Previous changes

September 2023 — minor update. A reference to a study about the risks of antiplatelet therapy has been added to the basis for recommendation in the section on preventing dyspepsia. The wording relating to antiplatelets and atrial fibrillation has been revised. 

August 2023 — minor update. Revised the wording in the Which antiplatelet treatment section. Removed detail on secondary care treatments. Basis for recommendation section also revised to align with these changes in the treatment section. 

June 2023 — reviewed. A literature search was conducted in May 2023 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic. The topic has been restructured to reflect current guidance which does not recommend the routine use of antiplatelets for primary prevention. Minor changes to recommendations have been made in line with current UK and European guidelines.

November 2022 — minor update. A new caution has been added when prescribing ticagrelor as the manufacturer advises caution relating to people with sleep apnoea. 

July 2022 — minor update. Added potential drug interaction for rosuvastatin the manufacturer advises that ticagrelor might affect renal excretion of rosuvastatin, increasing risk for rosuvastatin accumulation. The exact mechanism is not known, but in some cases, concomitant use led to renal function decrease, increased creatinine phosphokinase level and rhabdomyolysis.

April 2022 — minor update. Added adverse effect of bradyarrhythmia and AV block for people taking ticagrelor in line with revised manufacturer's SPC. 

August 2020 — minor update. Drug interaction of rifampicin and clopidogrel added in line with revised manufacturer's SPC. 

September 2018 — minor update. Timing of discontinuation of ticagrelor prior to elective surgery has been changed from 7 to 5 days.

May to June 2018 — reviewed. A literature search was conducted in May 2018 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic. 

October 2015 — minor update. Based on an update to the Summary of Product Characteristics for Plavix® (clopidogrel), the list of CYP2C19 inhibitors that may interact with clopidogrel has been amended so that it now lists strong or moderate CYP2C19 inhibitors (ciprofloxacin, cimetidine, oxcarbazepine, and chloramphenicol have been removed).

May 2015 — minor update. Gynaecomastia has been added as a rare adverse effect of clopidogrel.

January 2014 — minor update. Minor update to the text to reflect recently published advice from the Medicines and Healthcare products Regulatory Agency (MHRA) regarding the rare but serious adverse effect of acquired haemophilia associated with clopidogrel.

August 2013 — reviewed. A literature search was conducted in August 2013 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. The structure of this topic has been changed to improve clarity and there are some changes to the recommendations. Prescribing information on prasugrel and ticagrelor is now included, and clopidogrel (instead of aspirin and dipyridamole) is now recommended as the preferred antiplatelet for use after a transient ischaemic attack.

June 2013 — minor update. The 2013 QOF options for local implementation have been added to this topic.

October 2012 — minor update. The 2012 QIPP options for local implementation have been added to this topic.

April 2012 — minor update. The 2012/2013 QOF indicators have been added to this topic. 

June 2011 — minor update. The Medicines and Healthcare products Regulatory Agency (MHRA) has issued drug safety advice regarding the rare association of prasugrel with reports of serious hypersensitivity reactions. In addition the 2011/2012 QOF indicators and the 2010/2011 QIPP options for local implementation have been added to this topic. 

February 2011 — topic structure revised to ensure consistency across CKS topics — no changes to clinical recommendations have been made.

February 2011 — updated. The new recommendations from NICE technology appraisal 210 Clopidogrel and modified-release dipyridamole for the prevention of occlusive vascular events have been incorporated into this topic. 

December 2010 — minor update to the Supporting evidence section on Adverse effects of aspirin and clopidogrel. 

September 2010 — minor update. A new meta-analysis evaluating aspirin for primary prevention of cardiovascular disease in people with diabetes has been added to the Supporting evidence section.

April 2010 — minor update. The Medicines and Healthcare products Regulatory Agency (MHRA) has issued revised advice regarding the interaction between clopidogrel and proton pump inhibitors. Omeprazole and esomeprazole should not be used with clopidogrel. However, the current evidence does not support extending this advice to other PPIs. Advice from SIGN that aspirin is no longer recommended for primary prevention of cardiovascular disease in people with diabetes has also been added. 

December 2009 — minor update. Advice about venlafaxine in people taking low-dose aspirin has been added to the section on Drug interactions for low-dose aspirin. The Supporting evidence section on antiplatelet treatment for primary prevention of cardiovascular disease, and the recommendations on when to consider antiplatelet treatment for primary prevention of cardiovascular disease have also been updated.

November 2009 — minor update. Other inhibitors of CYP219C added to the section on Drug interactions for clopidogrel. Advice about choice of antidepressant in people taking low-dose aspirin has been added to the section on Drug interactions for low-dose aspirin.

October 2009 — minor update. Typographical error corrected. A reminder from the MHRA that aspirin is not licensed for use in primary prevention of vascular events has also been added. 

September 2009 — minor update. The MHRA advises that cimetidine and clopidogrel should not be co-prescribed because cimetidine inhibits the Cytochrome P450 enzyme CYP2C19. 

February to July 2009 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence.

There have been no major changes to the recommendations.

June 2009 — minor update. Typographical error corrected. 

May 2009 — minor update. The GMS quality indicators section in Goals and outcome measures has been renamed QOF indicators.

February 2009 — minor typographical corrections made to Supporting evidence section. 

November 2008 — minor update to the Supporting evidence section on strategies to reduce risk of aspirin-induced gastrointestinal complications, making it clear that proton pump inhibitors for gastroprotection are all similarly effective at licensed doses, and that standard doses of proton pump inhibitors (at doses licensed for gastroprotection) should be used where necessary. 

January 2008 — updated to include information on what to do if blood pressure control deteriorates in someone taking aspirin for primary prevention of cardiovascular disease. 

April to June 2006 — written. Validated in September 2006 and issued in October 2006.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 May 2023.

HTAs (Health Technology Assessments)

No new HTAs since 1 May 2023.

Economic Appraisals

No new economic appraisals relevant to England since 1 May 2023.

Systematic reviews and meta-analyses

No New systematic reviews or meta-analyses since 1 May 2023.

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 May 2023.

New policies

No new national policies or guidelines since 1 May 2023.

New safety alerts

No new safety alerts since 1 May 2023.

Changes in product availability

No changes in product availability since 1 May 2023.

When should antiplatelet treatment be prescribed for the prevention of cardiovascular disease?

• Antiplatelet treatment is usually initiated by specialists. Clinicians in primary care are likely to be involved in continuing, monitoring, and reviewing the need for ongoing use. Clinicians in primary care may also be involved in the initial treatment of suspected acute coronary syndrome (ACS) or suspected transient ischaemic attack (TIA) within the last week, which may include giving a loading dose of 300 mg aspirin. This is not further discussed in this CKS topic. See the topics chest pain and Stroke and TIA for further information.
• Antiplatelet treatment should be prescribed for the secondary prevention of cardiovascular events in people with:
  • Acute coronary syndrome (ACS).
  • Stable angina.
  • Peripheral arterial disease (PAD).
• Antiplatelet treatment should also be prescribed for the secondary prevention of cardiovascular events in people after:
  • Myocardial infarction (MI).
  • Stroke or transient ischaemic attack (TIA).
  • Angiography, percutaneous coronary intervention (PCI), or coronary bypass surgery.
• Antiplatelet treatment is also sometimes prescribed for secondary prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE) in people who decline continued anticoagulant treatment.
• For further information, see the CKS topics on Angina, MI - secondary prevention, Atrial fibrillation, and Stroke and TIA.

Which antiplatelet treatment should I prescribe for secondary prevention of cardiovascular disease?

Antiplatelet treatment is not routinely recommended for primary prevention of cardiovascular disease.

• For secondary prevention low dose aspirin is the first choice antiplatelet medication.

Acute coronary syndrome (ACS)

• Antiplatelet treatment will be managed by specialists.
• ACS includes unstable angina, non-ST segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI).
  • For all people with ACS initial treatment is with aspirin 300 mg, followed by a low dose of 75 mg aspirin once a day indefinitely, unless contraindicated.
  • Clopidogrel may be used as an alternative for people with aspirin hypersensitivity.
• Dual antiplatelet therapy (DAPT) with aspirin 75 mg once daily plus a second antiplatelet should be offered, unless contraindicated, and continued for up to 12 months. Individual risk factors may lead to this period being extended (for example, people who tolerate DAPT and are at high risk) or shortened (those at high bleeding risk).
• Recommended doses are as follows:
  • Prasugrel 5 mg once daily (10 mg if body weight is 60 kg or more and the patient is under the age of 75).
  • Ticagrelor 90 mg twice daily for up to 12 months (reduced to 60 mg twice daily if treatment is extended beyond 12 months).
  • Clopidogrel 75 mg once daily.

Atrial fibrillation (AF)

• Aspirin is not indicated as an antiplatelet treatment in people with AF. For further information see the CKS topic on Atrial fibrillation.

Peripheral arterial disease (PAD) 

• Clopidogrel 75 mg daily is the preferred antiplatelet medication to prevent occlusive vascular events. 
• If clopidogrel is contraindicated or not tolerated, low-dose aspirin may be considered as an alternative.
• Specialists may recommend a combination of rivaroxaban 2.5 mg twice a day plus aspirin for people at higher risk of ischaemic events and a low risk of bleeding.

Stroke, or transient ischaemic attack (TIA)

• Antiplatelet treatment will be managed by specialists.  
  • In the acute phase people dual antiplatelet therapy is likely to be prescribed for 3-4 weeks:
    • Clopidogrel (300 mg initial dose, then 75 mg daily) plus aspirin (300 mg initial dose, then 75 mg daily for 21 days) followed by long-term clopidogrel monotherapy.
    • Alternatively ticagrelor (180 mg initial dose then 90 mg twice daily) plus aspirin (300 mg initial dose then 75 mg daily for thirty days) followed by monotherapy with ticagrelor 90 mg twice daily or clopidogrel 75 mg daily.
  • For people where dual therapy is not considered appropriate, clopidogrel is given alone, 300 mg as an initial dose then 75 mg daily.
  • For people who cannot tolerate clopidogrel the alternatives include:
    • Aspirin 75 mg daily.
    • Modified–release dipyridamole (200 mg twice a day) combined with low-dose aspirin.
    • Modified-release dipyridamole alone.

Surgical coronary intervention

• Percutaneous coronary intervention (PCI)
  • For people with stable coronary artery disease who are undergoing elective PCI, aspirin 75 mg daily with clopidogrel 75 mg daily is initiated in secondary care and continued for 6 months.
    
    • For people at high risk of bleeding, a shortened duration of DAPT for 1- 3 months may be considered appropriate.
    • For people with high ischaemic risk who have tolerated DAPT without a bleeding complication this may be extended for up to 36 months, depending on specialist advice. 
    • Ticagrelor or prasugrel may also be considered instead of clopidogrel after more complex interventions, depending on specialist advice. 
• Coronary artery bypass grafting (CABG)
  • Antiplatelet treatment will be managed by specialists.

How can I help prevent dyspepsia?

• If the person is taking a dose of aspirin higher than 75 mg daily, reduce the dose to 75 mg daily (unless a higher dose is indicated) to be taken after food.
  • Do not prescribe enteric-coated aspirin.
• Provide general advice to help reduce gastrointestinal (GI) adverse effects. For more information, see the section on Initial management in the CKS topic on Dyspepsia - unidentified cause. 
• Consider testing for and treating Helicobacter pylori if the person has a history of ulcer disease or upper GI bleeding, unless previously tested and treated for this.
• If the person has a high risk of GI adverse effects (for example bleeding) and is taking:
  • Low-dose aspirin alone, or in combination with ticagrelor or prasugrel:
    • Co-prescribe a proton pump inhibitor (PPI), such as lansoprazole, omeprazole, or pantoprazole for gastroprotection.
    • For more information, see the section on Licensed doses of proton pump inhibitors used for gastroprotection for people who require continued NSAID treatment in the CKS topic on NSAIDs - prescribing issues. 
  • Clopidogrel alone, or in combination with low-dose aspirin:
    • Co-prescribe a PPI, except omeprazole or esomeprazole.

How should I manage antiplatelet-induced dyspepsia?

• In people with alarm features, refer urgently using a suspected cancer pathway referral (for an appointment within 2 weeks).
  • For more information, see the CKS topic on Gastrointestinal tract (upper) cancers - recognition and referral. 
  • While waiting for endoscopy, antiplatelet treatment may be continued
  • Consider advising or prescribing a simple antacid to relieve dyspepsia (as proton pump inhibitors [PPIs] and H2-receptor antagonists should be avoided for at least 2 weeks before endoscopy).
• In people without alarm features:
  • Ensure that general measures to reduce the risk of gastrointestinal (GI) adverse effects have been taken. For more information, see the CKS topic on Dyspepsia - unidentified cause. 
  • Prescribe or advise an antacid or alginate to use for short-term 'as required' relief of dyspeptic symptoms.
  • Offer empirical treatment with a full-dose PPI for 1 month.
  • Offer test and treat for Helicobacter pylori (if the person's status is unknown).
    • Leave a two-week washout period after PPI use before testing for H. pylori.
    • For information on testing for and treating H. pylori as well as prescribing PPIs, see the CKS topic on Dyspepsia - unidentified cause.
  • If symptoms recur after PPI treatment or eradication treatment, prescribe the lowest dose of PPI to control symptoms.
  • Review maintenance treatment at least annually.
• If taking clopidogrel alone or in combination with aspirin:
  • Avoid co-prescribing omeprazole or esomeprazole with clopidogrel — use an alternative PPI, or consider prescribing an H2-receptor antagonist (H2RA) for 1 month.
• Refer to secondary care for investigation if symptoms persist despite treatment.

How should I manage switching of antiplatelet treatments?

• Switching between antiplatelet medication may be required if the current treatment is unsuitable.
• If switching from clopidogrel to:
  • Ticagrelor — start 90 mg twice daily, 24 hours after the last clopidogrel dose.
  • Prasugrel — start 10 mg daily, 24 hours after last clopidogrel dose. 
• If switching from prasugrel to:
  • Clopidogrel — start 75 mg daily, 24 hours after the last prasugrel dose.
  • Ticagrelor — start 90 mg twice daily, 24 hours after the last prasugrel dose. 
• If switching from ticagrelor to:
  • Clopidogrel — give a loading dose of 600 mg, 24 hours after the last ticagrelor dose. Then continue with 75 mg daily.
  • Prasugrel — give a 60 mg loading dose, 24 hours after the last ticagrelor dose. Then continue with 10 mg daily.
• If switching in an acute setting, loading doses are always recommended. The above recommendations apply to switching in a chronic setting.

How should I manage people taking antiplatelets who are undergoing surgery or dental treatment?

• Advise people taking antiplatelet medications to inform dentists or medical teams before any surgery is scheduled. 
• Dual antiplatelet therapy (DAPT) increases the risk of surgical bleeding complications. 
  • The bleeding risk is further increased if ticagrelor or prasugrel are used rather than clopidogrel.
• For people undergoing dental surgery antiplatelet therapy should continue uninterrupted.
• For people undergoing coronary artery bypass grafting (CABG), discontinue:
  • Ticagrelor 3–7 days before surgery.
  • Clopidogrel 5–7 days before surgery.
  • Prasugrel at least 7 days before surgery.
• For people undergoing non-cardiac surgery, the risk of bleeding and thrombosis should be considered by the specialist team.

Contraindications and cautions

• Do not prescribe aspirin to children younger than 16 years of age due to the risk of Reye's syndrome (unless specifically indicated by a specialist — for example for Kawasaki's disease).
• Do not prescribe aspirin to people with: 
  • A history of true hypersensitivity to aspirin, salicylates or another nonsteroidal anti-inflammatory drug (NSAID).
    • Symptoms of hypersensitivity to aspirin or salicylates include bronchospasm, urticaria, angioedema, and rhinitis. These can occur in isolation or in combination and can lead to severe or life-threatening reactions.
  • Active pathological bleeding, such as peptic ulcer or other gastrointestinal or intracranial haemorrhage.
  • Severe hepatic impairment.
  • Severe renal impairment.
  • Bleeding disorders or coagulation disorders such as haemophilia or thrombocytopenia.
• Prescribe aspirin with caution to people with:
  • Allergic disease (asthma, hay fever, urticaria, and nasal polyps as it may promote bronchospasm or an asthma attack).
  • Anaemia.
  • Asthma.
  • Chronic respiratory disease.
  • Dehydration.
  • Gout.
  • Hepatic impairment.
  • Previous peptic ulceration.
  • Renal impairment.
  • Thyrotoxicosis.
  • Uncontrolled hypertension.
• Also prescribe aspirin with caution in:
  • The elderly.
  • People at high risk of increased bleeding — for example, those receiving treatment with warfarin, nonsteroidal anti-inflammatory drugs, corticosteroids, or other drugs known to increase bleeding.
    • For further information, see drug interactions.

[EMC, 2021; BNF, 2023]

Adverse effects

• Adverse effects of low-dose aspirin include: 
  • Asthma, bronchospasm, dyspnoea.
  • Gastrointestinal irritation (dyspepsia).
    • For further information, see Preventing dyspepsia and Managing antiplatelet-induced dyspepsia.
  • Haemorrhage, including gastrointestinal haemorrhage (occasionally major), and subconjunctival haemorrhage.
  • Hypersensitivity reactions include angioedema, allergic oedema, and anaphylactic reactions.
  • Increased bleeding time/tendencies.
  • Rhinitis.
  • Skin reactions.

[EMC, 2021; BNF, 2023]

Drug interactions

• The risk of bleeding is increased when low-dose aspirin is combined with other drugs that can increase the risk of bleeding. If these drugs are used concurrently with low-dose aspirin, consider the need for gastroprotection with a proton pump inhibitor (such as omeprazole) or a histamine antagonist (such as ranitidine). Drugs that can increase the risk of bleeding include:
  • Other antiplatelet drugs (such as clopidogrel, prasugrel, or ticagrelor).
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) (for example diclofenac, ibuprofen, naproxen).
  • Oral and parenteral anticoagulants  —  for example, warfarin or heparin or direct oral anticoagulants (DOACs) — low-dose aspirin and oral anticoagulants are usually co-prescribed on the advice of a specialist. Close monitoring is required.
  • Selective serotonin reuptake inhibitors (SSRIs - such as citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline) and serotonin and noradrenaline reuptake inhibitors (SNRIs - duloxetine, venlafaxine)  — consider alternatives that may be safer, such as trazodone, mianserin, mirtazapine, or reboxetine.
  • Other drugs known to increase gastrointestinal bleeding (for example corticosteroids).
• Methotrexate — the toxicity of methotrexate may be enhanced by aspirin. 
  • The risk of toxicity is greater in people receiving higher doses of methotrexate (15 mg daily or more per week) and aspirin due to the decreased renal clearance of methotrexate. The use of concomitant use of aspirin with methotrexate above this dose is contraindicated.
  • Ensure that the individual is monitored regularly for adverse effects and is advised on when to seek medical advice (for example, if they have a sore throat, dyspnoea, or cough). For further information on monitoring a person taking methotrexate and on the signs of methotrexate toxicity, see the CKS topic on DMARDs.
• NSAIDs — there may be a loss of aspirin antiplatelet effect if taken concurrently with an NSAID.
  • For further information, see the CKS topic on NSAIDs - prescribing issues.
  • This interaction is thought not to occur with occasional ibuprofen use.
• Sulphonylureas — aspirin may increase the hypoglycaemic effect.

 [EMC, 2021; BNF, 2023]

Pregnancy and breastfeeding

Pregnancy

• Low doses (less than 100 mg/day) appear to be safe, but require specialised monitoring.
  •  The manufacturer advises that aspirin should not be given in the first and second trimesters in higher doses unless clearly necessary.
• Antiplatelet doses should be used with caution in the third trimester.
  • The manufacturer advises that doses of 100 mg/day and higher are contraindicated during the third trimester of pregnancy.

Breastfeeding

• Long-term use of aspirin should be avoided in women who are breastfeeding.
  • Low quantities of salicylates and their metabolites are excreted in breastmilk. Breastfeeding needs to be discontinued if low-dose aspirin is used long-term or in higher doses.

[EMC, 2021; BNF, 2023]

Contraindications and cautions

• Do not prescribe clopidogrel to people with:
  • Active pathological bleeding, such as peptic ulcer or intracranial haemorrhage.
  • Severe hepatic impairment.
• Prescribe clopidogrel with caution to people:
  • At risk of increased bleeding from trauma, surgery, or other pathological conditions (for elective surgery where the antiplatelet effect is temporarily not desirable, clopidogrel should be discontinued 7 days prior to surgery).
  • Taking other drugs known to increase bleeding risk (for example, nonsteroidal anti-inflammatory drugs, corticosteroids, or selective serotonin reuptake inhibitors).
  • With renal impairment.
  • With hepatic impairment.
  • With hypersensitivity to thienopyridines (for example prasugrel) due to risk of cross-sensitivity.

 [EMC, 2022a; BNF, 2023]

Adverse effects

• Blood and lymphatic system — thrombocytopenia, leucopenia, and eosinophilia (uncommon).
  • Rarely or very rarely: neutropenia, thrombotic thrombocytopenia purpura (TTP), aplastic anaemia, acquired haemophilia A, and granulocytopenia.
• Eye — conjunctival, ocular, or retinal bleeding (uncommon). 
• Gastrointestinal (GI)— GI haemorrhage, abdominal pain, diarrhoea, dyspepsia (common), gastric ulcer, duodenal ulcer, gastritis, vomiting, nausea, constipation, and flatulence (uncommon).
  • Very rarely: GI and retroperitoneal haemorrhage with fatal outcome, pancreatitis, and colitis.
• Respiratory — epistaxis (common).
  • Rarely: haemoptysis, pulmonary haemorrhage, bronchospasm, interstitial pneumonitis, and eosinophilic pneumonia.
• Skin and subcutaneous tissue — bruising (common), rash, pruritus, and skin bleeding (uncommon).
  • Very rarely: toxic epidermal necrolysis, Stevens-Johnson Syndrome, erythema multiforme, acute generalized exanthematous pustulosis (AGEP), angioedema, drug-induced hypersensitivity syndrome, and drug rash with eosinophilia and systemic symptoms (DRESS).
• Vascular — haematoma (common).
  • Very rarely: serious haemorrhage, vasculitis, and hypotension.
• Immune system disorders — cross-sensitivity with thienopyridines and insulin autoimmune syndrome which can lead to severe hypoglycaemia, particularly in patients with HLA DRA4 subtype (this is more frequent in the Japanese population).
• Other rare or very rare adverse effects include:
  • Acute liver failure, hepatitis.
  • Fever.
  • Gynaecomastia.
  • Hallucinations, confusion.
  • Kounis syndrome.
  • Serum sickness, anaphylactoid reactions.
  • Vertigo.

 [EMC, 2022a; BNF, 2023]

Drug interactions

Potential interactions with clopidogrel include: 

• Montelukast — levels may be increased by clopidogrel. Monitor for adverse effects and reduce the montelukast dose if required.
• Pioglitazone — levels of pioglitazone are increased. Monitor for adverse effects and reduce the dose if required.
• Repaglinide — levels may be increased by clopidogrel. Monitor blood glucose concentrations closely and adjust the repaglinide dose if required.
• Rifampicin — metabolism of clopidogrel to its active metabolite is induced slightly increasing antiplatelet effect. Bear this in mind if unexplained bleeding occurs. The manufacturer discourages concurrent use.
• Rosuvastatin — clopidogrel may increase exposure to rosuvastatin.
• Increased risk of bleeding if clopidogrel is combined with other drugs that also increase the risk of bleeding. Examples include: 
  • Antiplatelets — aspirin, prasugrel, and ticagrelor.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) — ibuprofen, diclofenac, and COX-2 inhibitors.
  • Oral and parenteral anticoagulants— warfarin, or heparin or direct oral anticoagulants (DOACs). Concomitant use of clopidogrel with oral anticoagulants is not recommended.
  • Selective serotonin reuptake inhibitors (SSRIs).
  • Serotonin and noradrenaline reuptake inhibitors (SNRIs) —  venlafaxine and duloxetine.
• Drugs which when taken concurrently with clopidogrel may reduce the antiplatelet effect include:
  • Antifungals (voriconazole, fluconazole, and ketoconazole) —avoid concurrent use.
  • Carbamazepine — avoid concurrent use.
  • Efavirenz — avoid concurrent use.
  • Grapefruit juice — inhibition of platelet aggregation reduced. Grapefruit juice should be avoided when taking clopidogrel.
  • Moclobemide — avoid concurrent use.
  • Omeprazole and esomeprazole — use only when the risk of gastrointestinal bleeding outweighs the risk of clopidogrel treatment failure (reduction of the effect is less pronounced with pantoprazole and lansoprazole, and there is no evidence that H2 blockers or antacids interfere with the antiplatelet action of clopidogrel).
  • Opioids have the potential to delay gastric emptying which may reduce the absorption of clopidogrel.

 [EMC, 2022a; BNF, 2023]

Pregnancy and breastfeeding

Pregnancy

• Clopidogrel should be avoided in women who are pregnant as a precautionary measure, as there are no available data on exposure in pregnancy.

Breastfeeding

• It is unknown whether clopidogrel is excreted in breastmilk. The manufacturer advises that breastfeeding should be discontinued during treatment with clopidogrel.

 [EMC, 2022a; BNF, 2023]

Contraindications and cautions

• Prescribe dipyridamole with caution to people with:
• • Aortic stenosis.
  • Coagulation disorders.
  • Heart failure.
  • Hypotension.
  • Left ventricular outflow obstruction.
  • Myasthenia gravis.
  • Unstable angina, or a recent myocardial infarction, or severe coronary artery disease.

[BNF, 2023; EMC, 2023]

Adverse effects

• Cardiac — angina pectoris (common) and tachycardia (frequency unknown).
• Gastrointestinal — diarrhoea, nausea (very common), and vomiting (common).
• Nervous system — headache and dizziness (very common).
• Other adverse effects include:
  • Bronchospasm.
  • Hypersensitivity and angioedema.
  • Hypotension and hot flushes (due to vasodilatory effect).
  • Haemorrhage.
  • Myalgia.
  • Post-procedural/operative haemorrhage.
  • Rash and urticaria.
  • Thrombocytopenia.

[BNF, 2023; EMC, 2023]

Drug interactions

• Adenosine — dipyridamole exposure increases plasma levels and cardiovascular effects of adenosine. Avoid concurrent use or adjust the adenosine dose.
• Anti-hypertensives — hypotensive effect may be increased.
• Cholinesterase inhibitors (neostigmine and pyridostigmine) — concurrent use with dipyridamole may antagonise these drugs. Dipyridamole should be used with caution in people with myasthenia gravis as this may therefore be aggravated.
• Dobutamine — potentially hazardous hypotension if taken with dipyridamole. Avoid concurrent use.
• Drugs which raise the gastric pH (antacids, H2 blockers, PPIs) — bioavailability of immediate-release dipyridamole may be reduced. Modified release preparations of dipyridamole are not affected.
• Increased risk of bleeding if clopidogrel is combined with other drugs that also increase the risk of bleeding. Examples include: 
  • Anticoagulants — warfarin, direct oral anticoagulants (DOACs), and heparin.
  • Antiplatelets — for example, aspirin, clopidogrel, prasugrel, and ticagrelor.
  • Non-steroidal anti-inflammatory drugs (NSAIDs) —  for example diclofenac, ibuprofen, and naproxen.
  • Selective serotonin reuptake inhibitors (SSRIs) — for example, citalopram, fluoxetine, and sertraline.
  • Serotonin and noradrenaline reuptake inhibitors (SNRIs) — venlafaxine and duloxetine.

[BNF, 2023; EMC, 2023]

Pregnancy and breastfeeding

Pregnancy

• Dipyridamole is not known to be harmful in pregnancy. However, the manufacturer advises that it should only be used if the benefits outweigh the possible risks.

Breastfeeding

• Dipyridamole is excreted in breastmilk in small amounts.
• The manufacturer advises that it should only be used during breastfeeding if essential.

[BNF, 2023; EMC, 2023]

Contraindications and cautions

• Do not prescribe prasugrel to people with:
  • Active pathological bleeding.
  • A history of stroke or transient ischaemic attack.
  • Severe hepatic impairment.
• Prescribe prasugrel with caution to people:
  • At increased risk of bleeding (for example from recent trauma, surgery, gastrointestinal bleeding, or active peptic ulcer disease).
  • Taking drugs that increase the risk of bleeding (for example aspirin, clopidogrel, oral anticoagulants, and non-steroidal anti-inflammatory drugs).
  • Who are elderly (aged over 75 years) or weigh less than 60 kg — a maintenance dose of 5 mg daily should be used.
  • With renal or hepatic impairment.
  • Undergoing elective surgery — discontinue 7 days before if antiplatelet effect is not desirable.

[EMC, 2019; BNF, 2023]

Adverse effects

• Gastrointestinal (GI) — GI haemorrhage (common), retroperitoneal haemorrhage, rectal haemorrhage, and gingival bleeding (uncommon).
• Blood and lymphatic system — anaemia (common).
  • Rarely: thrombocytopenia.
  • Frequency unknown: thrombotic thrombocytopenia purpura (TTP).
• Other adverse effects include:
  • Epistaxis, haemoptysis.
  • Eye haemorrhage.
  • Haematuria.
  • Haematoma.
  • Hypersensitivity, angioedema.
  • Intracranial haemorrhage.
  • Rash, ecchymosis.

[EMC, 2019; BNF, 2023]

Drug interactions

• Increased risk of bleeding if prasugrel is combined with other drugs that also increase the risk of bleeding. Examples include: 
  • Other antiplatelets drugs — aspirin, clopidogrel, or ticagrelor.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) — for example, ibuprofen, diclofenac, naproxen, and COX-2 inhibitors.
  • Oral and parenteral anticoagulants — for example, warfarin, heparin, and direct acting oral anticoagulants (DOACs).
  • Selective serotonin reuptake inhibitors (SSRIs) — for example, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline.
  • Serotonin and noradrenaline reuptake inhibitors (SNRIs) — venlafaxine and duloxetine.

[EMC, 2019; BNF, 2023] 

Pregnancy and breastfeeding

Pregnancy

• The manufacturer advises that prasugrel should only be used in women who are pregnant if the potential benefits outweigh the risks.

Breastfeeding

• It is unknown whether prasugrel is excreted in breastmilk.
• Use in women who are breastfeeding is not recommended.

[EMC, 2019; BNF, 2023]

Contraindications and cautions

• Do not prescribe ticagrelor to people with:
  • Active pathological bleeding.
  • A history of intracranial haemorrhage.
  • Severe hepatic impairment.
• Do not prescribe ticagrelor to people who are on strong CYP3A4 inhibitors (for example, ketoconazole, clarithromycin, nefazodone, ritonavir, and atazanavir) — concomitant use may lead to a substantial increase in exposure to ticagrelor.
• Prescribe ticagrelor with caution to people:
  • A history of asthma or chronic obstructive pulmonary disease.
  • A history of sleep apnoea. 
  • A history of hyperuricaemia.
  • At increased risk of bleeding (for example from recent trauma, surgery, gastrointestinal bleeding, and coagulation disorders).
  • At increased risk of bradycardia, sick sinus syndrome, or second or third-degree AV block (unless a pacemaker is fitted).
  • Taking drugs that increase the risk of bleeding.
  • Undergoing elective surgery — discontinue 5 days before if antiplatelet effect is not desirable.

[EMC, 2022b; BNF, 2023]

Adverse effects

• Gastrointestinal (GI) — GI haemorrhage, diarrhoea, nausea, dyspepsia, constipation (common), and retroperitoneal haemorrhage (uncommon).
• Metabolism and nutrition — hyperuricaemia (very common), gout, and gouty arthritis (common).
• Nervous system — dizziness, syncope, headache (common), and intracranial haemorrhage (uncommon).
• Respiratory — dyspnoea (very common) and respiratory system bleedings (common).
• Cardiovascular — bradyarrhythmia and AV block (unknown frequency). 
• Other adverse effects include:
  • Bleeding into tumours.
  • Confusion.
  • Creatinine level increases.
  • Eye haemorrhage.
  • Hypotension.
  • Subcutaneous or dermal bleeding, tendency to bruise, rash pruritus.
  • Urinary tract bleeding.
  • Vertigo, ear haemorrhage.
  • Thrombotic thrombocytopenic purpura.

[EMC, 2022b; BNF, 2023]

Drug interactions

• Strong CYP3A4 inhibitors — the manufacturer warns that ketoconazole, clarithromycin, nefazodone, ritonavir, and atazanavir may cause a substantial increase in exposure to ticagrelor, and states that co-administration of ticagrelor with any of these drugs is contraindicated.
• Digoxin — plasma levels of digoxin are increased by ticagrelor. Monitor for adverse effects (bradycardia) and measure digoxin concentrations if necessary.
• Diltiazem, verapamil — concurrent use may moderately increase ticagrelor levels and cause additive bradycardia.
• Simvastatin — plasma concentrations of simvastatin are moderately increased by ticagrelor. Use a maximum of 40 mg simvastatin daily and advise people to report any unexplained muscle pain, tenderness or weakness.
• Rosuvastatin — manufacturer advises that ticagrelor might affect renal excretion of rosuvastatin, increasing the risk for rosuvastatin accumulation. The exact mechanism is not known, but in some cases concomitant use led to renal function decrease, increased creatinine phosphokinase level, and rhabdomyolysis.
• Increased risk of bleeding if ticagrelor is combined with other drugs that also increase the risk of bleeding. Examples include: 
  • Other antiplatelet drugs — aspirin, clopidogrel, or prasugrel.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) — for example, ibuprofen and diclofenac.
  • Oral and parenteral anticoagulants — warfarin, heparin, and direct oral anticoagulants (DOACs).
  • Selective serotonin reuptake inhibitors (SSRIs) — for example, citalopram, fluoxetine, and sertraline.
  • Serotonin and noradrenaline reuptake inhibitors (SNRIs) — venlafaxine and duloxetine.
• Drugs which when taken concurrently with ticagrelor may increase the antiplatelet effect include:
  • Antifungals (itraconazole, ketoconazole, and voriconazole) — concurrent use is contraindicated.
  • Ciclosporin — monitor for ticagrelor adverse effects.
  • Clarithromycin — concurrent use is contraindicated.
  • HIV protease inhibitors (atazanavir and ritonavir) — concurrent use is contraindicated. 
  • Grapefruit juice — be alert for ticagrelor adverse effects and advise the person to avoid grapefruit juice if necessary. The manufacturer advises this is unlikely to be clinically relevant for most patients.
  • Quinidine — monitor for ticagrelor adverse effects.
• Drugs which when taken concurrently with ticagrelor may reduce the antiplatelet effect include:
  • Carbamazepine.
  • Efavirenz.
  • Phenytoin.
  • Phenobarbital.
  • Rifampicin.
  • St John’s Wort.

[EMC, 2022b; BNF, 2023]

Monitoring

• Monitor renal function one month after starting treatment.

[EMC, 2022b; BNF, 2023] 

Pregnancy and breastfeeding

Pregnancy

• Ticagrelor is not recommended for use in women who are pregnant.

Breastfeeding

• Ticagrelor is excreted in breastmilk and a risk to newborns cannot be excluded. The manufacturer advises that ticagrelor should be avoided in women who are breastfeeding.

[EMC, 2022b; BNF, 2023]