Why Itraconazole Drug Interactions Are a Big Deal

If there's one thing you need to know about Itraconazole, it's this: it interacts with a lot of other medications. Some of these interactions are so dangerous that certain drug combinations are completely off-limits.

Itraconazole carries an FDA boxed warning — the most serious type of drug warning — specifically about drug interactions. Taking Itraconazole with certain other medications can cause life-threatening heart rhythm problems, including sudden cardiac death.

This guide will walk you through the most important interactions, explain why they happen, and tell you exactly what to discuss with your doctor before starting Itraconazole. For background on the medication itself, see our overview on what Itraconazole is and how it's used.

How Itraconazole Causes Drug Interactions

To understand the interactions, it helps to know a little about how your body processes medications.

Your liver uses enzymes to break down (metabolize) drugs. One of the most important of these enzymes is called CYP3A4. This single enzyme is responsible for breaking down roughly 50% of all medications on the market.

Itraconazole is a strong inhibitor of CYP3A4. That means when you take Itraconazole, it slows down CYP3A4, which causes other medications that rely on this enzyme to build up to higher-than-normal levels in your blood. Higher drug levels can mean more intense effects — including dangerous side effects.

As we explain in our article on how Itraconazole works, this CYP3A4 inhibition is a side effect of how Itraconazole targets fungal enzymes — it doesn't perfectly distinguish between fungal and human CYP enzymes.

Medications You Must NEVER Take With Itraconazole

These combinations are contraindicated — meaning they should never be used together under any circumstances:

Heart Rhythm Medications

• Quinidine — Risk of QT prolongation, torsades de pointes, and sudden death
• Dofetilide — Same risk of fatal heart rhythm disturbances
• Dronedarone — Increased levels leading to cardiovascular toxicity
• Disopyramide — Risk of serious cardiac arrhythmias

Certain Psychiatric/Neurological Medications

• Pimozide — Risk of QT prolongation and fatal cardiac arrhythmias
• Oral Midazolam and Triazolam — Risk of prolonged, potentially life-threatening sedation
• Levacetylmethadol (Levomethadyl) — Risk of cardiac toxicity

Cholesterol Medications

• Simvastatin (Zocor) — Greatly increased risk of rhabdomyolysis (severe muscle breakdown that can cause kidney failure)
• Lovastatin (Mevacor) — Same rhabdomyolysis risk

Ergot Alkaloids

• Ergotamine and Dihydroergotamine — Risk of ergotism (severe blood vessel constriction that can lead to gangrene)

Other Contraindicated Medications

• Cisapride — Risk of fatal cardiac arrhythmias
• Nisoldipine and Felodipine — Excessive blood pressure lowering and heart effects
• Ivabradine — Increased levels leading to bradycardia
• Methadone — Risk of QT prolongation

Medications That Need Caution or Dose Adjustments

These medications can be used with Itraconazole in some cases, but require careful monitoring, dose adjustments, or your doctor's specific approval:

Blood Thinners

• Warfarin (Coumadin) — Itraconazole increases warfarin's effect, raising your bleeding risk. Your doctor will need to monitor your INR more frequently and may reduce your warfarin dose.

Heart and Blood Pressure Medications

• Digoxin — Itraconazole increases digoxin levels. Your doctor should monitor digoxin blood levels and watch for toxicity signs (nausea, vision changes, slow heart rate).
• Calcium channel blockers (like amlodipine, diltiazem, verapamil) — Increased levels can cause excessive blood pressure lowering, edema, and heart failure risk.

Immunosuppressants

• Cyclosporine, Tacrolimus, Sirolimus — Itraconazole significantly increases levels of these transplant medications. Blood level monitoring and dose reductions are essential.

Other Statins

• Atorvastatin (Lipitor) — Can be used with caution at the lowest possible dose with monitoring for muscle pain. (Remember: Simvastatin and Lovastatin are completely contraindicated.)

Corticosteroids

• Budesonide, Fluticasone, Methylprednisolone — Itraconazole can increase corticosteroid levels, potentially causing Cushing syndrome (weight gain, moon face, high blood sugar) even from inhaled steroids.

Pain Medications

• Fentanyl and Oxycodone — Itraconazole can increase opioid levels, raising the risk of respiratory depression (dangerously slow breathing). Dose adjustments may be needed.

Chemotherapy Drugs

• Busulfan, Docetaxel, Vinca alkaloids — Increased chemotherapy toxicity. Oncologists must carefully manage these combinations.

Other Medications

• Alprazolam (Xanax) — Increased sedation
• Buspirone — Increased levels and side effects
• Cilostazol — Dose must be reduced
• Eletriptan (migraine medication) — Avoid within 72 hours of Itraconazole
• Oral hypoglycemics (diabetes medications) — Increased risk of hypoglycemia (low blood sugar)

Medications That Reduce Itraconazole's Effectiveness

Some medications work the other way — they make Itraconazole less effective by speeding up its breakdown in the liver:

• Rifampin and Rifabutin — Can reduce Itraconazole levels so much that the antifungal stops working
• Phenytoin, Carbamazepine, Phenobarbital — Anti-seizure medications that dramatically lower Itraconazole blood levels
• Proton pump inhibitors (omeprazole, pantoprazole, etc.) — Reduce stomach acid, which decreases absorption of Itraconazole capsules
• H2 blockers (famotidine, ranitidine) — Same acid-reducing effect that impairs capsule absorption
• Antacids — Should be taken at least 2 hours apart from Itraconazole capsules

If you take any of these medications, your doctor may need to choose a different antifungal or find a workaround.

Food and Beverage Interactions

Itraconazole also interacts with some foods and drinks:

• Grapefruit and grapefruit juice — Can increase Itraconazole levels (CYP3A4 inhibition). Best to avoid.
• Alcohol — Both Itraconazole and alcohol can affect the liver. Excessive alcohol increases the risk of liver damage — a known side effect of Itraconazole.
• Cola beverages — Interestingly, cola can actually help absorption of Itraconazole capsules in patients with low stomach acid, due to its acidity.

What to Tell Your Doctor Before Starting Itraconazole

Before your doctor prescribes Itraconazole, make sure they have a complete picture of everything you take:

• All prescription medications — Even ones prescribed by other doctors
• Over-the-counter medications — Including antacids, pain relievers, and allergy medications
• Supplements and vitamins — Some herbal products (like St. John's Wort) can affect drug metabolism
• Recreational substances — Including alcohol use

Don't be embarrassed or skip anything. Your pharmacist also reviews for interactions when filling your prescription, but they can only catch problems with medications they know about.

What to Do If You're Already Taking a Medication That Interacts

If you discover a potential interaction with a medication you're already taking:

1. Don't stop either medication on your own — Suddenly stopping some medications can be dangerous
2. Contact your doctor or pharmacist immediately — They can evaluate the risk and decide on the best course of action
3. Your doctor may: Adjust doses, temporarily pause one medication, switch to a different antifungal, or increase monitoring

If Itraconazole isn't safe with your current medications, there are alternative antifungal options that may have fewer interactions.

Finding and Affording Itraconazole

Once you and your doctor have confirmed Itraconazole is safe with your other medications, you'll need to fill your prescription. Use MedFinder to check pharmacy stock or see our guide on finding Itraconazole in stock near you. For cost savings, read our guide on Itraconazole coupons and discounts.

If you're having trouble with supply, learn about the current shortage situation and why Itraconazole can be hard to find. Need a prescriber? See our guide on finding a doctor who prescribes Itraconazole.

Healthcare providers can find additional resources in our provider guides on shortage management, helping patients find stock, and cost-saving strategies for patients.

Bottom Line

Itraconazole is an effective antifungal, but its long list of drug interactions demands careful attention. Several medication combinations are outright dangerous and must be avoided. Always give your doctor and pharmacist a complete list of everything you take, and don't start or stop any medications during Itraconazole treatment without checking first. Your safety depends on it.