Background: Interaction between proton pump inhibitors (PPI) and warfarin is controversial. Previous clinical studies have only a short follow-up period. Methods and Results: All patients (n = 716) for whom warfarin w...Background: Interaction between proton pump inhibitors (PPI) and warfarin is controversial. Previous clinical studies have only a short follow-up period. Methods and Results: All patients (n = 716) for whom warfarin was prescribed from November 1, 2010 to October 30, 2011 were extracted from electronic health records. In retrospective analysis for 1 year, PPI were prescribed to 404 patients. Among them, 108 patients were taking warfarin for more than 6 weeks before and after PPI. The profile of these patients was analyzed: 63 patients took lansoprazole;15 patients took omeprazole;30 patients took rabeprazole. No statistical difference was observed among 3 groups in age, body weight, concomitant use of other drugs, and comorbidity. Warfarin dose and INR did not change after PPI. Multivariate stepwise logistic regression analysis revealed that upper quartile of increment of INR was associated with the presence of atrial fibrillation (OR 3.77, 95% CI 1.16 - 12.27). The patients who had warfarin for shorter periods before PPI, or those who had PPI first (n = 141) had similar dose of warfarin and INR. In all patients analyzed (n = 404), including patients whose follow-up periods were shorter than 6 weeks (n = 155), a patient had cerebral bleeding, and 2 patients had cerebral infarction. Conclusions: Unfavorable interaction between warfarin and PPI was negligible in clinical use. Relatively higher INR was achieved after PPI in the presence of atrial fibrillation.展开更多
Background: Proton pump inhibitors (PPIs) are drugs that reduce the production of acid in the stomach. Recently, the use of PPI has been increasing among communities, whether with or without prescription. As a part of...Background: Proton pump inhibitors (PPIs) are drugs that reduce the production of acid in the stomach. Recently, the use of PPI has been increasing among communities, whether with or without prescription. As a part of the healthcare team, the pharmacist should not only dispense medications but also ensure the appropriate use of these medications. Studies conducted within 16 countries showed substantial variation in the appropriateness of the use of PPI drugs. Aim: To evaluate the appropriateness of PPIs use in Sharjah, UAE based on surveys answered by pharmacists, physicians, and patients. Methods: A cross-sectional survey study was conducted on December 2017 at Sharjah, UAE as an example of information obtained from the Middle East. Two different surveys were conducted on physicians and pharmacists. Both Physicians and Pharmacists were chosen randomly from Yellow Pages. The results obtained from both studies were used to develop a patient’s survey, which was distributed among University of Sharjah students, their families and random people at Shopping Malls and Clinics. Results: The results obtained from the patients’ survey showed that ~39% of PPI users from the region of Sharjah are 25 - 44 years old. Approximately 79% are using PPI according to physicians’ prescriptions. Prescriptions’ duration is varied between 1 month (39%) and 6 months (22%), where 52% of PPI users ask their physicians to prescribe PPIs when needed. Suggested reasons for the use of PPI included inappropriate food habits (52%), use of other medications (16%) or bacterial infection (13%). Around 52% of the patients did not receive any recommendations regarding the deprescribing of PPIs. According to the pharmacists’ surveys, an average sale of 5 - 10 PPI packages is reported per day, and around 50% are sold without a prescription. Most pharmacists were not fully aware of the health conditions and side effects of PPI drugs. On the other hand, physicians’ surveys showed that PPIs were mainly prescribed in the case of GERD and ulcer and for a maximum of 2 - 4 weeks. Approximately 75% of physicians recommend changing regimen by reducing the dose and stopping in case of chronic use of PPIs. Conclusion: The results from this survey study indicated that even though most PPI consumers at Sharjah, UAE are well aware of the use of PPI drugs and they follow the instructions given by the Physicians’, there is some discrepancy in the information obtained by the physicians, pharmacists, and patients. The reason for this discrepancy may be attributed to the missing role of the pharmacists which is currently just dispensing the medications without appropriate counseling. Thus the appropriate role of the pharmacists should be implemented according to the known international guidelines.展开更多
Introduction: Proton pump inhibitors (PPi) are widely prescribed, including in patients undergoing treatment for advanced breast cancer (ABC). Due to the pharmacokinetic characteristics of the CDK4/6 inhibitor (Ci) pa...Introduction: Proton pump inhibitors (PPi) are widely prescribed, including in patients undergoing treatment for advanced breast cancer (ABC). Due to the pharmacokinetic characteristics of the CDK4/6 inhibitor (Ci) palbociclib a drug interaction with PPi was hypothesized. It was shown in a retrospective study that this association was an independent predictive factor for worse progression-free survival (PFS). Objective: To verify the impact of concomitant administration of PPi with Ci on overall survival (OS) and PFS. Material and Methods: This is a retrospective cohort study of patients treated with Ci for HR+HER2-ABC in the period from Feb/2017 to Aug/2020. SPSS software was used for data processing. Univariate analysis was done by the Kaplan-Meier method and log-rank test, and multivariate analysis by COX regression. P-value < 0.05 was considered significant. Results: 80 patients were included. The median age at diagnosis of ABC was 56 years (25 - 75). Treatment with Ci was 1st line for ABC in 68.8%. Choice of Ci was palbociclib in 73.8% (n = 59) and ribociclib in 26.3% (n = 21). The hormone partner was a nonsteroidal aromatase inhibitor in 45.0%, and fulvestrant in 55.0% of cases. 37.5% of patients were on PPi, and 70.0% of them were during the entire treatment (23.3% omeprazole, 73.4% pantoprazole, 3.3% others). Patients taking concomitant PPi and Ci had lower OS (OS-3 years 42.6% vs. 63.4%, p = 0.254) and PFS (PFS med 15 m. vs. 21 m., p = 0.733), although with no statistically significant difference. Discussion: In the sample, there was a numerical difference, without the statistical significance in the use of PPi in the survival of patients under Ci. This difference could be more evident with a longer follow-up and a larger sample size. This study intends to alert to the growing importance of checking for drug interactions. Polymedication, advanced age and the presence of several comorbidities are real problems in patients with ABC. Conclusion: Real-world data from this center demonstrate a negative, non-statistically significant impact of PPi treatment on survival outcomes, in patients treated with Ci for HR+HER2-ABC.展开更多
Clopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic events.Concomitant treatment with proton pump inhibitors in...Clopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic events.Concomitant treatment with proton pump inhibitors in order to prevent gastrointestinal side effects is recommended by clinical guidelines.Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme Cytochrome 2C19(CYP2C19) and proton pump inhibitors(PPIs) are extensively metabolized by the CYP2C19 isoenzyme as well.Several pharmacodynamic studies investigating a potential clopidogrel-PPI interaction found a significant decrease of the clopidogrel platelet antiaggregation effect for omeprazole,but not for pantoprazole.Initial clinical cohort studies in 2009 reported an increased risk for adverse cardiovascular events,when under clopidogrel and PPI treatment at the same time.These observations led the United States Food and Drug Administration and the European Medecines Agency to discourage the combination of clopidogrel and PPI(especially omeprazole) in the same year.In contrast,more recent retrospective cohort studies including propensity score matching and the only existing randomized trial have not shown any difference concerning adverse cardiovascular events when concomitantly on clopidogrel and PPI or only on clopidogrel.Three meta-analyses report an inverse correlation between clopidogrel-PPI interaction and study quality,with high and moderate quality studies not reporting any association,rising concern about unmeasured confounders biasing the low quality studies.Thus,no definite evidence exists for an effect on mortality.Because PPI induced risk reduction clearly overweighs the possible adverse cardiovascular risk in patients with high risk of gastrointestinal bleeding,combination of clopidogrel with the less CYP2C19 inhibiting pantoprazole should be recommended.展开更多
Background Proton pump inhibitors(PPIs) are recommended by the latest guidelines to reduce the risk of bleeding in acute myocardial infarction(AMI) patients treated with dual antiplatelet therapy(DAPT). However, previ...Background Proton pump inhibitors(PPIs) are recommended by the latest guidelines to reduce the risk of bleeding in acute myocardial infarction(AMI) patients treated with dual antiplatelet therapy(DAPT). However, previous pharmacodynamic and clinical studies have reported controversial results on the interaction between PPI and the P2 Y12 inhibitor clopidogrel. We investigated the impact of PPIs use on in-hospital outcomes in AMI patients, aiming to provide a new insight on the value of PPIs. Methods A total of 23,380 consecutive AMI patients who received clopidogrel with or without PPIs in the China Acute Myocardial Infarction(CAMI) registry were analyzed. The primary endpoint was major adverse cardiovascular and cerebrovascular events(MACCE) defined as a composite of in-hospital cardiac death, re-infarction and stroke. Propensity score matching(PSM) was used to control potential baseline confounders. Multivariate logistic regression analysis was performed to evaluate the effect of PPIs use on MACCE and gastrointestinal bleeding(GIB). Results Among the whole AMI population, a large majority received DAPT and 67.5% were co-medicated with PPIs. PPIs use was associated with a decreased risk of MACCE(Before PSM OR: 0.857, 95% CI: 0.742-0.990, P = 0.0359;after PSM OR: 0.862, 95% CI: 0.768-0.949, P = 0.0245) after multivariate adjustment. Patients receiving PPIs also had a lower risk of cardiac death but a higher risk of complicating with stroke. When GIB occurred, an alleviating trend of GIB severity was observed in PPIs group. Conclusions Our study is the first nation-wide large-scale study to show evidence on PPIs use in AMI patients treated with DAPT. We found that PPIs in combination with clopidogrel was associated with decreased risk for MACCE in AMI patients, and it might have a trend to mitigate GIB severity. Therefore, PPIs could become an available choice for AMI patients during hospitalization.展开更多
Proton pump inhibitors often are prescribed in combination with clopidogrel to decrease risk of gastrointestinal bleeding after acute coronary syndrome. Clopidogrel is a prodrug that has to be metabolized in the liver...Proton pump inhibitors often are prescribed in combination with clopidogrel to decrease risk of gastrointestinal bleeding after acute coronary syndrome. Clopidogrel is a prodrug that has to be metabolized in the liver to generate the active metabolite. Both medications are metabolized largely by the CYP2C19 enzyme;therefore, concerns exist that a drug-drug interaction during concomitant treatment with clopidogrel and a proton pump inhibitor may result in reduction of platelet inhibition. We have reviewed observational and randomized control studies that have evaluated the potential influence of proton pump inhibitors on the platelet inhibitory effect of clopidogrel, along with cardiovascular outcomes. We also have summarized regulatory and academic guidelines for treatment of patients in which concomitant therapy with clopidogrel and proton pump inhibitors may be indicated. Confounding issues, including differential effects of individual proton pump inhibitors on the pharmacodynamics of clopidogrel and variation in clopidogrel metabolism mediated by CYP2C19 gene polymorphisms, also are discussed.展开更多
文摘Background: Interaction between proton pump inhibitors (PPI) and warfarin is controversial. Previous clinical studies have only a short follow-up period. Methods and Results: All patients (n = 716) for whom warfarin was prescribed from November 1, 2010 to October 30, 2011 were extracted from electronic health records. In retrospective analysis for 1 year, PPI were prescribed to 404 patients. Among them, 108 patients were taking warfarin for more than 6 weeks before and after PPI. The profile of these patients was analyzed: 63 patients took lansoprazole;15 patients took omeprazole;30 patients took rabeprazole. No statistical difference was observed among 3 groups in age, body weight, concomitant use of other drugs, and comorbidity. Warfarin dose and INR did not change after PPI. Multivariate stepwise logistic regression analysis revealed that upper quartile of increment of INR was associated with the presence of atrial fibrillation (OR 3.77, 95% CI 1.16 - 12.27). The patients who had warfarin for shorter periods before PPI, or those who had PPI first (n = 141) had similar dose of warfarin and INR. In all patients analyzed (n = 404), including patients whose follow-up periods were shorter than 6 weeks (n = 155), a patient had cerebral bleeding, and 2 patients had cerebral infarction. Conclusions: Unfavorable interaction between warfarin and PPI was negligible in clinical use. Relatively higher INR was achieved after PPI in the presence of atrial fibrillation.
文摘Background: Proton pump inhibitors (PPIs) are drugs that reduce the production of acid in the stomach. Recently, the use of PPI has been increasing among communities, whether with or without prescription. As a part of the healthcare team, the pharmacist should not only dispense medications but also ensure the appropriate use of these medications. Studies conducted within 16 countries showed substantial variation in the appropriateness of the use of PPI drugs. Aim: To evaluate the appropriateness of PPIs use in Sharjah, UAE based on surveys answered by pharmacists, physicians, and patients. Methods: A cross-sectional survey study was conducted on December 2017 at Sharjah, UAE as an example of information obtained from the Middle East. Two different surveys were conducted on physicians and pharmacists. Both Physicians and Pharmacists were chosen randomly from Yellow Pages. The results obtained from both studies were used to develop a patient’s survey, which was distributed among University of Sharjah students, their families and random people at Shopping Malls and Clinics. Results: The results obtained from the patients’ survey showed that ~39% of PPI users from the region of Sharjah are 25 - 44 years old. Approximately 79% are using PPI according to physicians’ prescriptions. Prescriptions’ duration is varied between 1 month (39%) and 6 months (22%), where 52% of PPI users ask their physicians to prescribe PPIs when needed. Suggested reasons for the use of PPI included inappropriate food habits (52%), use of other medications (16%) or bacterial infection (13%). Around 52% of the patients did not receive any recommendations regarding the deprescribing of PPIs. According to the pharmacists’ surveys, an average sale of 5 - 10 PPI packages is reported per day, and around 50% are sold without a prescription. Most pharmacists were not fully aware of the health conditions and side effects of PPI drugs. On the other hand, physicians’ surveys showed that PPIs were mainly prescribed in the case of GERD and ulcer and for a maximum of 2 - 4 weeks. Approximately 75% of physicians recommend changing regimen by reducing the dose and stopping in case of chronic use of PPIs. Conclusion: The results from this survey study indicated that even though most PPI consumers at Sharjah, UAE are well aware of the use of PPI drugs and they follow the instructions given by the Physicians’, there is some discrepancy in the information obtained by the physicians, pharmacists, and patients. The reason for this discrepancy may be attributed to the missing role of the pharmacists which is currently just dispensing the medications without appropriate counseling. Thus the appropriate role of the pharmacists should be implemented according to the known international guidelines.
文摘Introduction: Proton pump inhibitors (PPi) are widely prescribed, including in patients undergoing treatment for advanced breast cancer (ABC). Due to the pharmacokinetic characteristics of the CDK4/6 inhibitor (Ci) palbociclib a drug interaction with PPi was hypothesized. It was shown in a retrospective study that this association was an independent predictive factor for worse progression-free survival (PFS). Objective: To verify the impact of concomitant administration of PPi with Ci on overall survival (OS) and PFS. Material and Methods: This is a retrospective cohort study of patients treated with Ci for HR+HER2-ABC in the period from Feb/2017 to Aug/2020. SPSS software was used for data processing. Univariate analysis was done by the Kaplan-Meier method and log-rank test, and multivariate analysis by COX regression. P-value < 0.05 was considered significant. Results: 80 patients were included. The median age at diagnosis of ABC was 56 years (25 - 75). Treatment with Ci was 1st line for ABC in 68.8%. Choice of Ci was palbociclib in 73.8% (n = 59) and ribociclib in 26.3% (n = 21). The hormone partner was a nonsteroidal aromatase inhibitor in 45.0%, and fulvestrant in 55.0% of cases. 37.5% of patients were on PPi, and 70.0% of them were during the entire treatment (23.3% omeprazole, 73.4% pantoprazole, 3.3% others). Patients taking concomitant PPi and Ci had lower OS (OS-3 years 42.6% vs. 63.4%, p = 0.254) and PFS (PFS med 15 m. vs. 21 m., p = 0.733), although with no statistically significant difference. Discussion: In the sample, there was a numerical difference, without the statistical significance in the use of PPi in the survival of patients under Ci. This difference could be more evident with a longer follow-up and a larger sample size. This study intends to alert to the growing importance of checking for drug interactions. Polymedication, advanced age and the presence of several comorbidities are real problems in patients with ABC. Conclusion: Real-world data from this center demonstrate a negative, non-statistically significant impact of PPi treatment on survival outcomes, in patients treated with Ci for HR+HER2-ABC.
文摘Clopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic events.Concomitant treatment with proton pump inhibitors in order to prevent gastrointestinal side effects is recommended by clinical guidelines.Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme Cytochrome 2C19(CYP2C19) and proton pump inhibitors(PPIs) are extensively metabolized by the CYP2C19 isoenzyme as well.Several pharmacodynamic studies investigating a potential clopidogrel-PPI interaction found a significant decrease of the clopidogrel platelet antiaggregation effect for omeprazole,but not for pantoprazole.Initial clinical cohort studies in 2009 reported an increased risk for adverse cardiovascular events,when under clopidogrel and PPI treatment at the same time.These observations led the United States Food and Drug Administration and the European Medecines Agency to discourage the combination of clopidogrel and PPI(especially omeprazole) in the same year.In contrast,more recent retrospective cohort studies including propensity score matching and the only existing randomized trial have not shown any difference concerning adverse cardiovascular events when concomitantly on clopidogrel and PPI or only on clopidogrel.Three meta-analyses report an inverse correlation between clopidogrel-PPI interaction and study quality,with high and moderate quality studies not reporting any association,rising concern about unmeasured confounders biasing the low quality studies.Thus,no definite evidence exists for an effect on mortality.Because PPI induced risk reduction clearly overweighs the possible adverse cardiovascular risk in patients with high risk of gastrointestinal bleeding,combination of clopidogrel with the less CYP2C19 inhibiting pantoprazole should be recommended.
基金supported by the CAMS Innovation Fund for Medical Sciences (CIFMS, 2016-I2M-1-009)Twelfth Five-Year Planning Project of the Scientific and Technological Department of China (2011BAI11B02)National Natural Science Foundation of China (No 81670415)。
文摘Background Proton pump inhibitors(PPIs) are recommended by the latest guidelines to reduce the risk of bleeding in acute myocardial infarction(AMI) patients treated with dual antiplatelet therapy(DAPT). However, previous pharmacodynamic and clinical studies have reported controversial results on the interaction between PPI and the P2 Y12 inhibitor clopidogrel. We investigated the impact of PPIs use on in-hospital outcomes in AMI patients, aiming to provide a new insight on the value of PPIs. Methods A total of 23,380 consecutive AMI patients who received clopidogrel with or without PPIs in the China Acute Myocardial Infarction(CAMI) registry were analyzed. The primary endpoint was major adverse cardiovascular and cerebrovascular events(MACCE) defined as a composite of in-hospital cardiac death, re-infarction and stroke. Propensity score matching(PSM) was used to control potential baseline confounders. Multivariate logistic regression analysis was performed to evaluate the effect of PPIs use on MACCE and gastrointestinal bleeding(GIB). Results Among the whole AMI population, a large majority received DAPT and 67.5% were co-medicated with PPIs. PPIs use was associated with a decreased risk of MACCE(Before PSM OR: 0.857, 95% CI: 0.742-0.990, P = 0.0359;after PSM OR: 0.862, 95% CI: 0.768-0.949, P = 0.0245) after multivariate adjustment. Patients receiving PPIs also had a lower risk of cardiac death but a higher risk of complicating with stroke. When GIB occurred, an alleviating trend of GIB severity was observed in PPIs group. Conclusions Our study is the first nation-wide large-scale study to show evidence on PPIs use in AMI patients treated with DAPT. We found that PPIs in combination with clopidogrel was associated with decreased risk for MACCE in AMI patients, and it might have a trend to mitigate GIB severity. Therefore, PPIs could become an available choice for AMI patients during hospitalization.
文摘Proton pump inhibitors often are prescribed in combination with clopidogrel to decrease risk of gastrointestinal bleeding after acute coronary syndrome. Clopidogrel is a prodrug that has to be metabolized in the liver to generate the active metabolite. Both medications are metabolized largely by the CYP2C19 enzyme;therefore, concerns exist that a drug-drug interaction during concomitant treatment with clopidogrel and a proton pump inhibitor may result in reduction of platelet inhibition. We have reviewed observational and randomized control studies that have evaluated the potential influence of proton pump inhibitors on the platelet inhibitory effect of clopidogrel, along with cardiovascular outcomes. We also have summarized regulatory and academic guidelines for treatment of patients in which concomitant therapy with clopidogrel and proton pump inhibitors may be indicated. Confounding issues, including differential effects of individual proton pump inhibitors on the pharmacodynamics of clopidogrel and variation in clopidogrel metabolism mediated by CYP2C19 gene polymorphisms, also are discussed.
