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28 Μαρτίου 2024, 20:24:53

Αποστολέας Θέμα: Clopidogrel: Σε κάποιους δεν έχει αποτέλεσμα...  (Αναγνώστηκε 27337 φορές)

0 μέλη και 1 επισκέπτης διαβάζουν αυτό το θέμα.

23 Δεκεμβρίου 2008, 23:49:01
Αναγνώστηκε 27337 φορές
Αποσυνδεδεμένος

Δ. Κουναλάκης

Administrator
Cytochrome P-450 Polymorphisms and Response to Clopidogrel

ABSTRACT

Background Clopidogrel requires transformation into an active metabolite by cytochrome P-450 (CYP) enzymes for its antiplatelet effect. The genes encoding CYP enzymes are polymorphic, with common alleles conferring reduced function.

Methods We tested the association between functional genetic variants in CYP genes, plasma concentrations of active drug metabolite, and platelet inhibition in response to clopidogrel in 162 healthy subjects. We then examined the association between these genetic variants and cardiovascular outcomes in a separate cohort of 1477 subjects with acute coronary syndromes who were treated with clopidogrel in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction (TRITON–TIMI) 38.

Results In healthy subjects who were treated with clopidogrel, carriers of at least one CYP2C19 reduced-function allele (approximately 30% of the study population) had a relative reduction of 32.4% in plasma exposure to the active metabolite of clopidogrel, as compared with noncarriers (P<0.001). Carriers also had an absolute reduction in maximal platelet aggregation in response to clopidogrel that was 9 percentage points less than that seen in noncarriers (P<0.001). Among clopidogrel-treated subjects in TRITON–TIMI 38, carriers had a relative increase of 53% in the composite primary efficacy outcome of the risk of death from cardiovascular causes, myocardial infarction, or stroke, as compared with noncarriers (12.1% vs. 8.0%; hazard ratio for carriers, 1.53; 95% confidence interval [CI], 1.07 to 2.19; P=0.01) and an increase by a factor of 3 in the risk of stent thrombosis (2.6% vs. 0.8%; hazard ratio, 3.09; 95% CI, 1.19 to 8.00; P=0.02).

Conclusions Among persons treated with clopidogrel, carriers of a reduced-function CYP2C19 allele had significantly lower levels of the active metabolite of clopidogrel, diminished platelet inhibition, and a higher rate of major adverse cardiovascular events, including stent thrombosis, than did noncarriers.

source: Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος




Genetic Determinants of Response to Clopidogrel and Cardiovascular Events

ABSTRACT

Background Pharmacogenetic determinants of the response of patients to clopidogrel contribute to variability in the biologic antiplatelet activity of the drug. The effect of these determinants on clinical outcomes after an acute myocardial infarction is unknown.

Methods We consecutively enrolled 2208 patients presenting with an acute myocardial infarction in a nationwide French registry and receiving clopidogrel therapy. We then assessed the relation of allelic variants of genes modulating clopidogrel absorption (ABCB1), metabolic activation (CYP3A5 and CYP2C19), and biologic activity (P2RY12 and ITGB3) to the risk of death from any cause, nonfatal stroke, or myocardial infarction during 1 year of follow-up.

Results Death occurred in 225 patients, and nonfatal myocardial infarction or stroke in 94 patients, during the follow-up period. None of the selected single-nucleotide polymorphisms (SNPs) in CYP3A5, P2RY12, or ITGB3 were associated with a risk of an adverse outcome. Patients with two variant alleles of ABCB1 (TT at nucleotide 3435) had a higher rate of cardiovascular events at 1 year than those with the ABCB1 wild-type genotype (CC at nucleotide 3435) (15.5% vs. 10.7%; adjusted hazard ratio, 1.72; 95% confidence interval [CI], 1.20 to 2.47). Patients carrying any two CYP2C19 loss-of-function alleles (*2, *3, *4, or *5), had a higher event rate than patients with none (21.5% vs. 13.3%; adjusted hazard ratio, 1.98; 95% CI, 1.10 to 3.58). Among the 1535 patients who underwent percutaneous coronary intervention during hospitalization, the rate of cardiovascular events among patients with two CYP2C19 loss-of-function alleles was 3.58 times the rate among those with none (95% CI, 1.71 to 7.51).

Conclusions Among patients with an acute myocardial infarction who were receiving clopidogrel, those carrying CYP2C19 loss-of-function alleles had a higher rate of subsequent cardiovascular events than those who were not. This effect was particularly marked among the patients undergoing percutaneous coronary intervention. (ClinicalTrials.gov number, NCT00673036 [ClinicalTrials.gov] .)

source: Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος
Eίπες ότι μια μέρα θα φύγεις, μην τολμήσεις, είσαι χαζός;
όταν έχεις τέτοιους αυλικούς και τέτοια καρέκλα, τι απερισκεψία!
Ένα ξεροκόμματο κάθε πιστός να μασουλάει, "Ναι αρχηγέ" θα λέει συνεχώς
τιμωρία αμείλικτη σ' όποιον τολμά να σ΄αμφισβητεί έργα και πρόσωπα, τι ύβρης!
Ω αρχηγέ, είσαι ο μοναδικός, και τη ζωή μας χρωστάμε σε σένα οι φτωχοί!
Από μετάφραση αραβικού κειμένου

25 Απριλίου 2009, 23:44:43
Απάντηση #1
Αποσυνδεδεμένος

Δ. Κουναλάκης

Administrator
Dangerous Interaction Between Heartburn Drugs and Clopidogrel (PLAVIX)
Worst Pills Best Pills Newsletter article March, 2009

A new study, published online in Canadian Medical Association Journal January 28th, has found that people taking both clopidogrel (PLAVIX — a drug to prevent heart attacks in people who have just had a heart attack) and certain heartburn drugs, such as esomeprazole (NEXIUM — a PPI or proton pump inhibitor that inhibits stomach acid formation) had a 27 percent increased risk of subsequent heart attacks, compared with people who used only clopidogrel.

In the study, this dangerous interaction was only present in people who had used PPI drugs along with clopidogrel within the 30 days prior to their hospitalization with the recurrent heart attack. People who had used a PPI drug but stopped using it more than 30 days before the second heart attack did not have an increased risk of heart attacks compared to those who had never used PPI drugs with their clopidogrel.

The reason for this serious adverse interaction between these commonly used drugs is that clopidogrel is not effective until it has been converted to its active form by a drug-metabolizing enzyme in the liver. PPI drugs (such as esomeprazole) are often used by people who are taking clopidogrel because they are frequently taking aspirin as well and because clopidogrel can be irritating to the stomach.

When both drugs—clopidogrel and a PPI drug—are being used, the liver is stopped from converting clopidogrel into its active metabolic product. Much of the effectiveness of clopidogrel is therefore lost and its ability to prevent heart attacks is seriously impaired.

Recent guidelines published by the American Heart Association, the American College of Gastroenterology and the American College of Cardiology advocate proton pump inhibitor therapy for the majority of patients receiving ASA after myocardial infarction, including all patients aged 60 years or older. Our findings suggest that indiscriminate treatment with a proton pump inhibitor could result in thousands of additional cases of recurrent myocardial infarction each year, all of which could potentially be avoided by preferentially using pantoprazole in patients taking clopidogrel who require treatment with a proton pump inhibitor.

Of the two drugs involved in this interaction, clopidogrel is clearly the more important one in terms of its heart attack prevention effects.

We therefore agree with the FDA’s recommendation that "healthcare providers […] continue prescribing clopidogrel and […] re-evaluate the need for starting or continuing treatment with a PPI in clopidogrel recipients. Clopidogrel recipients are advised to consult their healthcare providers if they are receiving or considering taking a PPI."

Unlike the other PPI drugs, the Canadian study found no increase in repeat heart attacks in people using the PPI drug pantoprazole (PROTONIX) with clopidogrel.

This may be attributed to the fact that, unlike the other PPI drugs, pantoprazole does not inhibit the liver enzyme that converts clopidogrel into its active form. Thus, clopidogrel may be metabolized properly and the drug may prevent subsequent heart attacks.

Για τους μη αγγλομαθείς, μια πραζόλη σε έναν ασθενή που λαμβάνει Plavix-Iscover φροντίζει απλά να μην δρα το Plavix-Iscover του και εάν πραγματικά το χρειάζεται είναι σε κίνδυνο χωρίς να έχει τίποτα να κερδίσει από την πραζόλη σε σχέση με κάποιο άλλο φάρμακο πχ Ζαντακ.

Eίπες ότι μια μέρα θα φύγεις, μην τολμήσεις, είσαι χαζός;
όταν έχεις τέτοιους αυλικούς και τέτοια καρέκλα, τι απερισκεψία!
Ένα ξεροκόμματο κάθε πιστός να μασουλάει, "Ναι αρχηγέ" θα λέει συνεχώς
τιμωρία αμείλικτη σ' όποιον τολμά να σ΄αμφισβητεί έργα και πρόσωπα, τι ύβρης!
Ω αρχηγέ, είσαι ο μοναδικός, και τη ζωή μας χρωστάμε σε σένα οι φτωχοί!
Από μετάφραση αραβικού κειμένου

26 Απριλίου 2009, 00:10:26
Απάντηση #2
Αποσυνδεδεμένος

Gatekeeper

Επώνυμοι
Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος

Unlike the other PPI drugs, the Canadian study found no increase in repeat heart attacks in people using the PPI drug pantoprazole (PROTONIX) with clopidogrel.

This may be attributed to the fact that, unlike the other PPI drugs, pantoprazole does not inhibit the liver enzyme that converts clopidogrel into its active form. Thus, clopidogrel may be metabolized properly and the drug may prevent subsequent heart attacks.

Για τους μη αγγλομαθείς, μια πραζόλη σε έναν ασθενή που λαμβάνει Plavix-Iscover φροντίζει απλά να μην δρα το Plavix-Iscover του και εάν πραγματικά το χρειάζεται είναι σε κίνδυνο χωρίς να έχει τίποτα να κερδίσει από την πραζόλη σε σχέση με κάποιο άλλο φάρμακο πχ Ζαντακ.



ή CONTROLOC , ZURCAZOL κα Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος
“It’s a poor sort of memory that onlyworks backwards, the Queen remarked.”
Lewis Carroll, 1872,
Through the Looking Glass

10 Μαΐου 2009, 18:09:43
Απάντηση #3
Αποσυνδεδεμένος

Μαρία Χόρτη

Ιατροί
Προτείνεται η χρήση εναλλακτικών φαρμάκων των PPIs (πχ Zantac) σε ασθενείς υπο αντιθρομβωτική αγωγή

Providers Should Consider PPI Alternatives in Patients on Dual Antiplatelet Therapy, Group Advises

For patients receiving dual antiplatelet therapy who need heartburn treatment, healthcare providers should consider alternatives to proton pump inhibitors, the Society for Cardiovascular Angiography and Interventions (SCAI) has advised.
The group issued the recommendation after a large study showed adverse cardiac effects when clopodigrel was mixed with PPIs.
The study examined nearly 16,700 patients who took clopidogrel for a year after coronary stenting. Patients who were also using PPIs had significantly greater risk for the composite of MI, stroke, unstable angina, or repeat vascularization. Event rates ranged from 24% to 29% with lansoprazole (Prevacid), esomeprazole (Nexium), omeprazole (Prilosec), and pantoprazole (Protonix), compared with 18% without PPI use.
The SCAI calls for more research, but in the meantime, it advises providers to consider using histaminergic blockers (e.g., Zantac or Tagamet) or antacids instead of PPIs in this patient population.

SCAI statement
Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος

ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use
Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος

18 Μαΐου 2009, 09:21:01
Απάντηση #4
Αποσυνδεδεμένος

Δ. Κουναλάκης

Administrator
Οι υπάρχουσες μελέτες είναι αναδρομικές και στηρίζονται σε στατιστικά συμπεράσματα, τα σίγουρα θα τα έχουμε σε 2-3 χρόνια τουλάχιστον και το FDA δεν εξαίρεσε καμιά από τον πιθανό κίνδυνο. Επίσης, δεν εξαιρούν όλες οι μελέτες την παντοπραζόλη από αυτό το πρόβλημα. Υπάρχει πάντα η υποψία ότι επειδή είναι έτοιμος για κυκλοφορία ο "αντικαταστάτης" της κλοπιδογρέλης όλη η υπόθεση έχει στόχο να προετοιμάσει την επέλαση του.

Επειδή ζω τον αστερισμό των πραζολών όπου μετά την κυκλοφορία των φασόν ομεπραζόλης έχει γίνει το απίστευτο φαγοπότι θα έλεγα να σκεφτόμαστε διπλά το εάν μια πραζόλη είναι απαραίτητη στον ασθενή μας καθώς δεν είναι μόνο η κλοπιδογρέλη που έχει πρόβλημα αλλά και άλλες φαρμακευτικές ουσίες.

Επίσης, ίσως θα πρέπει να σκεφτούμε ξανά ότι εάν η πραζόλη είναι απαραίτητη ίσως ο συνδυασμός ασπιρίνη+πραζόλη είναι απίστευτα πιο προστατευτικός για τον ασθενή μας σε σχέση με κλοπιδογρέλη+πραζόλη, με καλύτερη λύση για κάποιες νοσολογικές οντότητες την κλοπιδογρέλη μόνη της χωρίς πραζόλη. Ας σκεφτούμε διπλά όταν δίνουμε ή συνεχίζουμε αγωγή σε κάποιον ασθενή μας.
Eίπες ότι μια μέρα θα φύγεις, μην τολμήσεις, είσαι χαζός;
όταν έχεις τέτοιους αυλικούς και τέτοια καρέκλα, τι απερισκεψία!
Ένα ξεροκόμματο κάθε πιστός να μασουλάει, "Ναι αρχηγέ" θα λέει συνεχώς
τιμωρία αμείλικτη σ' όποιον τολμά να σ΄αμφισβητεί έργα και πρόσωπα, τι ύβρης!
Ω αρχηγέ, είσαι ο μοναδικός, και τη ζωή μας χρωστάμε σε σένα οι φτωχοί!
Από μετάφραση αραβικού κειμένου

1 Ιουνίου 2009, 23:03:33
Απάντηση #5
Αποσυνδεδεμένος

Gatekeeper

Επώνυμοι
Possible "class effect" for proton-pump inhibitors on top of clopidogrel therapy

Las Vegas, NV - One-year risk of cardiovascular events is increased more than 50% in patients taking a proton-pump inhibitor (PPI) on top of clopidogrel, as compared with patients not taking a PPI, and the risk seems to be a class effect, according to a retrospective cohort study of more than 16 700 patients who received clopidogrel poststenting.

The study is the latest in an inconsistent series of reports trying to assess the clinical impact of combining the two classes of drugs. Professional society guidelines recommend the use of PPIs to treat and prevent gastrointestinal ulcers and bleeding in patients on antiplatelet therapy, but increasing use of PPIs in this setting has raised questions as to whether PPIs may attenuate clopidogrel's antiplatelet response by interfering with CYP2C19-mediated clopidogrel metabolism.

Dr Erick J Stanek (Medco Health Solutions, Franklin Lakes, NJ) presented the results of the Clopidogrel Medco Outcomes study as a late-breaking clinical trial during the first day of the Society for Cardiovascular Angiography and Interventions (SCAI) 2009 Scientific Sessions. The study compared major adverse cardiovascular events (MACE) among members of the Medco Health Solutions pharmacy and medical claims database. In all, 9862 patients never made a prescription claim for a PPI over the 12 months post-PCI and were classified as no PPI therapy for the purposes of the study, while 6828 filed prescription claims for a PPI: esomeprazole (Nexium, AstraZeneca), omeprazole, pantoprazole (Protonix, Wyeth), lansoprazole, or rabeprazole (Aciphex, Eisai/Ortho-McNeil-Janssen Pharmaceuticals).

Prescription status was then correlated with hospitalization for stroke/TIA, ACS, cardiovascular death, or coronary revascularization, based on ICD-9 or CPT-4 codes.

Higher MACE with PPIs
 
As Stanek showed here, one-year risk of MACE was significantly higher in PPI-treated subjects, at 25.1%, as compared with patients who did not take a PPI, at 17.9% (hazard ratio 1.51 [95% CI 1.39-1.64]; p<0.0001). According to investigators, PPI effect was "consistent across subgroups," with no single patient subset being significantly more likely to develop an adverse cardiovascular event.

They also looked at the CV risk associated with individual PPIs, restricting their analysis to PPIs with sufficient patient numbers to detect a difference in risk similar to that seen in the overall population, with adequate statistical power. Due to low numbers, rabeprazole, taken by just 298 patients, could not be addressed in this analysis.

According to Stanek, each of the PPIs, individually, was associated with a higher risk of major cardiovascular events vs no PPI use, ranging from a 24.3% increased risk with lansoprazole to a 29.2% risk with pantoprazole.

"There was considerable overlap between agents, suggesting this is somewhat a class effect," Stanek commented.

Of note, hospitalization rates for upper-GI bleeding were low across all groups of PPI use, in the range of 1.1%. Also of interest, investigators looked at PPI use among patients who were not treated with clopidogrel and found no increased risk of CV events in this group, as compared with patients taking neither a PPI nor clopidogrel.

"These results provide further support for the hypothesis that PPIs attenuate the effects of clopidogrel," Stanek concluded. "More data are needed to establish if newer PPIs . . . have similar effects. Considering all available evidence, PPI use should be limited to situations clearly indicated in patients on clopidogrel after coronary stenting."

Following Stanek's presentation and during a morning press conference, Dr Steven Bailey (University of Texas Health Sciences Center, San Antonio) confirmed with Stanek that the nature of the Medco analysis made it impossible to take into account whether patients were taking nonprescription medications, including aspirin as well as over-the-counter PPIs or other gastrointestinal agents, information that Bailey emphasized to be vitally important.

Bailey also emphasized that physicians need to do a better job of discriminating between patients who are just at risk of GI symptoms or who may have had previous GI disease and patients who actually have current GI problems—it is the latter group in whom concomitant PIs are likely to be useful, he said.

Stanek and colleagues are continuing to look at their data set, hoping to determine whether there are any signals of increased risk based on timing or duration of drug overlap. But Stanek hinted that based on information he's seen so far, "any length of exposure seems to be a problem."

Both Stanek and Bailey stressed, however, that the study was retrospective and "hypothesis-generating."

As Bailey put it: "This is not a cause for concern or alarm, but a cause for consultation." He urged physicians to take the time to discuss the risks and benefits with patients and also to emphasize that patients should not, by any means, stop clopidogrel therapy—a point also hammered by Stanek

More questions needing answers

 Asked to comment on the study for heartwire, Dr Peter Berger (Geisinger Health, Danville, PA) observed that it is impossible to know from a retrospective cohort study the full reasons for why patients are put on PPIs in the first place and whether these factors were key to their subsequent cardiovascular events. "In this study, as in nearly all others, patients on PPIs are older and sicker than patients who are not. All statistical methods are imperfect at adjusting for differences when the groups are so different, as they are in this analysis."

Berger pointed out that there are other reasons to question whether PPIs truly adversely affect clopidogrel efficacy. In the TRITON study, he notes, the reduction in cardiovascular risk seen with prasugrel over clopidogrel was identical in patients on and not on PPIs.

"Since PPIs are not believed to influence the efficacy of prasugrel, that suggests that clopidogrel was equally effective in both groups," he said. "And paradoxically, in TRITON, patients on clopidogrel and a PPI bled even more than patients on clopidogrel and not on a PPI; in fact, they bled almost as much as patients treated with prasugrel. If the clopidogrel wasn't working because the PPI prevented clopidogrel prodrug from being metabolized to its active compound, patients on both shouldn't have bled so much more."

SCAI issues statement urging caution with PPIs

SCAI believes more research is needed on this topic. However, given the thousands of patients who receive stents each year, coupled with the significant risks demonstrated in this study, SCAI recommends the use of alternative medications for GI symptoms in patients with stents when appropriate.  Other effective treatments for heartburn and ulcers include histaminergic (H2) blockers (Zantac [ranitidine, Boehringer Ingelheim], Tagamet [cimetidine, GlaxoSmithKline]) or antacids.  In some patients the use of PPIs may still be warranted, based on the patient's medical problems, and should be taken at the direction of the patient's cardiologist, gastroenterologist, or primary physician."



“It’s a poor sort of memory that onlyworks backwards, the Queen remarked.”
Lewis Carroll, 1872,
Through the Looking Glass

15 Ιουλίου 2009, 12:23:26
Απάντηση #6
Αποσυνδεδεμένος

Raptor

Ιατροί
Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος
Οι υπάρχουσες μελέτες είναι αναδρομικές και στηρίζονται σε στατιστικά συμπεράσματα, τα σίγουρα θα τα έχουμε σε 2-3 χρόνια τουλάχιστον και το FDA δεν εξαίρεσε καμιά από τον πιθανό κίνδυνο. Επίσης, δεν εξαιρούν όλες οι μελέτες την παντοπραζόλη από αυτό το πρόβλημα. Υπάρχει πάντα η υποψία ότι επειδή είναι έτοιμος για κυκλοφορία ο "αντικαταστάτης" της κλοπιδογρέλης όλη η υπόθεση έχει στόχο να προετοιμάσει την επέλαση του.


Effient (prasugrel)

Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος

Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος
"Success is getting what you want" "Happiness is wanting what you get"
"The secret of happiness is not found in seeking more, but in the capacity to enjoy less."

20 Οκτωβρίου 2009, 13:20:25
Απάντηση #7
Αποσυνδεδεμένος

Argirios Argiriou

Moderator
N Engl J Med. 2005 Jan 20;352(3):238-44

Chan FK, Ching JY, Hung LC, Wong VW, Leung VK, Kung NN, Hui AJ, Wu JC, Leung WK, Lee VW, Lee KK, Lee YT, Lau JY, To KF, Chan HL, Chung SC, Sung JJ.
Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong, China. fklchan@cuhk.edu.hk


BACKGROUND: Concurrent therapy with a proton-pump inhibitor is a standard treatment for patients receiving aspirin who are at risk for ulcer. Current U.S. guidelines also recommend clopidrogel for patients who have major gastrointestinal intolerance of aspirin. We compared clopidogrel with aspirin plus esomeprazole for the prevention of recurrent bleeding from ulcers in high-risk patients. METHODS: We studied patients who took aspirin to prevent vascular diseases and who presented with ulcer bleeding. After the ulcers had healed, we randomly assigned patients who were negative for Helicobacter pylori to receive either 75 mg of clopidogrel daily plus esomeprazole placebo twice daily or 80 mg of aspirin daily plus 20 mg of esomeprazole twice daily for 12 months. The end point was recurrent ulcer bleeding. RESULTS: We enrolled 320 patients (161 patients assigned to receive clopidogrel and 159 to receive aspirin plus esomeprazole). Recurrent ulcer bleeding occurred in 13 patients receiving clopidogrel and 1 receiving aspirin plus esomeprazole. The cumulative incidence of recurrent bleeding during the 12-month period was 8.6 percent (95 percent confidence interval, 4.1 to 13.1 percent) among patients who received clopidogrel and 0.7 percent (95 percent confidence interval, 0 to 2.0 percent) among those who received aspirin plus esomeprazole (difference, 7.9 percentage points; 95 percent confidence interval for the difference, 3.4 to 12.4; P=0.001). CONCLUSIONS: Among patients with a history of aspirin-induced ulcer bleeding whose ulcers had healed before they received the study treatment, aspirin plus esomeprazole was superior to clopidogrel in the prevention of recurrent ulcer bleeding. Our finding does not support the current recommendation that patients with major gastrointestinal intolerance of aspirin be given clopidogrel.

Copyright 2005 Massachusetts Medical Society.

PMID: 15659723 [PubMed - indexed for MEDLINE]



Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος
Before ordering a test decide what you will do if it is (1) positive, or (2) negative. If both answers are the same, don't do the test. Archie Cochrane.

18 Νοεμβρίου 2009, 14:59:37
Απάντηση #8
Αποσυνδεδεμένος

Raptor

Ιατροί
Information for Healthcare Professionals: Update to the labeling of Clopidogrel Bisulfate (marketed as Plavix) to alert healthcare professionals about a drug interaction with omeprazole (marketed as Prilosec and Prilosec OTC)
[11/17/2009]

FDA is alerting the public to new safety information concerning an interaction between clopidogrel (Plavix), an anti-clotting medication, and omeprazole (Prilosec/Prilosec OTC), a proton pump inhibitor (PPI) used to reduce stomach acid. New data show that when clopidogrel and omeprazole are taken together, the effectiveness of clopidogrel is reduced. Patients at risk for heart attacks or strokes who use clopidogrel to prevent blood clots will not get the full effect of this medicine if they are also taking omeprazole. The updated label for clopidogrel will contain details of new studies submitted by Sanofi-Aventis and Bristol-Myers Squibb, the manufacturer of Plavix (clopidogrel).

Omeprazole inhibits the drug metabolizing enzyme (CYP2C19) which is responsible for the conversion of clopidogrel into its active form (active metabolite). The new studies compared the amount of clopidogrel's active metabolite in the blood and its effect on platelets (anti-clotting effect) in people who took clopidogrel plus omeprazole versus those who took clopidogrel alone. A reduction in active metabolite levels of about 45% was found in people who received clopidogrel with omeprazole compared to those taking clopidogrel alone. The effect of clopidogrel on platelets was reduced by as much as 47% in people receiving clopidogrel and omeprazole together. These reductions were seen whether the drugs were given at the same time or 12 hours apart.

Other drugs that are potent inhibitors of the CYP 2C19 enzyme would be expected to have a similar effect and should be avoided in combination with clopidogrel. These include: cimetidine, fluconazole, ketoconazole, voriconazole, etravirine, felbamate, fluoxetine, fluvoxamine, and ticlopidine. Since the level of inhibition among other PPIs varies, it is unknown to what amount other PPIs may interfere with clopidogrel. However, esomeprazole, a PPI that is a component of omeprazole, inhibits CYP2C19 and should also be avoided in combination with clopidogrel.

FDA is aware there are studies, such as the Clopidogrel and Optimization of Gastrointestinal Events (COGENT) study, that might provide information about the effect of this interaction on clinical outcome. Although the FDA has not fully reviewed the study results, the applicability of these data is limited because of the study design and follow-up. Therefore, based on the current scientific information, the clopidogrel label has been updated with new warnings on omeprazole and other drugs that inhibit the CYP2C19 enzyme that could interact with clopidogrel in the same way. In addition, the manufacturer of Plavix (clopidogrel) is conducting follow-up studies to explore this and other drug interactions.

Considerations for Healthcare Professionals

The concomitant use of omeprazole and clopidogrel should be avoided because of the effect on clopidogrel's active metabolite levels and anti-clotting activity. Patients at risk for heart attacks or strokes, who are given clopidogrel to prevent blood clots, may not get the full protective anti-clotting effect if they also take prescription omeprazole or the OTC form (Prilosec OTC).
Separating the dose of clopidogrel and omeprazole in time will not reduce this drug interaction.

Other drugs that should be avoided in combination with clopidogrel because they may have a similar interaction include: esomeprazole (Nexium), cimetidine (which is available by prescription Tagamet and OTC as Tagamet HB), fluconazole (Diflucan), ketoconazole (Nizoral), voriconazole (VFEND), etravirine (Intelence), felbamate (Felbatol), fluoxetine (Prozac, Serafem, Symbyax), fluvoxamine (Luvox), and ticlopidine (Ticlid).

At this time FDA does not have sufficient information about drug interactions between clopidogrel and PPIs other than omeprazole and esomeprazole to make specific recommendations about their co-administration. Healthcare professionals and patients should consider all treatment options carefully before beginning therapy.

There is no evidence that other drugs that reduce stomach acid, such as most H2 blockers ranitidine (Zantac), famotidine (Pepcid), nizatidine (Axid), except cimetidine (Tagamet and Tagamet HB - a CYP2C19 inhibitor) or antacids interfere with the anti-clotting activity of clopidogrel. Ranitidine and famotidine are available by prescription and OTC to relieve and prevent heartburn and antacids are available OTC to relieve heartburn.

Talk with your patients about the OTC medicines they take. Be aware that patients may be taking non prescription forms omeprazole and cimetidine.

FDA will continue to investigate other drug interactions with clopidogrel. FDA plans on presenting this issue at the next meeting of FDA's Drug Safety Oversight Board in November. The Agency will communicate any further recommendations or conclusions once additional information is available.

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"Success is getting what you want" "Happiness is wanting what you get"
"The secret of happiness is not found in seeking more, but in the capacity to enjoy less."

21 Μαρτίου 2011, 23:06:46
Απάντηση #9
Αποσυνδεδεμένος

Argirios Argiriou

Moderator
Nat Med. 2011 Jan;17(1):110-6. Epub 2010 Dec 19.

Paraoxonase-1 is a major determinant of clopidogrel efficacy.
Bouman HJ, Schömig E, van Werkum JW, Velder J, Hackeng CM, Hirschhäuser C, Waldmann C, Schmalz HG, ten Berg JM, Taubert D.

Department of Cardiology, St. Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands.

Comment in:

Nat Rev Drug Discov. 2011 Feb;10(2):100.
Nat Med. 2011 Jan;17(1):40-1.

Abstract
Clinical efficacy of the antiplatelet drug clopidogrel is hampered by its variable biotransformation into the active metabolite. The variability in the clinical response to clopidogrel treatment has been attributed to genetic factors, but the specific genes and mechanisms underlying clopidogrel bioactivation remain unclear. Using in vitro metabolomic profiling techniques, we identified paraoxonase-1 (PON1) as the crucial enzyme for clopidogrel bioactivation, with its common Q192R polymorphism determining the rate of active metabolite formation. We tested the clinical relevance of the PON1 Q192R genotype in a population of individuals with coronary artery disease who underwent stent implantation and received clopidogrel therapy. PON1 QQ192 homozygous individuals showed a considerably higher risk than RR192 homozygous individuals of stent thrombosis, lower PON1 plasma activity, lower plasma concentrations of active metabolite and lower platelet inhibition. Thus, we identified PON1 as a key factor for the bioactivation and clinical activity of clopidogrel. These findings have therapeutic implications and may be exploited to prospectively assess the clinical efficacy of clopidogrel.


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Before ordering a test decide what you will do if it is (1) positive, or (2) negative. If both answers are the same, don't do the test. Archie Cochrane.

22 Μαρτίου 2011, 16:22:58
Απάντηση #10
Αποσυνδεδεμένος

Nikos_med


Παρεπιπτόντως για την κλοπιδογρέλη, τελικώς, εάν είναι-και καλά απαραίτητο ένα ppi, ποιο συνταγογραφούμε, αποκλειστικά παντοπραζόλη ή μπορούμε και εσομπεραζόλη; Μόνο διφορούμενα στοιχεία βρίσκουμε στην ώς τώρα αρθρογραφία. Σήμερα, επανέλαβα συνταγή Iscover με Nexium από ιατρό ειδικότητας ογκολογίας, συνταγή προ μηνός, με διάγνωση βέβαια φλεβοθρόμβωση Ca επιπλοκή και ΓΟΠ, συνταγή χρόνιου ελέγχου και όχι με πρόσφατη χορήγηση αντι-νεο φαρμάκου. Έπραξα σωστά; Η επικοινωνία μαζί του ήταν αδύνατη, ενώ στο νετ δεν βρήκα κάτι ιδιαίτερο (να 'ναι καλά το iphone), ενώ κατά το παρελθόν ένας καρδιολόγος έχει πει, βάσει άρθρου ότι δεν αλληλεπιδρούν, ενώ ένας άλλος, βάσει άλλου άρθρου, ότι αλληλεπιδρούν, προτιμάμε παντοπραζόλη που μάλιστα δεν χρειάζεται να ληφθεί με 12 ώρες διαφορά...Τα άρθρα βέβαια που παραθέτει ο κ. Κουναλάκης είναι κατά του Nexium, αλλά βλέπω ότι δεν ακολουθούν όλοι την ίδια γραμμή...Στο medscape interaction checker πάντως όλα τα ppis τίθενται στην ίδια μοίρα.

9 Φεβρουαρίου 2013, 16:03:25
Απάντηση #11
Αποσυνδεδεμένος

Argirios Argiriou

Moderator
Thrombosis Research (2007) 120, 311–321

REVIEW ARTICLE

Clopidogrel resistance?

Paul A. Gurbel, Udaya S. Tantry

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« Τελευταία τροποποίηση: 9 Φεβρουαρίου 2013, 16:07:48 από Argirios Argiriou »
Before ordering a test decide what you will do if it is (1) positive, or (2) negative. If both answers are the same, don't do the test. Archie Cochrane.

 

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