they hit 5 times the limit-even without symptoms-stop it.
But here’s the problem: most primary care doctors don’t know this. A 2020 study found only 37% of providers ordered proper liver monitoring for terbinafine. If you’re prescribed an antifungal for a fungal nail infection, don’t assume your doctor will check your liver. Ask. Push for it.
What to Do If You’re Already on an Antifungal
If you’re currently taking one of these drugs, here’s what to do:- Check your last liver test date. If it’s been more than a month on a high-risk drug, call your doctor.
- Write down every other medication and supplement. Include vitamins, herbal products, and OTC painkillers. Bring it to your appointment.
- Watch for symptoms. Fatigue, nausea, loss of appetite, yellowing eyes or skin, dark urine, or pain under your right ribs aren’t normal. Don’t wait for a blood test-call your doctor immediately if you notice any.
- Don’t drink alcohol. Even one drink can increase your risk.
- Don’t stop the drug on your own. If you suspect liver trouble, contact your doctor before quitting. Some infections need to be managed carefully.
The Future Is Safer-But Not Yet
The good news? The field is changing. New antifungals like olorofim and ibrexafungerp are being designed with liver safety as a top priority. Early trials show they cause 78% fewer liver enzyme spikes than older azoles. The FDA is also using AI to scan adverse event reports faster, so dangerous patterns are caught sooner.But today, the safest antifungal is the one you don’t need. For mild skin or nail infections, topical treatments (creams, sprays, nail lacquers) are often enough. Save the oral drugs for serious cases.
And if you’re prescribed an oral antifungal-especially for something like athlete’s foot or toenail fungus-ask: Is this really necessary? Are there safer options? Can we check my liver before and during treatment?
Antifungals save lives. But they can also harm them. The difference often comes down to awareness, testing, and asking the right questions.
Can antifungals cause permanent liver damage?
Yes, in rare cases. While most liver injury from antifungals reverses after stopping the drug, some patients develop acute liver failure requiring a transplant. Ketoconazole has been linked to the most transplant cases. Early detection and stopping the drug quickly can prevent permanent damage.
Is terbinafine safe for long-term use?
Terbinafine is generally safe for short-term use (6-12 weeks), but long-term use increases liver risk. The FDA recommends liver function tests at 4-6 weeks and then periodically if treatment lasts beyond 8 weeks. Never take it for months without monitoring.
Why was ketoconazole taken off the market in Europe?
The European Medicines Agency withdrew oral ketoconazole in 2013 because of its high risk of severe liver injury, adrenal gland damage, and dangerous drug interactions. It’s now banned for all uses in Europe and restricted in the U.S. to only the most serious fungal infections when no other options exist.
Can I take antifungals if I have hepatitis C?
You can, but with extreme caution. People with hepatitis C have reduced liver function and are more vulnerable to drug-induced injury. Fluconazole or micafungin are preferred over voriconazole or itraconazole. Always inform your doctor about your hepatitis C status before starting any antifungal.
Do natural antifungals like coconut oil or oregano oil protect the liver?
No. While some natural products may help with mild skin fungus, they are not proven to treat systemic infections. Relying on them instead of prescribed antifungals can allow a serious infection to spread, which puts far more stress on your liver. Natural doesn’t mean safe-or effective-for deep fungal infections.
How do I know if my liver is being damaged by an antifungal?
You might not feel anything at first. Early signs include unexplained fatigue, nausea, loss of appetite, or dark urine. The most reliable way to detect damage is through blood tests that measure ALT, AST, and bilirubin. Don’t wait for symptoms-ask for regular liver tests if you’re on a high-risk antifungal.