- ACRONYMS AND DEFINITIONS
- ACS - Acute coronary syndrome (myocardial infarction or unstable angina)
- AHA - American Heart Association
- CAD - Coronary artery disease
- DAPT - Dual antiplatelet therapy
- MI - Myocardial infarction
- PAD - Peripheral artery disease
- PPI - Proton pump inhibitor (ex. Prilosec®, Protonix®, Nexium®, Prevacid®, etc.)
- P2Y12 INHIBITORS
Clopidogrel (Plavix®)
Dosage forms
Tablet
- 75 mg
- 300 mg
Dosing
Acute coronary syndrome
- Loading: 300 mg one time dose
- Maintenance: 75 mg once daily
- With maintenance dosing (75 mg/day), maximal platelet inhibition occurs within 5 - 10 days
- With a 300 - 600 mg loading dose, maximal platelet inhibition occurs within 12 - 15 hours.
- See AHA DAPT recommendations for a review of dual antiplatelet therapy after ACS
- May take without regard to food
Recent MI, recent stroke, or established PAD
- Dosing: 75 mg once daily
- Max: 75 mg once daily
- Do not give loading dose
Generic / Price
- YES/$Other
- The Plavix® PI recommends avoiding omeprazole (Prilosec®) and esomeprazole (Nexium®) when taking clopidogrel. See clopidogrel and PPIs for more.
- Clopidogrel may have reduced efficacy in CYP2C19 poor metabolizers (see CYP2C19 poor metabolizers for more)
Prasugrel (Effient®)
Dosage forms
Tablet
- 5 mg
- 10 mg
Dosing
Acute coronary syndrome
- Loading: 60 mg one time dose
- Maintenance: 10 mg once daily
- Max: 10 mg once daily
- In patients weighing < 60 kg (132 pounds), consider 5 mg once daily
- With a 60 mg loading dose, maximal platelet inhibition occurs within 2 - 4 hours
- See AHA DAPT recommendations for a review of dual antiplatelet therapy after ACS
- May take without regard to food
Generic / Price
- YES/$Other
- Efficacy and safety of the 5 mg dose has not been studied
- Not recommended in patients ≥ 75 years old
- Dispense and store Effient in its original container
- Keep container closed and do not remove desiccant from bottle
- Do not half or break tablets
Ticagrelor (Brilinta®)
Dosage forms
Tablet
- 60 mg
- 90 mg
Dosing
Acute coronary syndrome or history of MI
- Loading: 180 mg one time dose
- Maintenance: 90 mg twice daily during the first year after an ACS event, then 60 mg twice daily
- With a 180 mg loading dose, maximal platelet inhibition occurs around 2 hours
- Daily dose of aspirin when given with ticagrelor should be 75 - 100 mg. Higher doses of aspirin (> 100 mg) may decrease the effectiveness of ticagrelor.
- See AHA DAPT recommendations for a review of dual antiplatelet therapy after ACS
- May take without regard to food
CAD with no prior history of stroke or MI
- Dosing: 60 mg twice daily
- Daily dose of aspirin when given with ticagrelor should be 75 - 100 mg. Higher doses of aspirin (> 100 mg) may decrease the effectiveness of ticagrelor.
- May take without regard to food
- See THEMIS trial for more
Acute ischemic stroke or transient ischemic attack (TIA)
- Loading: 180 mg one time dose
- Maintenance: 90 mg twice daily for up to 30 days
- With a 180 mg loading dose, maximal platelet inhibition occurs around 2 hours
- Use ticagrelor with a loading dose of aspirin (300 to 325 mg) and a daily maintenance dose of aspirin of 75 to 100 mg
- May take without regard to food
- See THALES trial for more
Generic / Price
- NO/$$$$Other
- Tablet may be crushed, mixed with water, and drunk immediately. Glass should be refilled with water, stirred, and remaining contents drunk. The mixture may also be given via NG tube. Tube should be flushed after giving.
Ticlopidine (Ticlid®)
Dosage forms
Tablet
- 250 mg
Dosing
Stroke prevention
- Dosing: 250 mg twice a day
- Max: 250 mg twice a day
- Take with food. Food increases absorption and may help minimize GI upset.
Coronary artery stenting
- Dosing: 250 mg twice a day
- Max: 250 mg twice a day
- Take with food. Food increases absorption and may help minimize GI upset.
Generic / Price
- YES / Limited availability in U.S.- Kidney disease dosing
- Clopidogrel (Plavix®)
- Severe kidney disease (CrCl 5 - 15 ml/min): drug effect is reduced. Manufacturer makes no specific dosage recommendation
- Moderate kidney disease (CrCl 30 - 60 ml/min): drug effect is reduced. Manufacturer makes no specific dosage recommendation [12]
- Prasugrel (Effient®)
- No dose adjustment is necessary in kidney disease [13]
- Ticagrelor (Brilinta®)
- No dose adjustment is necessary in kidney disease
- Has not been studied in dialysis patients [15]
- Ticlopidine (Ticlid®)
- Mild kidney disease (CrCl 60 - 89 ml/min): No dose adjustment necessary
- Moderate-to-severe kidney disease: Ticlopidine has not been studied extensively. Manufacturer makes no specific dosage recommendations [18]
- Liver disease dosing
- Clopidogrel (Plavix®)
- No dosage adjustment is necessary in patients with liver disease
- NOTE: Patients with significant liver disease may be at increased risk of bleeding. See coagulopathy of liver disease. [12]
- Prasugrel (Effient®)
- Child-Pugh A/B: No dosage adjustment necessary
- Child-Pugh C: Has not been studied
- NOTE: Patients with significant liver disease may be at increased risk of bleeding. See coagulopathy of liver disease. [12]
- Ticagrelor (Brilinta®)
- No dosage adjustment is necessary in patients with mild liver disease
- Ticagrelor has not been studied in patients with moderate-to-severe liver disease
- Ticagrelor should not be used in severe liver disease
- NOTE: Patients with significant liver disease may be at increased risk of bleeding. See coagulopathy of liver disease. [15]
- Ticlopidine (Ticlid®)
- Ticlopidine should not be used by patients with severe liver disease
- In mild-to-moderate liver disease, drug dose may need to be adjusted
- The manufacturer makes no specific dosage recommendations [18]
- NOTE: Patients with significant liver disease may be at increased risk of bleeding. See coagulopathy of liver disease.
- DRUG INTERACTIONS
- NOTE: Drug interactions presented here are NOT all-inclusive. Other interactions may exist. The interactions presented here are meant to encompass commonly prescribed medications and/or interactions that are well-documented. Always consult your physician or pharmacist before taking medications concurrently. CLICK HERE for more information on drug interactions.
- All P2Y12 Inhibitors
- Drugs that slow gastric emptying (e.g. opiates, GLP-1 analogs) - drugs that slow gastric emptying may delay the absorption of P2Y12 inhibitors. Consider parenteral antiplatelet agents in acute coronary syndrome.
- Drugs that increase the risk of bleeding - drugs that inhibit coagulation may increase the risk of bleeding when taken with P2Y12 inhibitors
- Drugs that may increase the risk of bleeding include:
- Clopidogrel (Plavix®)
- Bupropion (Wellbutrin®) - clopidogrel inhibits CYP2B6 which can lead to elevated bupropion levels. When taken together, doses of bupropion may need to be decreased.
- CYP2C19 inhibitors - see clopidogrel and CYP2C19 below
- CYP2C19 inducers - inducers of CYP2C19 may increase exposure to the active metabolite of clopidogrel and increase the risk of bleeding. Clopidogrel should not be given with CYP2C19 strong inducers (e.g. rifampin) and caution should be used when combining with other inducers.
- CYP2C8 substrates - the acyl-β-glucuronide metabolite of clopidogrel is a CYP2C8 strong inhibitor. Clopidogrel may increase exposure to CYP2C8 substrates.
- Omeprazole (Prilosec®) and esomeprazole (Nexium®) - DO NOT COMBINE with clopidogrel. See clopidogrel and PPIs below
- Repaglinide (Prandin®) - repaglinide is a sensitive CYP2C8 substrate. Clopidogrel increases repaglinide exposure by 4 - 5 fold. Repaglinide should not be given with clopidogrel. If concomitant use cannot be avoided, initiate repaglinide at a dose of 0.5 mg before each meal and titrate based on blood sugars. Do not exceed 4 mg/day. When clopidogrel is added to repaglinide, repaglinide doses should be reduced to no more than 4 mg/day.
- Ticagrelor (Brilinta®)
- Aspirin - in the management of patients with ACS, the use of ticagrelor with maintenance doses of aspirin > 100 mg/day decreased the effectiveness of ticagrelor. Aspirin maintenance doses should be 75 - 100 mg/day when taken with ticagrelor.
- CYP3A strong inhibitors and inducers - ticagrelor should not be taken with strong CYP3A4 inhibitors or inducers
- Digoxin - ticagrelor may increase digoxin levels. Monitor levels when starting concurrent therapy.
- Lovastatin (Mevacor®) - ticagrelor may cause higher blood levels of lovastatin. The manufacturer recommends the lovastatin dose not exceed 40 mg when taken with Ticagrelor
- Simvastatin (Zocor®) - ticagrelor may cause higher blood levels of simvastatin. The manufacturer recommends the simvastatin dose not exceed 40 mg when taken with Ticagrelor
- Ticlopidine (Ticlid®)
- Bupropion (Wellbutrin®) - ticlopidine inhibits CYP2B6 which can lead to elevated bupropion levels. When taken together, doses of bupropion may need to be decreased.
- Phenytoin (Dilantin®) - ticlopidine may raise phenytoin levels. Monitor levels when starting concurrent therapy.
| Metabolism and clearance | ||||
|---|---|---|---|---|
| Enzyme | Clopidogrel | Prasugrel | Ticagrelor | Ticlopidine |
| CYP1A2 | Substrate | - | - | Weak inhibitor |
| CYP2B6 | Substrate Weak inhibitor |
Substrate (primary) Weak inhibitor |
- | Weak inhibitor |
| CYP2C8 | Strong inhibitor | - | - | - |
| CYP2C19 | Substrate (primary) | Substrate | - | Strong inhibitor |
| CYP2C9 | Substrate | Substrate | - | - |
| CYP2D6 | - | - | - | Inhibitor |
| CYP3A4 | Substrate | Substrate (primary) | Substrate (primary) | - |
| P-glycoprotein | - | - | Weak substrate Inhibitor |
- |
- PRICE ($) INFO
Pricing legend
- $ = 0 - $50
- $$ = $51 - $100
- $$$ = $101 - $150
- $$$$ = > $150
- Pricing based on one month of therapy at standard dosing in an adult
- Pricing based on information from GoodRX.com®
- Pricing may vary by region and availability
- BIBLIOGRAPHY
- 1 - Manufacturer's Package Insert for each drug listed
- 2 - PMID 22315266 - Perioperative Management of Antithrombotic Therapy; Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (2012)