People living with systemic lupus erythematosus (SLE) take an average of five medications, which may raise their risk for dangerous drug-drug interactions (side effects caused by taking multiple drugs at the same time). Sometimes, it may be difficult to tell whether you’re experiencing symptoms of lupus or side effects of a drug interaction.

“I haven’t been feeling like myself for a few weeks now. A lot of brain fog and feeling blahhh,” wrote one MyLupusTeam member. “Not sure if it’s from the lupus, or if the meds aren’t interacting well.

More than 2,000 MyLupusTeam members report having taken Cymbalta, a formulation of duloxetine. If you take duloxetine, do you know which medications it can interact with? Many — such as nonsteroidal anti-inflammatory drugs (NSAIDs) — are among those commonly taken by people with lupus.

What Is Cymbalta?

Cymbalta is a brand-name formulation of duloxetine, a medication commonly used to treat depression — which affects about 24 percent of people living with systemic lupus erythematosus. Duloxetine is used to treat certain kinds of pain, including neuropathic (nerve) pain. More than 48,000 members of MyLupusTeam report experiencing one or more types of pain as symptoms of their lupus.

Duloxetine belongs to the family of drugs called serotonin and norepinephrine reuptake inhibitors (SNRIs). It improves symptoms of depression by decreasing serotonin and norepinephrine reuptake receptor activity, which in turn increases the amount of serotonin and norepinephrine in the brain. Serotonin and norepinephrine are body chemicals that improve mood and energy, respectively.

Like many medications, duloxetine can interact with other drugs. Read on to learn about five of the most common drugs that can interact with formulations of duloxetine.

1. NSAIDs

NSAIDs stop the body’s production of proteins involved in inflammation. Inflammation results from the immune system activity that occurs in response to injury or infection. The most commonly used over-the-counter NSAIDs are ibuprofen (Advil or Motrin), aspirin, and naproxen (Aleve).

NSAIDs are used to treat the pain caused by inflammation. For people with lupus, NSAIDs can improve joint and muscle discomfort caused by chronic inflammation.

NSAIDs alone can have some serious side effects, including abnormal bleeding and worsening of kidney disease. This side effect is especially important to consider if someone has lupus since lupus nephritis — kidney disease caused by lupus — is common.

Studies show that when NSAIDs are combined with drugs that decrease serotonin reuptake, it can increase a person’s risk of bleeding in their upper gastrointestinal (GI) tract. The upper GI tract includes the esophagus, stomach, and the first part of the small intestine.

Most research that has studied this interaction focuses on selective serotonin reuptake inhibitors (SSRIs) and NSAID use because SSRIs are the most commonly used antidepressant. Like SNRIs, SSRIs work by increasing the amount of serotonin in the brain — but they affect only the brain’s serotonin reuptake receptors.

That said, several studies have found that venlafaxine (Effexor) — another SNRI — increases upper GI bleeding risk. Because duloxetine and venlafaxine have similar chemical effects, it’s reasonable to use caution when taking NSAIDs together with Cymbalta and other formulations of duloxetine.

Precautions are especially important in people with a history of bleeding issues, like peptic ulcer disease. Peptic ulcer disease results from open, bleeding wounds in the stomach or the first part of the small intestine.

2. Beta-Blockers

Beta-blockers are a family of drugs used to treat heart disease. They work by blocking the actions of epinephrine and norepinephrine on the cardiovascular system (heart and blood vessels), lowering heart rate and blood pressure. Along with increasing energy, norepinephrine and epinephrine activate the cardiovascular system.

Some examples of beta-blockers include:

• Atenolol (Tenormin)
• Carvedilol (Coreg)
• Metoprolol (Lopressor, Toprol XL)
• Nadolol (Corgard)
• Propranolol (Inderal LA)

Research shows that beta-blockers can interact with duloxetine because duloxetine decreases the activity of an enzyme that breaks down beta-blockers. Enzymes are proteins that speed up chemical reactions in the body, including drug breakdown in the liver.

By decreasing the breakdown of beta-blockers, duloxetine may increase beta-blocker effects. Adverse effects of beta-blockers may include low heart rate, low blood pressure, arrhythmia (abnormal heart rhythm), dizziness, drowsiness, and nausea.

Very low blood pressure, heart rate, and arrhythmia can be life-threatening. Anyone who experiences these symptoms while taking a beta-blocker and duloxetine should seek immediate medical advice from a health care professional.

3. Certain Antidepressants

Several categories of antidepressants interact with duloxetine. These interactions result from the impact of these drugs on serotonin levels. Because duloxetine and some other antidepressants increase serotonin levels, their combination can cause serotonin syndrome.

Serotonin syndrome results from high blood levels of serotonin. In severe cases, which can be life-threatening, serotonin syndrome can cause high fever, seizures, and passing out. For this reason, doctors are recommended to use caution when combining duloxetine with certain antidepressants. These include:

• SSRIs, including sertraline (Zoloft), fluoxetine (Prozac), and citalopram (Celexa)
• Other SNRIs, including venlafaxine
• Tricyclic antidepressants, including nortriptyline (Aventyl, Pamelor) and amitriptyline

The U.S. Food and Drug Administration (FDA) recommends against combining monoamine oxidase inhibitors (MAOIs) — another family of antidepressants that affect serotonin — in combination with duloxetine. This stronger recommendation is due to the high risk of severe serotonin syndrome.

4. Warfarin

Warfarin (previously sold under the brand name Coumadin) is a prescription drug used to prevent blood clots, known as an anticoagulant or blood thinner. It works by reducing vitamin K in the body, which is necessary for the blood clotting system to work.

Based on case reports, duloxetine may interact with warfarin by increasing bleeding risk. Although this risk hasn’t been found in research studies, the FDA still recommends that doctors monitor people closely who take these drugs together.

People who take warfarin get frequent blood testing to check how well it’s working. More frequent blood tests may be necessary when combining warfarin with duloxetine so that the warfarin dose can be changed if needed.

5. Fluoroquinolones

Fluoroquinolones are a category of antibiotics used to treat respiratory and urinary tract infections. The most commonly used fluoroquinolones are ciprofloxacin (Cipro), levofloxacin, and moxifloxacin (Avelox).

The FDA recommends that doctors be careful about combining fluoroquinolones with duloxetine. Because fluoroquinolones block an enzyme needed to break down duloxetine, taking them together will increase the amount of duloxetine in the blood. This higher drug level may lead to adverse effects of duloxetine, including serotonin syndrome. For this reason, treatment with this drug combination should be monitored closely or avoided, if possible.

Talk With Your Doctor

This article reviews some of the major interactions between duloxetine and other drugs, but there are others. Make sure all of the providers on your health care team have an updated list of all the medications — including those prescribed and available over the counter — and supplements you’re taking.

If you have concerns about potential interactions between duloxetine and other drugs you’re taking, talk with your doctor. They’ll review your medications and make sure you’re safe from dangerous interactions.

Connect With Others Who Understand

On MyLupusTeam — the social network for people with lupus and their loved ones — more than 223,000 members come together to ask questions, give advice, and share their stories with others who understand life with lupus.

Do you take multiple prescription drugs, including Cymbalta or another formulation of duloxetine, to manage your lupus? Share your experience in the comments below, or start a conversation by posting on your Activities page.