Impact of Citalopharm and Fluvoxamine on Platelet Response to Clopidogrel
Information source: Hadassah Medical Organization
Information obtained from ClinicalTrials.gov on December 08, 2011
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Drug Interactions Between Clopidogrel and Serotonin Reuptake Inhibitors
Intervention: fluvoxamine (Drug); citalopharm (Drug)
Phase: Phase 1
Status: Not yet recruiting
Sponsored by: Hadassah Medical Organization
Ronny Alcalai, MD, Email: email@example.com
Clopidogrel is a platelets inhibitor that is widely used particularly during and after acute
coronary events and coronary interventions. Several studies have shown that some patients
are resistant to clopidogrel. The resistance mechanism is not entirely clear, but at least
in part it is related to interactions between medications. Clopidogrel is a pro-drug
converted in vivo to its active metabolite by CYP2C19 and CYP3A in the liver. Consequently
drugs that inhibit the CYP2C19 can affect the production of the active metabolite and cause
"clopidogrel resistance". Therefore the FDA has recently published a "safety alert" which
recommends avoiding cross treatment with clopidogrel and drugs that are expected to inhibit
CYP2C19 (including omeprazole, fluvoxamine, cimetidine, fluconazole and others).
Nevertheless there no clear evidence in the literature for clinical relevance of such
Selective serotonin reuptake inhibitors (SSRIs) are group of antidepressant drugs that are
widely used for treatment of depression and anxiety. SSRIs are considered to be very safe
with favorable side effect profile, hence many patient after coronary events who suffers
from behavioral and emotional disturbances are treated with those drugs. However there are
several reports that SSRIs can inhibit platelet function and increase bleeding tendency
particularly in concomitant administration with aspirin. The proposed mechanism is blocking
of platelets serotonin reuptake that result in platelet dysfunction.
Fluvoxamine - is a member in the SSRI family and a potent inhibitor of the CYP2C19.
Theoretically fluvoxamine should have two conflicting effects on the response to
clopidogrel. Pharmacokinetically it is expected to decrease the clopidogrel responsiveness
due to inhibition of CYP2C19 and reduction in the production of the active metabolite. On
the other hand "pharmacodynamically" fluvoxamine may directly inhibit platelet aggregation
due its effect on serotonin reuptake, thus increasing the effect of clopidogrel. Other SSRIs
that do not interact with the CYP2C19 such as citalophram are expected to have only
pharmocodynamic effect on platelet aggregation.
Although both clopidogrel and SSRIs are widely used in the last decade and concomitant
treatment is quite common, no data is available about in influence of the interaction
between those drugs on platelet function and on clinical events. The net effect of
fluvoxamine and other SSRIs on platelet function in the presence of clopidogrel is not
The aim of the investigators study is to assess the effect of two SSRIs fluvoxamine and
citalophram on platelet aggregation and to test the effect of these drugs on the laboratory
response to clopidogrel, in healthy individuals.
Study design: randomized, double blinded, controlled crossover trial. Primary study end
point: Change in % platelet aggregation and VASP phosphorylation after treatment with
clopidogrel + fluvoxamine or clopidogrel + citalophram as compared to each drug alone.
Official title: Impact of Citalopharm and Fluvoxamine on Platelet Response to Clopidogrel, a Randomized, Double-blind, Crossover Trial
Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Primary outcome: Platelet reactivity in response to clopidogrel
Minimum age: 18 Years.
Maximum age: 60 Years.
- Healthy volunteers
- Bleeding tendency
- Hypersensitivity to study drugs
Locations and Contacts
Ronny Alcalai, MD, Email: firstname.lastname@example.orgAdditional Information
Starting date: September 2011
Last updated: July 17, 2011