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Duloxetine interactions to avoid

Certain duloxetine interactions may increase the risk of side effects, including the increased risk of serotonin syndrome
Gerardo Sison medical writer headshot
By | Oct. 6, 2023
Rx pill bottle and prescription pad: Duloxetine interactions

Key takeaways

  • Duloxetine, marketed as Cymbalta, is an antidepressant used for treating major depressive disorder, anxiety, neuropathic pain, fibromyalgia, and chronic pain. It can interact with several medications, increasing the risk of side effects like serotonin syndrome.

  • Major concerns include interactions with monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), other SNRIs, tricyclic antidepressants, opioids, amphetamines, certain antiarrhythmics, NSAIDs, certain antibiotics, and warfarin, which can lead to severe side effects or diminished effectiveness of the medication.

  • Duloxetine can interact with foods and beverages; while it can be taken with or without food, combining it with large amounts of alcohol is not recommended due to an increased risk of liver injury, and there’s limited research on its interaction with caffeine.

  • To minimize the risk of duloxetine interactions, consult your healthcare provider before starting treatment to discuss your current medications and stay vigilant for potential warning signs of drug interactions.

In this article:

Duloxetine, known by its brand name Cymbalta, is a prescription medication used for mental health conditions and chronic pain. More specifically, it is a type of antidepressant called a serotonin-norepinephrine reuptake inhibitor (SNRI). Duloxetine works by increasing certain chemicals in the brain, which may help improve mood and relieve pain. It mainly treats major depressive disorder, generalized anxiety disorder in adults, neuropathic pain, fibromyalgia, and chronic pain conditions. 

Although duloxetine is an effective medication, it may interact with certain medications, leading to changes in how the drug is absorbed, processed, or metabolized in the body. Some duloxetine interactions may increase the risk of side effects, while others could reduce the medication’s therapeutic benefits. Some side effects of taking Cymbalta include drowsiness, constipation, dry mouth, loss of appetite, and weight loss. You may want to discuss your medications with a healthcare provider and be aware of potential duloxetine interactions and allergic reactions. That way, you can ensure the safety and effectiveness of the drug. 

Duloxetine-drug interactions

Duloxetine can interact with various medications, including prescription drugs, over-the-counter medicines, and herbal supplements. One of the major concerns of interactions is an increased risk of serotonin syndrome caused by increased serotonin levels in the brain. Symptoms of serotonin syndrome include agitation, confusion, rapid heart rate, and high blood pressure. Some common drug classes duloxetine may interact with include opioids, other antidepressants, and certain antibiotics.

Monoamine oxidase inhibitors (MAOIs)

Monoamine oxidase inhibitors (MAOIs) are a class of drugs that may have severe interactions with duloxetine. MAOIs are usually prescribed to treat depression and could lead to serious side effects, such as potentially life-threatening serotonin syndrome, when combined with duloxetine. Other medications, such as methylene blue and the antibiotic linezolid, can also act as MAOIs in the body and should be avoided with duloxetine due to the risk of serotonin syndrome. Examples of MAOIs include:

  • Nardil (phenelzine)
  • Eldepryl (selegiline)
  • Parnate (tranylcypromine)
  • Zyvox (linezolid)
  • Provayblue (methylene blue)

Avoid taking duloxetine if you are currently or have recently taken an MAOI within the past two weeks. In addition, wait at least five days after stopping duloxetine before starting an MAOI.

Selective serotonin reuptake inhibitors (SSRIs)

Duloxetine may interact with selective serotonin reuptake inhibitors (SSRIs), primarily used to treat depression and anxiety. Combining duloxetine with these drugs can increase the risk of side effects and serotonin syndrome. Examples of common SSRIs include:

  • Prozac (fluoxetine)
  • Luvox (fluvoxamine)
  • Paxil (paroxetine)
  • Zoloft (sertraline)

Inform your healthcare provider if you are taking an SSRI; dosage adjustments for one or both medications might be needed in such cases.

Serotonin and norepinephrine reuptake inhibitors (SNRIs)

Taking duloxetine with other serotonin and norepinephrine reuptake inhibitors (SNRIs) can increase the risk of side effects and serotonin syndrome. Common SNRIs include:

  • Effexor (venlafaxine)
  • Pristiq (desvenlafaxine)

A healthcare provider should be consulted before taking duloxetine with another SNRI, as they may need to adjust dosages or recommend alternative medications.

Tricyclic antidepressants

Taking duloxetine with tricyclic antidepressants can lead to increased serotonin levels in the brain. As a result, this interaction can cause an increased risk of side effects and serotonin syndrome. Common tricyclic antidepressants include:

  • Elavil (amitriptyline)
  • Tofranil (imipramine)
  • Pamelor (nortriptyline)

A healthcare provider may need to adjust dosages or recommend alternative medications to avoid an interaction.

Opioids

Combining duloxetine with opioids may result in an increased risk of serotonin syndrome. Examples of opioids include:

  • OxyContin (oxycodone)
  • Vicodin (hydrocodone)
  • Morphine (morphine)
  • Actiq (fentanyl)
  • Ultram (tramadol)

A healthcare provider may need to monitor you closely or recommend alternative treatments if you take opioids and duloxetine.

Amphetamines

Amphetamines may have serotonergic effects. As a result, taking duloxetine with amphetamines can increase the risk of serotonin syndrome. Common amphetamines include:

  • Adderall (amphetamine and dextroamphetamine)
  • Ritalin (methylphenidate)
  • Vyvanse (lisdexamfetamine)

A healthcare provider may need to adjust dosages or recommend other medications to avoid an interaction between duloxetine and amphetamines.

Certain antiarrhythmics

Using duloxetine with certain antiarrhythmics like propafenone, flecainide, and quinidine may increase the risk of cardiac side effects. The combined effect of these medications could result in undesirable changes in heart rhythm. Common antiarrhythmics include:

  • Rythmol (propafenone)
  • Tambocor (flecainide)
  • Quinidex (quinidine)

A healthcare provider should be consulted before taking duloxetine with any of these antiarrhythmics, as they may need to monitor your heart function or recommend alternative treatments closely.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Duloxetine interacts with nonsteroidal anti-inflammatory drugs (NSAIDs), which are used for pain and inflammation. When combined with duloxetine, NSAIDs may increase the risk of gastrointestinal bleeding. Examples of NSAIDs include:

  • Naprosyn, Aleve (naproxen)
  • Advil (ibuprofen)
  • Cataflam (diclofenac)
  • Celebrex (celecoxib)
  • Aspirin

Certain antibiotics

Combining duloxetine with certain antibiotics like ciprofloxacin or enoxacin may increase the levels of duloxetine in your blood, raising the risk of side effects. These antibiotics can inhibit liver enzymes that break down duloxetine. Antibiotics that interact with duloxetine include:

  • Cipro (ciprofloxacin)
  • Penetrex (enoxacin)

A healthcare provider should be consulted before taking duloxetine with these antibiotics, as they may need to adjust dosages or suggest alternative treatments.

Coumadin (warfarin)

Duloxetine may interact with warfarin, an anticoagulant medication. Combining both drugs can increase the risk of bleeding problems. If you are taking warfarin, you may need to monitor your international normalized ratio (INR) more closely when initiating or discontinuing duloxetine therapy.

Tagamet (cimetidine)

Using cimetidine alongside duloxetine can alter the metabolism of duloxetine, potentially leading to increased side effects. Cimetidine can block liver enzymes responsible for metabolizing duloxetine, which can cause increased duloxetine levels.

Duloxetine-food interactions

Duloxetine may interact with certain foods and beverages. Although the Food and Drug Administration (FDA) label states that duloxetine can be taken with or without food, eating a meal may prolong how long it takes for duloxetine to reach maximum levels in the body. 

Duloxetine and alcohol

It is not recommended to take duloxetine and consume large amounts of alcohol together. Duloxetine may worsen liver problems. In addition, excessive alcohol use with duloxetine is associated with an increased risk of liver injury. Therefore, duloxetine should not be used in those with chronic alcohol use or liver disease. Alcohol may also worsen the symptoms of depression and anxiety, two of the primary conditions that duloxetine treats.

Duloxetine and caffeine

There is limited research on the interaction between duloxetine and caffeine. However, consuming moderate amounts of caffeine, such as coffee, is generally considered safe while taking this medication. You may want to monitor your reaction to caffeine and discuss any concerns with a healthcare provider. Consuming excessive amounts of caffeine may worsen anxiety symptoms or interact with other medications.

Other duloxetine interactions

Duloxetine may interact with other substances like dietary supplements and herbal remedies. Duloxetine may interact with substances such as:

  • Tryptophan: Tryptophan is an amino acid that supports the production of serotonin. Taking duloxetine with tryptophan supplements may increase the risk of serotonin syndrome. 
  • St. John’s wort: Combining St. John’s Wort with duloxetine may also lead to an increased risk of serotonin syndrome. The herbal remedy is known to have serotonergic effects, which can amplify the effects of duloxetine.

Consult a healthcare provider about any supplements or herbal remedies you take before starting treatment with duloxetine. Certain supplements may require dosage adjustments or discontinuation of one of the substances.

Other considerations

Although duloxetine can be a useful treatment option, it may be associated with certain health precautions in people with various health conditions. Duloxetine may need to be monitored or altered in people with the following conditions:

  • Diabetes: Duloxetine may affect blood sugar levels. If you have diabetes, you may need to monitor your condition and discuss changes to your diabetes medications with a healthcare provider.
  • High blood pressure: The medication has been known to increase blood pressure in some people. Those with existing high blood pressure may require closer monitoring and adjustments to blood pressure medications.
  • Seizures: People with a history of seizures should exercise caution when taking duloxetine. The medication is associated with an increased risk of seizures.
  • Conditions that slow gastric emptying: The enteric coating on duloxetine delayed-release capsules may not dissolve properly in individuals with conditions that slow gastric emptying, leading to an increased risk of side effects or reduced effectiveness.
  • Bipolar disorder: Individuals with bipolar disorder may have an increased risk of mania or hypomania when taking duloxetine. A healthcare provider may recommend a mood stabilizer along with duloxetine or suggest an alternative treatment.
  • Suicidal thoughts: Duloxetine warns about an increased risk of suicidal thoughts and behaviors, particularly in children, adolescents, and young adults.  

If you have a current medical history of these or other medical conditions, consult your healthcare provider for medical advice before starting duloxetine treatment.

How to minimize duloxetine interactions

Duloxetine may be associated with several interactions. However, you may be able to minimize the risk of interactions by taking certain precautions. Before starting duloxetine treatment, consult a healthcare professional for medical advice, especially if you take multiple medications. They can assess the potential risks and benefits of the medication, taking into account any other medications you’re currently taking. Maintain a list of all the medications you take, including:

  • Prescription medications
  • Over-the-counter drugs
  • Herbal supplements
  • Vitamins and minerals

A healthcare provider may adjust dosages, discontinue medications, or recommend alternative treatments to minimize the risk of interactions. If changes are made to your medication regimen, follow your healthcare provider’s instructions.

Stay vigilant for potential warning signs of drug interactions while on duloxetine. Some common indicators may include:

  • Unexpected side effects
  • New symptoms or worsening of existing symptoms

Discuss any concerns you have about drug interactions with your healthcare providers, including pharmacists, primary care doctors, and mental health professionals. Providing updates about any medication changes can help them detect any potential interactions and address them appropriately.

When to talk to a healthcare provider about duloxetine interactions

You should speak with your healthcare provider about duloxetine interactions during the initial visit when they prescribe the medication. In addition, you can also consult your local pharmacist if you have concerns about drug interactions. In general, you should discuss interactions with your healthcare provider if you:

  • Take any prescription or over-the-counter medications
  • Use any dietary supplements or herbal products
  • Have any medical conditions or a history of certain illnesses
  • Experience any unexpected adverse effects or changes in health

This is not a complete list of duloxetine interactions. Discuss your overall medical history, including medical conditions and other medications you take, with your healthcare provider before starting treatment.