The EU Committee for Medicinal Products for Human Use (CHMP) has recently considered the available evidence for an interaction between clopidogrel and proton pump inhibitors (PPIs). They concluded that PPIs reduce the effectiveness of clopidogrel in preventing the recurrence of adverse cardiac events such as heart attack and coronary artery restenosis (renarrowing of the artery wall despite past heart surgery).
Further information, including a series of questions and answers for patients, is provided below. The European Medicines Agency (external link) has also recently published information on this interaction.
Information and advice for healthcare professionals is also published in the July issue of Drug Safety Update on page 2.
Clopidogrel
Clopidogrel (brand name Plavix) is used to prevent atherothrombotic events (e.g. a heart attack or stroke) in patients who have previously had one of these life-threatening events, or in at-risk patients who have peripheral arterial disease (narrowing of the arteries, mainly in the legs). In combination with aspirin, it can also be used to prevent atherothrombotic events in patients with acute coronary syndrome (a serious disorder with various clinical signs that suggest the heart is receiving inadequate oxygen).
Clopidogrel (brand name Plavix) is used to prevent atherothrombotic events (e.g. a heart attack or stroke) in patients who have previously had one of these life-threatening events, or in at-risk patients who have peripheral arterial disease (narrowing of the arteries, mainly in the legs). In combination with aspirin, it can also be used to prevent atherothrombotic events in patients with acute coronary syndrome (a serious disorder with various clinical signs that suggest the heart is receiving inadequate oxygen).
PPIs
PPIs are used to treat the gastrointestinal disorders, oesophageal reflux disease (a frequent cause of indigestion and heartburn), dyspepsia (indigestion) or gastric ulcers. In the UK, five PPIs are available on prescription: omeprazole, esomeprazole, pantoprazole, rabeprazole, and lansoprazole. Omeprazole is also available over the counter (Losec).
PPIs are used to treat the gastrointestinal disorders, oesophageal reflux disease (a frequent cause of indigestion and heartburn), dyspepsia (indigestion) or gastric ulcers. In the UK, five PPIs are available on prescription: omeprazole, esomeprazole, pantoprazole, rabeprazole, and lansoprazole. Omeprazole is also available over the counter (Losec).
Clopidogrel can cause side effects on the gastrointestinal system and is therefore frequently prescribed together with a PPI.
Interaction
Several studies have found that the use of PPIs lowered the clinical effectiveness of clopidogrel in preventing the recurrence of atherothrombotic events in patients who have previously had a serious heart condition (including coronary artery restenosis or heart attack).
Several studies have found that the use of PPIs lowered the clinical effectiveness of clopidogrel in preventing the recurrence of atherothrombotic events in patients who have previously had a serious heart condition (including coronary artery restenosis or heart attack).
For further information, see:
- Pezalla E, et al. Initial assessment of clinical impact of a drug interaction between clopidogrel and proton pump inhibitors. J Am Coll Cardiol 2008; 52: 1038 (external link).
- Ho M, et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 2009; 301: 937(external link).
- Society for Cardiovascular Angiography and Interventions (external link) statement on “A national study of the effect of individual proton pump inhibitors on cardiovascular outcomes in patients treated with clopidogrel following coronary stenting: The Clopidogrel Medco Outcomes Study”.
- Juurlink D, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ 2009; 180: 713–18 (external link).
Which PPI?
At present this advice applies to all PPIs. More evidence is required before any specific recommendations can be made on the extent of which the individual PPIs may interact with clopidogrel.
At present this advice applies to all PPIs. More evidence is required before any specific recommendations can be made on the extent of which the individual PPIs may interact with clopidogrel.
Alternatives to PPIs
Other acid-lowering medicines, such as H2 blockers or antacids, would not be expected to interact with clopidogrel. However, there are currently no substantial data from clinical outcome studies to support this.
Other acid-lowering medicines, such as H2 blockers or antacids, would not be expected to interact with clopidogrel. However, there are currently no substantial data from clinical outcome studies to support this.
Advice for healthcare professionals
- The need for PPI therapy in patients who are also taking clopidogrel should be reviewed at the next appointment. Use of these medicines together should be avoided unless considered essential
- PPIs should be prescribed in line with their licensed indications where possible
- Check whether patients who are taking clopidogrel are using over-the-counter PPI omeprazole and consider whether another gastrointestinal therapy would be more suitable
Questions and answers for patients
1. What is clopidogrel?
Clopidogrel, otherwise known as Plavix, reduces the ability of blood to form harmful clots. It is prescribed for people who have recently had acute coronary syndrome (a heart attack or unstable angina) to prevent them from having another episode. It is also prescribed for people who have had a stroke which was caused by a blood clot.
Clopidogrel, otherwise known as Plavix, reduces the ability of blood to form harmful clots. It is prescribed for people who have recently had acute coronary syndrome (a heart attack or unstable angina) to prevent them from having another episode. It is also prescribed for people who have had a stroke which was caused by a blood clot.
2. What is a Proton Pump Inhibitor?
Proton pump inhibitors, or PPIs, are a class of medicines that are used to treat gastro-oesophageal reflux disease including heartburn, regurgitation and pain on swallowing, gastric and duodenal ulcers. They are also used to prevent stomach ulcers in patients who are taking aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or diclofenac. PPIs are also used as part of combination treatment to help eradicate Helicobacter pylori infection.
Proton pump inhibitors, or PPIs, are a class of medicines that are used to treat gastro-oesophageal reflux disease including heartburn, regurgitation and pain on swallowing, gastric and duodenal ulcers. They are also used to prevent stomach ulcers in patients who are taking aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or diclofenac. PPIs are also used as part of combination treatment to help eradicate Helicobacter pylori infection.
Since clopidogrel is often given with aspirin, which can cause heartburn and stomach ulcers, PPIs are very often prescribed for patients on clopidogrel.
3. What medicines does the class of Proton Pump Inhibitors include?
Omeprazole (Losec), esomeprazole (Nexium), lansoprazole (Zoton), pantoprazole (Protium) and rabeprazole (Pariet) are all PPIs that are available in the UK.
Omeprazole (Losec), esomeprazole (Nexium), lansoprazole (Zoton), pantoprazole (Protium) and rabeprazole (Pariet) are all PPIs that are available in the UK.
4. Why are clopidogrel and Proton Pump Inhibitors in the news?
Several studies have recently shown that clopidogrel is less effective in preventing the recurrence of unstable angina, heart attack and stroke in patients who are also taking a PPI. This issue has recently been considered by the European Committee for Medicinal Products for Human Use (CHMP), and they have recommended that information for prescribers and patients is updated.
Several studies have recently shown that clopidogrel is less effective in preventing the recurrence of unstable angina, heart attack and stroke in patients who are also taking a PPI. This issue has recently been considered by the European Committee for Medicinal Products for Human Use (CHMP), and they have recommended that information for prescribers and patients is updated.
5. What is the new advice?
CHMP has advised that patients who are taking clopidogrel should not take a PPI at the same time unless it is absolutely necessary.
CHMP has advised that patients who are taking clopidogrel should not take a PPI at the same time unless it is absolutely necessary.
6. Does the new advice apply to all PPIs?
Yes, including omeprazole that you can buy over-the-counter.
Yes, including omeprazole that you can buy over-the-counter.
Although the strength of the evidence for an interaction between clopidogrel and PPIs varies for each member of the class, studies that have evaluated the effect of taking clopidogrel and PPIs on the rate of heart attack or stroke suggest that the interaction may occur with all members of the class.
7. What should I do if I am taking clopidogrel and a PPI?
There is no need for urgent action. Do not stop taking your medicines but seek advice from your doctor as soon as is convenient. Your doctor will advise whether you need to continue your PPI.
There is no need for urgent action. Do not stop taking your medicines but seek advice from your doctor as soon as is convenient. Your doctor will advise whether you need to continue your PPI.
If you normally buy your PPI (omeprazole) from a pharmacy, you should continue to take your clopidogrel as normal, but speak to your doctor at a routine appointment to see if it is still advisable to use omeprazole, or whether another treatment would be more suitable.
8. Are there any alternative to PPIs that don't interact with clopidogrel?
In theory other medicines for preventing heartburn and stomach ulcers would not be expected have the same effect on clopidogrel as the PPIs. However, there is currently insufficient evidence to recommend an alternative.
In theory other medicines for preventing heartburn and stomach ulcers would not be expected have the same effect on clopidogrel as the PPIs. However, there is currently insufficient evidence to recommend an alternative.
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