10 Oral Ketoconazole Interactions You Should Know About

Ketoconazole is an antifungal medication that treats a variety of infections. It comes in an oral tablet form and topical forms, including a cream, foam (Extina), and shampoo (Nizoral).

Oral ketoconazole tablets have been around for many years. But this form isn’t prescribed as much as the topical products. This is because it carries a risk of liver damage, along with having many potential drug interactions. The topical forms are absorbed less by the body, so they don’t have the same risks. 

Oral ketoconazole can affect liver enzymes (proteins) that are responsible for breaking down medications. In some cases, ketoconazole can raise the level of a medication in your body. In others, ketoconazole levels are affected. Some interactions should be avoided altogether, while others can be managed with dosage adjustments.

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To avoid or manage ketoconazole interactions in advance, be sure to share your current medication list with your healthcare team. Below, we cover 10 notable oral ketoconazole interactions.

1. Medications that lower acidity in the stomach

Ketoconazole needs an acidic environment in the stomach to be absorbed. Medications that lower acidity in the stomach can reduce ketoconazole absorption.

There are quite a few medications that lower acidity in the stomach, and many are available over the counter (OTC). These medications are often used for relief of occasional heartburn or to treat gastroesophageal reflux disease (GERD). Antacids, histamine-2 antagonists (H2 blockers), and proton pump inhibitors (PPIs) are some common examples. 

Examples of individual medications within these classes are listed in the table below.

If you need to take one of these medications with ketoconazole, your healthcare team can instruct you on how to manage a potential interaction. Their instructions may include:

• If you’re taking an antacid: Take your antacid at least 1 hour before or 2 hours after ketoconazole.

• If you’re taking an H2 blocker or PPI: Drink an acidic beverage, such as non-diet cola, with your ketoconazole doses to help with absorption.

2. Tamsulosin (Flomax)

Tamsulosin (Flomax) is an alpha blocker that’s used to treat symptoms of benign prostatic hyperplasia (BPH), or an enlarged prostate. When combined with oral ketoconazole, tamsulosin’s levels can increase in the body. This may raise the risk of tamsulosin side effects such as dizziness, headaches, and blood pressure changes. Due to these risks, this combination should be avoided.

3. Opioids

Opioids are pain medications used for treating moderate-to-severe pain. Ketoconazole can interact with some opioids, blocking them from being broken down in the body. This can increase the risk of side effects such as drowsiness, slowed breathing, and overdose.

Examples of opioids that can interact with ketoconazole include oxycodone (Roxicodone, OxyContin), fentanyl, and methadone. It’s best to avoid taking these opioids while taking ketoconazole. Your prescriber can recommend treatment options that are less likely to interact with ketoconazole.

4. Heart rhythm medications

Antiarrhythmics are used to treat heart conditions like atrial fibrillation. Ketoconazole can increase levels of some antiarrhythmics in the body. This can raise the risk of side effects such as dizziness and lightheadedness. Serious heart rhythm problems are also possible.

Antiarrhythmics that can interact with ketoconazole include:

• Disopyramide (Norpace)

• Dofetilide (Tikosyn)

• Dronedarone (Multaq)

• Quinidine

• Digoxin (Lanoxin)

• Amiodarone (Pacerone)

Most of these medications should be avoided while taking ketoconazole. With digoxin, your prescriber may be able to manage a possible interaction by monitoring your blood levels more often. And, if needed, they may adjust your dosage.

5. Anticoagulants

Anticoagulants are medications that help treat and prevent blood clots. Ketoconazole can increase the levels of some anticoagulants in the body. This can raise the risk of certain side effects, including bleeding. Rivaroxaban (Xarelto), dabigatran (Pradaxa), and warfarin (Jantoven), and apixaban (Eliquis) are known to interact with ketoconazole.

Your prescriber will likely try to avoid combining any of these anticoagulants with ketoconazole. Or they may recommend taking a lower dosage or doing close monitoring. Tell your prescriber right away if you notice unusual bleeding or bruising while taking an anticoagulant and ketoconazole.

6. Migraine medications

Certain migraine medications can also interact with ketoconazole. Ketoconazole can increase the level of these medications in the body. And this can raise the risk of side effects such as dizziness and nausea.

Ergot derivatives are a group of migraine medications that should be avoided with ketoconazole. Examples include ergotamine (Ergomar) and dihydroergotamine (Migranal). Combining these medications with ketoconazole can severely impair blood flow to the brain and extremities. 

Eletriptan (Relpax) is part of a large group of medications called triptans. Eletriptan shouldn’t be taken within at least 72 hours of ketoconazole.

Your prescriber will likely recommend a migraine medication that has a lower chance of interacting with ketoconazole. There are several other effective options for migraine treatment.

7. Mental health medications

There are a wide range of mental health medications that treat conditions such as depression, anxiety, and schizophrenia. Ketoconazole increases the levels of some mental health medications that are processed by liver enzymes. Examples include:

• Antipsychotics such as lurasidone (Latuda), aripiprazole (Abilify), and quetiapine (Seroquel)

• Benzodiazepines such as alprazolam (Xanax) and triazolam (Halcion)

• Buspirone

Combining these medications with ketoconazole can increase the risk of their side effects. In some cases, a lower dosage of the mental health medication can help manage a potential interaction. Other medications should be avoided altogether with ketoconazole.

8. Calcium channel blockers

Calcium channel blockers (CCBs) are a common group of blood pressure medications. Many CCBs can interact with ketoconazole. Some examples are amlodipine (Norvasc), felodipine ER, and verapamil. 

Taking these CCBs with oral ketoconazole can increase the risk of side effects such as fluid buildup (edema), a slowed heart rate, and low blood pressure. In some cases, you may be able to take a lower CCB dose with ketoconazole to manage this interaction. Or your prescriber may try to find treatment options that are less likely to interact.

9. Transplant medications

Transplant medications are used to lower the risk of organ transplant rejection. There are many different transplant medications, and some of them can interact with ketoconazole. Examples of these medications include:

• Calcineurin inhibitors (CNIs) such as tacrolimus (Prograf) and cyclosporine (Sandimmune)

• Antiproliferative agents such as sirolimus (Rapamune) and everolimus (Afinitor)

• Corticosteroids such as methylprednisolone (Medrol) and dexamethasone (Taperdex, Hemady)

Ketoconazole can increase the level of these medications in the body, raising the risk of side effects. Some of these interactions can be managed with a lower transplant medication dosage and close blood level monitoring. But make sure your transplant team is aware of any new medications you’ve been prescribed.

10. Statins

Statins are common medications for treating high cholesterol. There are many statins available, some of which can interact with ketoconazole. Examples of these medications include atorvastatin (Lipitor), lovastatin, and simvastatin (Zocor).

Ketoconazole can prevent the liver from breaking down these statins. This can increase the risk of side effects such as muscle pain and severe muscle damage that leads to rhabdomyolysis.

Lovastatin and simvastatin should be avoided with ketoconazole. If you’re taking one of these medications, your prescriber may have you stop taking it when you start ketoconazole. If you’re taking atorvastatin, your prescriber may lower your dosage of the medication. Other statins, such as rosuvastatin (Crestor), don’t interact with ketoconazole.

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Written by:

Austin Ulrich, PharmD, BCACP

Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. In his early career, he provided direct patient care in a variety of settings, including hospital and community pharmacies, and in a primary care clinic as a clinical pharmacist.

Edited by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

Reviewed by:

Stacey McCoy, PharmD, MS, BCPS

Stacey McCoy is a clinical pharmacy specialist with over 20 years of experience in various practice areas, including nearly 13 years as an emergency medicine specialist.

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