Fungal infections are more common than you might think. They can range from relatively harmless skin conditions like athlete’s foot to life-threatening systemic infections that affect the whole body. When you have a fungal infection, antifungal medications are the treatment of choice. But, with so many different antifungals available, how do you know which one is right for you?
Two of the most commonly prescribed antifungal medications are fluconazole and itraconazole. Both of these drugs are in the azole class of antifungals, and they’re both available only with a prescription.
So, when it comes to fluconazole and itraconazole, which is better? That’s what we’ll explore in this article. We’ll compare the two medications in terms of:
- how well they work
- which types of fungi they treat
- side effects
- drug interactions
We’ll also touch on an increasingly important topic: antifungal resistance. The more we use antifungals, the more likely it is that fungi will develop resistance to them. That’s why it’s more important than ever to choose the right antifungal medication for your specific infection.
How fluconazole and itraconazole work
Both fluconazole and itraconazole are antifungal medications, but they work in slightly different ways and affect different types of fungi.
Fluconazole
Fluconazole works by interfering with an important enzyme called cytochrome P450 in fungi. This enzyme is necessary for making ergosterol, a key component of the fungal cell membrane. Without ergosterol, the fungal cell membrane becomes weak and leaky, ultimately killing the fungus.
Fluconazole is particularly effective against many Candida species, especially Candida albicans, which causes common yeast infections. It also works against some dermatophytes, the fungi that cause skin infections like athlete’s foot and ringworm.
In the early 1990s, researchers showed that fluconazole could prevent invasive Candida albicans infections. Fluconazole is a go-to medication for treating yeast infections, thrush, and other Candida infections.
Itraconazole
Itraconazole’s mechanism of action is similar to fluconazole’s. It also inhibits the cytochrome P450 enzyme and disrupts ergosterol synthesis. But itraconazole affects a broader range of these enzymes.
Itraconazole can treat a wider range of fungal infections than fluconazole, including Aspergillus, Blastomyces, Histoplasma, and some Candida species. This makes itraconazole useful for treating conditions like aspergillosis (a lung infection caused by Aspergillus) and certain systemic fungal infections.
How Fluconazole and Itraconazole Work
To determine which antifungal medication is best for you, it’s useful to know how each drug works in your body.
Fluconazole
- Absorption: Fluconazole is easily absorbed into the bloodstream when you take it by mouth. It’s convenient for people to take because of this.
- Distribution: Fluconazole travels widely throughout the body, including into the cerebrospinal fluid (CSF) surrounding the brain and spinal cord. This ability to penetrate the central nervous system gives fluconazole an advantage when treating certain infections.
- Metabolism: Fluconazole undergoes very little metabolism.
- Excretion: Fluconazole is mainly excreted through the kidneys. People with kidney problems may need to adjust their dosage.
- Half-life: Fluconazole has a half-life of about 50 hours, meaning it takes that long for half the drug to be eliminated from the body. This allows for convenient once-daily dosing in many cases.
Itraconazole
- Absorption: Itraconazole absorption is less predictable and depends on stomach acidity and the specific formulation of the drug. Itraconazole absorbs best when taken with food and in an acidic environment.
- Distribution: Itraconazole also distributes widely in the body, but it doesn’t penetrate the CSF as well as fluconazole does.
- Metabolism: Itraconazole is metabolized by the liver using an enzyme called CYP3A4.
- Excretion: Itraconazole is primarily eliminated from the body through bile.
- Half-life: The half-life of itraconazole is approximately 42 hours but can vary depending on the formulation and individual factors.
These differences in how each drug is absorbed, distributed, metabolized, and excreted can influence which medication is more suitable for a particular infection and patient.
How well do they work and what are they used for?
Both fluconazole and itraconazole are antifungal medications, but they have different strengths and weaknesses. They are used to treat different fungal infections.
Fluconazole
Fluconazole is commonly used for:
- Vaginal yeast infections
- Thrush (oral candidiasis)
- Esophageal candidiasis
- Cryptococcal meningitis
Fluconazole works well against Candida albicans, a common cause of yeast infections.
It’s also used to prevent fungal infections in people with weakened immune systems, like those undergoing stem cell transplants. Studies in the early 1990s showed that fluconazole was effective in preventing Candida albicans infections.
However, some Candida species, like Candida glabrata, are becoming more resistant to fluconazole. Research has found resistance in Candida albicans (10–13%), Candida tropicalis (5–19%), and Candida glabrata (36%).
Itraconazole
Itraconazole is used for a broader range of fungal infections, including:
- Aspergillosis
- Blastomycosis
- Histoplasmosis
- Nail fungus (onychomycosis)
It’s sometimes used to prevent fungal infections, especially Aspergillus, in immunocompromised patients.
Studies have shown that itraconazole can be better at preventing invasive mold infections. However, it can also cause more side effects, like liver problems and gastrointestinal issues.
One study pointed out that it’s important to weigh the benefits of itraconazole against its potential side effects when choosing an antifungal medication.
Adverse Effects and Tolerability
Like most medications, fluconazole and itraconazole can cause side effects, some of which can be serious, making it essential to understand the risks, warnings and precautions associated with itraconazole side effects.
Fluconazole
The most common side effects of fluconazole are:
- Nausea
- Vomiting
- Abdominal pain
- Headache
In rare cases, fluconazole can cause more serious side effects, such as liver toxicity and QT prolongation (an issue with the heart’s electrical activity). Doctors often monitor liver function with blood tests during longer courses of fluconazole therapy.
Overall, fluconazole is generally well-tolerated by most people.
Itraconazole
The most common side effects of itraconazole include:
- Nausea
- Vomiting
- Abdominal pain
- Rash
- Edema (swelling)
Serious side effects, though rare, can include liver toxicity, heart failure, and QT prolongation.
Studies have shown that itraconazole is more likely to cause liver problems than fluconazole. One study showed a tripling of baseline total bilirubin and transaminase levels in the itraconazole group.
Itraconazole also tends to be less well-tolerated than fluconazole, with higher rates of gastrointestinal issues and liver toxicity. In one study, 36% of participants discontinued itraconazole due to toxicity or intolerance, compared to only 16% in the fluconazole group.
Drug interactions
Both fluconazole and itraconazole interact with other medications, sometimes with serious consequences. So it’s important to let your doctor and pharmacist know about all the medicines you take — even over-the-counter drugs and supplements — before starting either of these antifungal treatments, and to ask about whether fluconazole and itraconazole are safe to combine.
Fluconazole drug interactions
Fluconazole has 571 known drug interactions. It moderately interacts with the CYP family of enzymes, specifically CYP2C9 and CYP2C19. That means fluconazole can cause the levels of some drugs, such as warfarin (a blood thinner) and phenytoin (an anti-seizure medicine), to rise in your body. Your doctor will likely monitor you more closely if you’re taking fluconazole with other medications.
Itraconazole drug interactions
Itraconazole has 548 known drug interactions. It has a strong interaction with CYP3A4, another enzyme in the CYP family. Because itraconazole strongly inhibits CYP3A4, it can cause a large number of medications to build up in your system. These include statins (cholesterol-lowering drugs), calcium channel blockers (blood pressure medications), and immunosuppressants (medicines that suppress the immune system).
Because of the risk of serious problems, itraconazole is contraindicated (meaning it should not be taken at all) with some medications. Your doctor will need to carefully review your medication list before prescribing itraconazole.
Even though fluconazole has more possible interactions, itraconazole interacts more strongly with other drugs and has a greater chance of causing a serious interaction.
Fluconazole and itraconazole: What about special populations?
Before you take fluconazole or itraconazole, it’s important to have a conversation with your healthcare provider about other health conditions and circumstances, such as pregnancy, kidney disease, or liver disease.
Pregnancy
If you are pregnant or trying to become pregnant, fluconazole should be used with caution, especially during the first trimester. Itraconazole should not be used during pregnancy due to the risk of harm to the developing baby.
Kidney disease
If you have kidney problems, your healthcare provider may need to adjust your fluconazole dosage. Itraconazole, on the other hand, doesn’t usually require a dosage adjustment. However, caution is advised if you have severe kidney problems.
Liver disease
If you have liver problems, both fluconazole and itraconazole should be used with caution, and your healthcare provider should monitor your liver function closely.
Antifungal Resistance
One thing to keep in mind when comparing fluconazole and itraconazole is that some fungi are becoming resistant to certain antifungal medications. This is especially true for certain Candida species, like Candida glabrata and Candida krusei, which are becoming resistant to fluconazole.
Azoles as a class of antifungals, especially fluconazole, are often used as a first-line treatment. But, with long-term use, the fungi can become resistant to the medication.
Itraconazole resistance can also happen, but it’s less common than fluconazole resistance in some Candida species.
When possible, your doctor should perform antifungal susceptibility testing to help guide treatment decisions. If the Candida is resistant to fluconazole or itraconazole, other antifungals, like echinocandins, may be needed.
Frequently Asked Questions
Can itraconazole damage kidneys?
While itraconazole is generally well-tolerated, kidney damage is a potential, though uncommon, side effect. It’s more likely to occur in individuals with pre-existing kidney conditions or those taking other medications that affect kidney function. Always discuss your medical history with your doctor before starting itraconazole.
How quickly does itraconazole work?
The speed at which itraconazole starts working varies depending on the type and severity of the fungal infection. Some superficial infections might show improvement within a few days, while more serious systemic infections could take weeks or even months to respond to treatment. Consistency with your prescribed dosage, such as following guidelines for itraconazole 200 mg dosage for adults, is key.
Is itraconazole best for fungal infection?
Whether itraconazole is the “best” antifungal depends entirely on the specific fungus causing the infection and its location in the body. Itraconazole is effective against a broad range of fungi, but other antifungals like fluconazole, voriconazole, or amphotericin B might be more appropriate for certain infections. Your doctor will determine the most suitable medication for your case.
Which antifungal is best for fungal infection?
There’s no single “best” antifungal for all fungal infections. The most effective medication depends on factors such as the type of fungus, the site of infection, the severity of the illness, and the patient’s overall health. A healthcare professional should always be consulted to determine the appropriate antifungal treatment.
What is strongest medication for fungal infection?
The “strongest” antifungal medication isn’t necessarily the best choice. While medications like amphotericin B are potent, they also carry a higher risk of side effects. The ideal treatment balances effectiveness with safety, and the decision should be made by a doctor based on the individual’s specific needs and medical history.
Wrapping Up
Fluconazole and itraconazole are both antifungal medications, but they have some key differences. Fluconazole is generally easier to tolerate and has fewer interactions with other medications, making it a solid first choice for some common yeast infections. Itraconazole can treat a wider range of fungal infections, but it’s also more likely to cause side effects and interact with other drugs.
When choosing between fluconazole and itraconazole, your doctor will consider the specific type of infection you have, your medical history, and any other medications you’re taking. Local resistance patterns can also play a role in which antifungal is more appropriate.
It’s important to get regular checkups and lab tests while taking antifungal medications. Monitoring for side effects and making sure the medication is still working against the infection are important for successful treatment.