Fluoxetine with Cilostazol Interaction Details

Brand Names Associated with Fluoxetine

Brand Names Associated with Cilostazol

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

Interaction Effect

Increased cilostazol exposure and an increased risk of bleeding

Interaction Summary

Cilostazol (a CYP2C19 substrate) exposure is increased with concomitant administration of FLUoxetine (a CYP2C19 inhibitor). Concomitant use of cilostazol (a CYP2C19 substrate) and omeprazole (a CYP2C19 inhibitor) resulted in increased plasma concentrations of cilostazol and one of its active metabolites . Additionally, case-control and cohort studies have shown that coadministration of SSRIs and antiplatelet agents has been associated with an increased risk of bleeding due to the additive effects on platelets. Bleeding events reported have included epistaxis, ecchymosis, hematoma, petechiae, and life-threatening hemorrhages . If coadministration is required, consider reducing the cilostazol dose to 50 mg twice daily  and monitor patient for signs of increased bleeding .

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Cilostazol (a CYP2C19 substrate) exposure is increased with concomitant administration of FLUoxetine (a CYP2C19 inhibitor). Additionally, concomitant use of SSRIs and antiplatelet agents may increase the risk of bleeding due to the additive effects on platelets . If coadministration is required, consider reducing the cilostazol dose to 50 mg twice daily  and monitor patient for signs of increased bleeding .

Mechanism Of Interaction

Inhibition of CYP2C19-mediated metabolism of cilostazol; release of serotonin by platelets; additive effects on hemostasis

Literature Reports

A) Concomitant use of cilostazol, a CYP2C19 substrate, and omeprazole, a CYP2C19 inhibitor, resulted in increased plasma concentrations of cilostazol and one of its active metabolites. Twenty healthy nonsmoking volunteers participated in a single-center, open-label study to evaluate the effect of omeprazole on the pharmacokinetics of a single dose of cilostazol 100 mg. Each study subject received cilostazol 100 mg on day 0 under fasting conditions. On days 7 through 18, omeprazole 40 mg was given each morning. Another single dose of cilostazol 100 mg was administered with omeprazole on day 14. After omeprazole administration, the Cmax of cilostazol increased by 18% (from 782 mcg/L to 921 mcg/L) and the AUC increased by 26% (from 10,287 mcg/L/h to 13,033 mcg/L/hr). The mean Cmax of OPC-13015, a pharmacologically active metabolite of cilostazol, increased by 29% and the AUC increased by 69% in the presence of omeprazole. Conversely, the Cmax and AUC of OPC-13213, another pharmacologically active metabolite of cilostazol, decreased by 22% and 31%, respectively. Although the changes in systemic exposure to cilostazol were well tolerated, the dose of cilostazol should be reduced to 50 mg twice daily when given concurrently with omeprazole .

B) Case reports and epidemiological studies (case-control and cohort studies) have demonstrated an association between the use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage. Bleeding events related to SSRIs and SNRIs have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages .

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.

Cilostazol Overview

• Cilostazol is used to reduce the symptoms of intermittent claudication (pain in the legs that worsens when walking and improves when resting that is caused by narrowing of the blood vessels that supply blood to the legs). Cilostazol is in a class of medications called platelet-aggregation inhibitors (antiplatelet medications). It works by improving blood flow to the legs.

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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.