Does Duloxetine interact with other medications? (3+ tips)

In this article, we will answer the question, “Does Duloxetine interact with other medications?”. We will discuss some medications that have a strong interaction with Duloxetine. We will also discuss some measures to minimize or prevent drug interactions with Duloxetine.

Does Duloxetine interact with other medications?

Yes, Duloxetine does interact with other medications. Duloxetine tends to interact with many different medications to produce an array of side effects. These side effects may range from mild to extremely severe.

Duloxetine (also known as Cymbalta) is an antidepressant belonging to the class of serotonin and norepinephrine reuptake inhibitors (SNRIs) and is approved by the FDA for the treatment of major depressive disorder (MDD), generalised anxiety disorder (GAD), fibromyalgia (FM), and nerve, bone and joint pain (1). 

Duloxetine may interact with many medications, a few of which are as follows:

  • Selective serotonin reuptake inhibitors (SSRIs)
  • Other SNRIs
  • Monoamine oxidase inhibitors (MAOIs)
  • Antiplatelet medication
  • Anticonvulsants
  • Benzodiazepines
  • Triptans

What are some potential drug interactions with Duloxetine?

Some potential drug interactions that can occur with Duloxetine are as follows (1,2,3):

CYP 450 inhibitors

The enzymes CYP1A2 and CYP2D6 are responsible for the metabolism of Duloxetine. Medications that inhibit these enzymes can cause delayed metabolism of Duloxetine and an increase in its effects. Too much Duloxetine can cause an increased risk of side effects which can increase the risk of side effects of Duloxetine.

For example, Fluvoxamine is the inhibitor of the CYP1A2 enzyme and an antidepressant itself. If coadministered with Duloxetine it can cause a potentially fatal side effect known as the serotonin syndrome. Fluvoxamine also has a very mild inhibitory effect on the CYP2D6 enzyme.

NSAIDs and Antiplatelet medications

Anticoagulant medications like aspirin and warfarin can interact with Duloxetine. Duloxetine inhibits the reuptake of serotonin. Serotonin is responsible for the effects of platelet aggregation. When used concomitantly with NSAIDs, aspirin or warfarin, Duloxetine may increase the risk of bleeding. Many cases have been reported with increased upper gastrointestinal (GI) bleeding. 

Benzodiazepines and Tricyclic antidepressants (TCAs)

The benzodiazepines are known to cause sedation as a side effect. The same side effect has been experienced by individuals using Duloxetine. If both these medications are coadministered excessive sedation can occur, which may be harmful for the individual.

Medication like desipramine should not be administered with Duloxetine because it inhibits the enzymes responsible for the metabolism of desipramine. This can enhance the beneficial effects and side effects of Desipramine.

Serotonergic drugs and Monoamine oxidase inhibitors (MAOIs)

Serotonergic drugs when used with Duloxetine, may enhance the activity of serotonin which can lead to serotonin toxicity in individuals taking the medication. This phenomenon is termed the serotonin syndrome. The coadministration of  SSRIs or other SNRIs with Duloxetine can cause this side effect.

Monoamine oxidase inhibitors (MAOIs) also cause serotonin syndrome if taken simultaneously with Duloxetine. The FDA has warned to use both medications with a break of almost two weeks.

Triptans and Anticonvulsants

Serotonin syndrome can occur when Triptans are used with Duloxetine. Cases of the same have also been reported. If the simultaneous use of both medications is necessary, constant monitoring should be done to check for the occurrence of serotonin syndrome.

Lamotrigine is an anticonvulsant/antiepilepsy medication which tends to interact with Duloxetine. If used simultaneously there is an increased risk of serotonin syndrome, hyponatremia, seizures and cognitive impairment.

Alcohol

Alcohol and Duloxetine should not be used together. Alcohol tends to increase the side effects of Duloxetine. There is also an increased risk of hepatotoxicity and liver failure if alcohol and Duloxetine are used simultaneously for a long duration. To avoid this interaction, people who are heavy drinkers should not be prescribed Duloxetine.

Keep in mind that each individual has a unique physiology. Different individuals may react differently to Duloxetine and the simultaneous use of any other medication. Sometimes medications that do not normally interact with Duloxetine may interact in a special case. 

It is advised to consult your healthcare provider before starting or stopping any medication, while also taking Duloxetine.

What measures can be taken to minimize drug interactions with Duloxetine?

There are a few things that can be done to minimize or prevent drug interactions while taking Duloxetine. Some of them are as follows:

  • Avoid combining medications that can cause interactions when used with Duloxetine.
  • If the other medication is more necessary, discontinue Duloxetine and give an alternative antidepressant where possible.
  • If both medications are mandatory, they should be used cautiously and with constant monitoring. 
  • You should record any symptoms that you experience and communicate them to your healthcare provider.
  • You should not miss any follow-up appointments, because they are a chance for your doctor to assess any side effects of the combination.
  • If you experience uncomfortable symptoms that do not go away, you should immediately seek medical assistance.

To the best of my knowledge and according to published safety data Duloxetine can interact with many medications and cause an array of side effects. It is advised to avoid any such combination that can cause serious or fatal interaction with Duloxetine.

However, your healthcare provider may prescribe you such combinations if the benefits outweigh the risks and there is not much chance of a fatal interaction. Constant monitoring is advised in this case and if any severe side effect occurs then the combination should be discontinued.

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References

1.-

The Food and Drug Administration (FDA). HIGHLIGHTS OF PRESCRIBING INFORMATION. CYMBALTA® (duloxetine hydrochloride) Delayed released capsules for oral use. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022516lbl.pdf 

2.-

Knadler MP, Lobo E, Chappell J, Bergstrom R. Duloxetine: clinical pharmacokinetics and drug interactions. Clinical pharmacokinetics. 2011 May;50:281-94. https://link.springer.com/article/10.2165/11539240-000000000-00000

3.-

Lobo ED, Bergstrom RF, Reddy S, Quinlan T, Chappell J, Hong Q, Ring B, Knadler MP. In vitro and in vivo evaluations of cytochrome P450 1A2 interactions with duloxetine. Clinical pharmacokinetics. 2008 Mar;47:191-202. https://link.springer.com/article/10.2165/00003088-200847030-00005

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