Fluoxetine with Eliglustat Interaction Details

Brand Names Associated with Fluoxetine

Brand Names Associated with Eliglustat

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 11, 2023

Interaction Effect

Increased eliglustat exposure and subsequent prolongation of the QT interval

Interaction Summary

Coadministration with CYP2D6 inhibitors is predicted to increase eliglustat AUC 4.5-fold to 8.4-fold in extensive metabolizers, and 1.6-fold to 2.3-fold in intermediate metabolizers. In extensive and intermediate CYP2D6 metabolizers without hepatic impairment, reduce the eliglustat dose to 84 mg once daily when used concomitantly with a strong or moderate CYP2D6 inhibitor. In extensive metabolizers with mild hepatic impairment (Child-Pugh A), concomitant use with a strong or moderate CYP2D6 inhibitor is contraindicated. In extensive and intermediate metabolizers, the concomitant use of both a CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor with eliglustat is contraindicated. In poor metabolizers, concomitant use of eliglustat with both a CYP2D6 inhibitor and a strong CYP3A inhibitor is contraindicated, while concomitant use of both a CYP2D6 inhibitor with a moderate CYP3A inhibitor is to be avoided.

Severity

Contraindicated

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

In extensive and intermediate CYP2D6 metabolizers without hepatic impairment, reduce the eliglustat dose to 84 mg once daily when used concomitantly with a strong or moderate CYP2D6 inhibitor. In extensive metabolizers with mild hepatic impairment (Child-Pugh A), concomitant use with a strong or moderate CYP2D6 inhibitor is contraindicated. In extensive and intermediate metabolizers, the concomitant use of both a CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor with eliglustat is contraindicated. In poor metabolizers, concomitant use of eliglustat with both a CYP2D6 inhibitor and a strong CYP3A inhibitor is contraindicated, while concomitant use of both a CYP2D6 inhibitor with a moderate CYP3A inhibitor is to be avoided.

Mechanism Of Interaction

Inhibition of CYP2D6-mediated eliglustat metabolism

Literature Reports

A) Coadministration of eliglustat 84 mg twice daily with the strong CYP2D6 inhibitor paroxetine (30 mg/day) led to 7-fold and 8.4-fold increases in eliglustat Cmax and AUC, respectively, in extensive CYP2D6 metabolizers with Gaucher disease type 1 (N=30). Intermediate CYP2D6 metabolizers were predicted to experience 2.1- and 2.3-fold increases in eliglustat Cmax and AUC, respectively. Among extensive CYP2D6 metabolizers treated with eliglustat and terbinafine, simulations suggested that coadministration would cause eliglustat Cmax and AUC to rise 3.8-fold and 4.5-fold, respectively, and to increase 1.6-fold in intermediate CYP2D6 metabolizers 

B) Among extensive CYP2D6 metabolizers with Gaucher disease type 1, simulations suggested that eliglustat Cmax would increase 16.7-fold and AUC would increase 24.2-fold with concomitant use of ketoconazole (a strong CYP3A inhibitor) plus paroxetine (a strong CYP2D6 inhibitor). Among intermediate metabolizers, the predicted eliglustat Cmax would increase 7.5-fold and AUC would increase 9.8-fold with concurrent use of ketoconazole plus paroxetine. Among extensive CYP2D6 metabolizers with Gaucher disease type 1, simulations suggested that eliglustat Cmax would increase 10.2-fold and AUC would increase 13.6-fold with concomitant use of fluconazole (a moderate CYP3A inhibitor) plus terbinafine (a strong CYP2D6 inhibitor). Among intermediate CYP2D6 metabolizers, the predicted eliglustat Cmax and AUC was 4.2- and 5-fold higher, respectively, with concurrent use of fluconazole plus terbinafine .

Fluoxetine Overview

• Fluoxetine is used to treat depression, obsessive-compulsive disorder (bothersome thoughts that won't go away and the need to perform certain actions over and over), some eating disorders, and panic attacks (sudden, unexpected attacks of extreme fear and worry about these attacks). Fluoxetine is also used to relieve the symptoms of premenstrual dysphoric disorder, including mood swings, irritability, bloating, and breast tenderness. It is also used along with olanzapine (Zyprexa) to treat depression that did not respond to other medications and episodes of depression in people with bipolar I disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Fluoxetine is in a class of medications called selective serotonin reuptake inhibitors (SSRIs). It works by increasing the amount of serotonin, a natural substance in the brain that helps maintain mental balance.

Eliglustat Overview

• Eliglustat is used to treat Gaucher disease type 1 (a condition in which a certain fatty substance is not broken down normally in the body and builds up in some organs and causes liver, spleen, bone, and blood problems) in certain people. Eliglustat is in a class of medications called enzyme inhibitors. It works by preventing the body from producing the fatty substance so that less of it will build up in the body and cause symptoms.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.