Hydroxychloroquine Interactions: 10 Things to Watch For

Hydroxychloroquine (Plaquenil) is a medication that’s approved to treat malaria, rheumatoid arthritis (RA), and lupus. It received a lot of attention in 2020 as a potential treatment for COVID-19. But the FDA doesn’t recommend it for this use. 

If you take hydroxychloroquine, you should know about its possible drug interactions. Some interactions only need extra monitoring, while others can be serious. 

The list below isn't a complete list of hydroxychloroquine interactions. Always talk with your healthcare provider and pharmacist before starting a new medication. It’s a good idea to give them your current medication list, too. This will help them check for possible hydroxychloroquine interactions.

1. Medications that affect heart rhythm

Some medications, including hydroxychloroquine, can affect your heart rhythm and lead to abnormal heartbeats (arrhythmias). 

Hydroxychloroquine may cause arrhythmias by making the QT interval longer. The QT interval is a period of time when the heart rests after beating. If you take hydroxychloroquine with other medications that prolong the QT interval, the risk of arrhythmia is higher. 

Other medications that can prolong the QT interval include:

• Macrolide antibiotics like azithromycin (Zithromax)

• Fluoroquinolone antibiotics like ciprofloxacin (Cipro)

• Antiarrhythmic medications like amiodarone (Pacerone)

• Antipsychotics like ziprasidone (Geodon)

• Tricyclic antidepressants like amitriptyline

• Opioids like methadone (Methadose)

Combining hydroxychloroquine with these medications isn’t recommended. Before starting hydroxychloroquine, talk to your healthcare provider or pharmacist. Ask if any of your other medications could cause arrhythmias. You’ll also want to let them know if you have an existing heart condition.

If you’re taking hydroxychloroquine and you experience signs of an abnormal heartbeat, seek emergency care. Signs include lightheadedness, sudden fainting, and blurred vision.

2. Diabetes medications

Medications that treat diabetes often work by lowering blood sugar. Diabetes medications include oral pills like metformin and glipizide and injectable medications like liraglutide (Victoza), exenatide (Byetta, Bydureon BCise), and insulin. 

Hydroxychloroquine can also cause low blood sugar (hypoglycemia). So when it’s combined with other medications that lower blood sugar, severe hypoglycemia is possible. Symptoms of hypoglycemia include a fast heartbeat, sweating, and shakiness. If hypoglycemia isn’t treated, it can lead to seizures, coma, and even death.

If you need to take hydroxychloroquine and diabetes medications together, your healthcare provider may lower the dose of your diabetes medications. Still, watch for symptoms of hypoglycemia. And follow your provider’s instructions for checking your blood sugar at home. 

If you develop hypoglycemia, you can treat it quickly with a fast-acting sugar source. Examples include ½ cup of fruit juice or regular soda. You could also take 4 glucose tablets. 

After treating hypoglycemia at home, contact your healthcare provider right away. They’ll let you know if you need to do anything else.

3. Medications that increase seizure risk

Hydroxychloroquine lowers the “seizure threshold” and makes a seizure more likely. The lower the seizure threshold is, the more likely you are to experience a seizure.

Many other medications may lower the seizure threshold, too. Combining hydroxychloroquine with these medications increases your risk of seizures. Examples include:

• Some antidepressants like bupropion (Wellbutrin SR, Wellbutrin XR) and amitriptyline

• Antipsychotics like clozapine (Clozaril)

• Tramadol (ConZip)

• Diphenhydramine (Benadryl)

Ask your healthcare provider or pharmacist if you take any medications that lower the seizure threshold. And let them know if you’ve had seizures in the past. If you’re at high risk of seizures, you and your provider can discuss the risks and benefits of hydroxychloroquine.

4. Seizure medications

Seizure medications help prevent seizures. People with conditions like epilepsy often take seizure medications. 

As discussed above, hydroxychloroquine may lower the seizure threshold. But it can also interact with many seizure medications, including:

• Carbamazepine (Tegretol, Carbatrol) 

• Oxcarbazepine (Trileptal, Oxtellar XR)

• Lacosamide (Vimpat)

• Lamotrigine (Lamictal)

• Phenytoin (Dilantin, Phenytek)

• Phenobarbital

These medications may not work as well when taken with hydroxychloroquine. Many of them may also affect how well hydroxychloroquine works.

If you’re taking a seizure medication, talk to your healthcare provider before starting hydroxychloroquine. They can help you weigh the risks and benefits of this medication.

5. Antacids

Antacids are over-the-counter (OTC) medications that help treat symptoms of acid reflux, like heartburn. They work by neutralizing stomach acid. Common examples include calcium carbonate/magnesium hydroxide (Rolaids) and calcium carbonate (Tums). 

Antacids may affect the absorption of hydroxychloroquine. This can make it less effective by lowering medication levels in the body. 

We don’t have much research on this interaction, however. Most of the research is with chloroquine, a medication that’s similar in structure to hydroxychloroquine. It’s recommended to separate chloroquine from antacids by at least 4 hours. So it may be a good idea to follow these instructions for hydroxychloroquine, too.

6. Cimetidine

Cimetidine (Tagamet HB) is a medication that treats heartburn and gastroesophageal reflux disease (GERD). It’s part of a group of medications called histamine-2 antagonists (H2 blockers). H2 blockers lower the amount of acid made in your stomach. A less acidic stomach can help relieve symptoms of heartburn and GERD. 

Cimetidine can block the breakdown and clearance of hydroxychloroquine. This may cause high levels of hydroxychloroquine to build up in the body, which can increase side effects. Possible side effects include nausea, diarrhea, and blurry vision. More serious side effects include permanent eye damage and muscle weakness.

It’s best to avoid combining hydroxychloroquine and cimetidine. If you need hydroxychloroquine, your healthcare provider may suggest another H2 blocker like famotidine (Pepcid AC, Zantac 360) instead.

7. Cyclosporine

Cyclosporine (Sandimmune) is an immunosuppressant medication. It’s often prescribed after an organ transplant. Hydroxychloroquine can raise the levels of cyclosporine in the body. This can cause worse cyclosporine side effects. These include kidney problems, high blood pressure, and infection.

If you take cyclosporine and hydroxychloroquine, your healthcare provider will monitor your blood levels of cyclosporine more closely. And they may lower your dose of cyclosporine if your levels are too high. They may also suggest an alternative to hydroxychloroquine to avoid this interaction altogether.

8. Methotrexate

Methotrexate (Trexall, Rasuvo) is used to treat many inflammatory conditions. Examples include rheumatoid arthritis (RA), psoriasis, and more. It’s also used to treat various types of cancer. 

Hydroxychloroquine and methotrexate may be used together to treat RA. This combination can make methotrexate more potent and increase its effectiveness. But it also may raise the risk of side effects. Mouth sores, diarrhea, and kidney problems may be more likely.

If your healthcare provider has prescribed hydroxychloroquine and methotrexate together, they’ll likely monitor your kidney function and various blood tests regularly. 

9. Remdesivir

Remdesivir (Veklury) is an injectable medication that treats COVID-19. It’s an antiviral that’s given in a clinic or hospital. It works by preventing SARS-CoV-2, the virus that causes COVID-19, from making copies of itself. This prevents it from growing. 

In June 2020, the FDA issued a warning that remdesivir may not work as well in people taking hydroxychloroquine. If you need both these medications, your healthcare provider can help you manage this potential interaction. Or they may ask you to stop taking hydroxychloroquine for the short time you’re taking remdesivir.

10. Digoxin

Digoxin (Lanoxin) treats conditions like heart failure and atrial fibrillation. It slows your heart rate so more blood and oxygen can pump from the heart to the rest of the body.  

Digoxin is considered a “narrow therapeutic index” medication. This means that small changes to your digoxin dose can have a big impact. Even a slightly higher dose could cause dangerous side effects.

Hydroxychloroquine can raise levels of digoxin in the body. In serious cases, this can cause digoxin toxicity. Signs of digoxin toxicity include changes to vision, nausea and vomiting, and an abnormally slow heart rate. 

If you need hydroxychloroquine while taking digoxin, your healthcare provider may monitor your blood levels of digoxin to make sure they aren’t too high. Or they may recommend alternatives to either digoxin or hydroxychloroquine to avoid the interaction altogether.

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Written by:

Austin Ulrich, PharmD, BCACP

​​Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. Ulrich’s experience includes direct patient care in hospital and community pharmacies.

Edited by:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

Reviewed by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

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