Effient Drug Information
Generic name: PRASUGREL HYDROCHLORIDE
Uses of Effient
Acute Coronary Syndrome Effient ® is indicated to reduce the rate of thrombotic CV events (including stent thrombosis) in patients with acute coronary syndrome (ACS) who are to be managed with percutaneous coronary intervention (PCI) as follows: Patients with unstable angina (UA) or non-ST-elevation myocardial infarction (NSTEMI). Patients with ST-elevation myocardial infarction (STEMI) when managed with primary or delayed PCI. Effient has been shown to reduce the rate of a combined endpoint of cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke compared to clopidogrel.
The difference between treatments was driven predominantly by MI, with no difference on strokes and little difference on CV death.
Dosage & Administration of Effient
Initiate Effient treatment as a single 60 mg oral loading dose and then continue at 10 mg orally once daily. Patients taking Effient should also take aspirin (75 mg to 325 mg) daily. Effient may be administered with or without food.
Continue at 10 mg once daily with or without food. Consider 5 mg once daily for patients <60 kg. Timing of Loading Dose In the clinical trial that established the efficacy and safety of Effient, the loading dose of Effient was not administered until coronary anatomy was established in UA/NSTEMI patients and in STEMI patients presenting more than 12 hours after symptom onset.
In STEMI patients presenting within 12 hours of symptom onset, the loading dose of Effient was administered at the time of diagnosis, although most received Effient at the time of PCI. For the small fraction of patients that required urgent CABG after treatment with Effient, the risk of significant bleeding was substantial. Although it is generally recommended that antiplatelet therapy be administered promptly in the management of ACS because many cardiovascular events occur within hours of initial presentation, in a trial of 4033 NSTEMI patients, no clear benefit was observed when Effient loading dose was administered prior to diagnostic coronary angiography compared to at the time of PCI; however, risk of bleeding was increased with early administration in patients undergoing PCI or early CABG.
Dosing in Low Weight Patients Compared to patients weighing ≥60 kg, patients weighing <60 kg have an increased exposure to the active metabolite of prasugrel and an increased risk of bleeding on a 10 mg once daily maintenance dose. Consider lowering the maintenance dose to 5 mg in patients <60 kg. The effectiveness and safety of the 5 mg dose have not been prospectively studied.
Side Effects of Effient
Postmarketing Experience
The following adverse reactions have been identified during post-approval use of Effient. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and lymphatic system disorders — thrombocytopenia, thrombotic thrombocytopenic purpura (TTP) Immune system disorders — hypersensitivity reactions including anaphylaxis
| Effient (%) (N=6741) | Clopidogrel (%) (N=6716) | |
|---|---|---|
| TIMI Major or Minor bleeding | 4.5 | 3.4 |
| TIMI Major bleeding See 5.1 for definition. | 2.2 | 1.7 |
| Life-threatening | 1.3 | 0.8 |
| Fatal | 0.3 | 0.1 |
| Symptomatic intracranial hemorrhage (ICH) | 0.3 | 0.3 |
| Requiring inotropes | 0.3 | 0.1 |
| Requiring surgical intervention | 0.3 | 0.3 |
| Requiring transfusion (≥4 units) | 0.7 | 0.5 |
| TIMI Minor bleeding | 2.4 | 1.9 |
| Major/Minor | Fatal | |||
|---|---|---|---|---|
| Effient 10 mg Effient maintenance dose (%) | Clopidogrel 75 mg clopidogrel maintenance dose (%) | Effient (%) | Clopidogrel (%) | |
| Weight <60 kg (N=308 Effient, N=356 clopidogrel) | 10.1 | 6.5 | 0.0 | 0.3 |
| Weight ≥60 kg (N=6373 Effient, N=6299 clopidogrel) | 4.2 | 3.3 | 0.3 | 0.1 |
| Age <75 years (N=5850 Effient, N=5822 clopidogrel) | 3.8 | 2.9 | 0.2 | 0.1 |
| Age ≥75 years (N=891 Effient, N=894 clopidogrel) | 9.0 | 6.9 | 1.0 | 0.1 |
| Effient (%) (N=213) | Clopidogrel (%) (N=224) | |
|---|---|---|
| TIMI Major or Minor bleeding | 14.1 | 4.5 |
| TIMI Major bleeding | 11.3 | 3.6 |
| Fatal | 0.9 | 0 |
| Reoperation | 3.8 | 0.5 |
| Transfusion of ≥5 units | 6.6 | 2.2 |
| Intracranial hemorrhage | 0 | 0 |
| TIMI Minor bleeding | 2.8 | 0.9 |
| Effient (%) (N=6741) | Clopidogrel (%) (N=6716) | |
|---|---|---|
| Hypertension | 7.5 | 7.1 |
| Hypercholesterolemia/Hyperlipidemia | 7.0 | 7.4 |
| Headache | 5.5 | 5.3 |
| Back pain | 5.0 | 4.5 |
| Dyspnea | 4.9 | 4.5 |
| Nausea | 4.6 | 4.3 |
| Dizziness | 4.1 | 4.6 |
| Cough | 3.9 | 4.1 |
| Hypotension | 3.9 | 3.8 |
| Fatigue | 3.7 | 4.8 |
| Noncardiac chest pain | 3.1 | 3.5 |
| Atrial fibrillation | 2.9 | 3.1 |
| Bradycardia | 2.9 | 2.4 |
| Leukopenia (<4 × 10 9 WBC WBC = white blood cell /L) | 2.8 | 3.5 |
| Rash | 2.8 | 2.4 |
| Pyrexia | 2.7 | 2.2 |
| Peripheral edema | 2.7 | 3.0 |
| Pain in extremity | 2.6 | 2.6 |
| Diarrhea | 2.3 | 2.6 |
Warnings & Cautions for Effient
General Risk of Bleeding
Thienopyridines, including Effient, increase the risk of bleeding. With the dosing regimens used in TRITON-TIMI 38, TIMI (Thrombolysis in Myocardial Infarction) Major (clinically overt bleeding associated with a fall in hemoglobin ≥5 g/dL, or intracranial hemorrhage) and TIMI Minor (overt bleeding associated with a fall in hemoglobin of ≥3 g/dL but <5 g/dL), bleeding events were more common on Effient than on clopidogrel. The bleeding risk is highest initially, as shown in Figure 1 (events through 450 days; inset shows events through 7 days).
Figure 1: Non-CABG-Related TIMI Major or Minor Bleeding Events Suspect bleeding in any patient who is hypotensive and has recently undergone coronary angiography, PCI, CABG, or other surgical procedures even if the patient does not have overt signs of bleeding. Do not use Effient in patients with active bleeding, prior TIA or stroke. Other risk factors for bleeding are: Age ≥75 years.
Because of the risk of bleeding (including fatal bleeding) and uncertain effectiveness in patients ≥75 years of age, use of Effient is generally not recommended in these patients, except in high-risk situations (patients with diabetes or history of myocardial infarction) where its effect appears to be greater and its use may be considered. CABG or other surgical procedure. Body weight <60 kg.
Consider a lower (5 mg) maintenance dose. Propensity to bleed (e.g., recent trauma, recent surgery, recent or recurrent gastrointestinal (GI) bleeding, active peptic ulcer disease, severe hepatic impairment, or moderate to severe renal impairment). Medications that increase the risk of bleeding (e.g., oral anticoagulants, chronic use of nonsteroidal anti-inflammatory drugs, and fibrinolytic agents).
Aspirin and heparin were commonly used in TRITON-TIMI 38. Thienopyridines inhibit platelet aggregation for the lifetime of the platelet (7-10 days), so withholding a dose will not be useful in managing a bleeding event or the risk of bleeding associated with an invasive procedure. Because the half-life of prasugrel's active metabolite is short relative to the lifetime of the platelet, it may be possible to restore hemostasis by administering exogenous platelets; however, platelet transfusions within 6 hours of the loading dose or 4 hours of the maintenance dose may be less effective.
Figure 1
Coronary Artery Bypass Graft Surgery-Related Bleeding
The risk of bleeding is increased in patients receiving Effient who undergo CABG. If possible, Effient should be discontinued at least 7 days prior to CABG. The higher risk for bleeding events in patients treated with Effient persisted up to 7 days from the most recent dose of study drug.
Do not start Effient in patients likely to undergo urgent CABG. CABG-related bleeding may be treated with transfusion of blood products, including packed red blood cells and platelets; however, platelet transfusions within 6 hours of the loading dose or 4 hours of the maintenance dose may be less effective.
Discontinuation of Effient
Discontinue thienopyridines, including Effient, for active bleeding, elective surgery, stroke, or TIA. The optimal duration of thienopyridine therapy is unknown. In patients who are managed with PCI and stent placement, premature discontinuation of any antiplatelet medication, including thienopyridines, conveys an increased risk of stent thrombosis, myocardial infarction, and death.
Patients who require premature discontinuation of a thienopyridine will be at increased risk for cardiac events. Lapses in therapy should be avoided, and if thienopyridines must be temporarily discontinued because of an adverse event(s), they should be restarted as soon as possible.
Thrombotic Thrombocytopenic Purpura (TTP) TTP has been reported with the use of Effient. TTP can occur after a brief exposure (<2 weeks). TTP is a serious condition that can be fatal and requires urgent treatment, including plasmapheresis (plasma exchange).
TTP is characterized by thrombocytopenia, microangiopathic hemolytic anemia (schistocytes seen on peripheral smear), neurological findings, renal dysfunction, and fever.
Hypersensitivity Including Angioedema
Hypersensitivity including angioedema has been reported in patients receiving Effient, including patients with a history of hypersensitivity reaction to other thienopyridines.
Drug Interactions with Effient
Warfarin Coadministration of Effient and warfarin increases the risk of bleeding.
Nonsteroidal Anti-Inflammatory Drugs Coadministration of Effient and NSAIDs (used chronically) may increase the risk of bleeding.
Opioids As with other oral P2Y 12 inhibitors, coadministration of opioid agonists delay and reduce the absorption of prasugrel's active metabolite presumably because of slowed gastric emptying. Consider the use of a parenteral anti-platelet agent in acute coronary syndrome patients requiring coadministration of morphine or other opioid agonists.
Other Concomitant Medications Effient can be administered with drugs that are inducers or inhibitors of cytochrome P450 enzymes. Effient can be administered with aspirin (75 mg to 325 mg per day), heparin, GPIIb/IIIa inhibitors, statins, digoxin, and drugs that elevate gastric pH, including proton pump inhibitors and H 2 blockers.
Pregnancy Safety for Effient
Pregnancy Risk Summary There are no data with Effient use in pregnant women to inform a drug-associated risk. No structural malformations were observed in animal reproductive and developmental toxicology studies when rats and rabbits were administered prasugrel during organogenesis at doses of up to 30 times the recommended therapeutic exposures in humans. Due to the mechanism of action of Effient, and the associated identified risk of bleeding, consider the benefits and risks of Effient and possible risks to the fetus when prescribing Effient to a pregnant woman.
The background risk of major birth defects and miscarriage for the indicated population is unknown. The background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies. Data Animal Data In embryo-fetal developmental toxicology studies, pregnant rats and rabbits received prasugrel at maternally toxic oral doses equivalent to more than 40 times the human exposure.
A slight decrease in fetal body weight was observed, but there were no structural malformations in either species. In prenatal and postnatal rat studies, maternal treatment with prasugrel had no effect on the behavioral or reproductive development of the offspring at doses greater than 150 times the human exposure.
Pediatric Use of Effient
Pediatric Use Safety and effectiveness in pediatric patients have not been established. In a randomized, placebo-controlled trial, the primary objective of reducing the rate of vaso-occlusive crisis (painful crisis or acute chest syndrome) in pediatric patients, aged 2 to less than 18 years, with sickle cell anemia was not met.
Contraindications for Effient
Active Bleeding Effient is contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage (ICH).
Prior Transient Ischemic Attack or Stroke Effient is contraindicated in patients with a history of prior transient ischemic attack (TIA) or stroke. In TRITON-TIMI 38 ( TR ial to Assess I mprovement in T herapeutic Outcomes by O ptimizing Platelet Inhibitio N with Prasugrel), patients with a history of TIA or ischemic stroke (>3 months prior to enrollment) had a higher rate of stroke on Effient (6.5%; of which 4.2% were thrombotic stroke and 2.3% were intracranial hemorrhage ) than on clopidogrel (1.2%; all thrombotic). Patients with a history of ischemic stroke within 3 months of screening and patients with a history of hemorrhagic stroke at any time were excluded from TRITON-TIMI 38.
Patients who experience a stroke or TIA while on Effient generally should have therapy discontinued.
Hypersensitivity Effient is contraindicated in patients with hypersensitivity (e.g., anaphylaxis) to prasugrel or any component of the product.
Overdosage Information for Effient
Signs and Symptoms
Platelet inhibition by prasugrel is rapid and irreversible, lasting for the life of the platelet, and is unlikely to be increased in the event of an overdose. In rats, lethality was observed after administration of 2000 mg/kg. Symptoms of acute toxicity in dogs included emesis, increased serum alkaline phosphatase, and hepatocellular atrophy.
Symptoms of acute toxicity in rats included mydriasis, irregular respiration, decreased locomotor activity, ptosis, staggering gait, and lacrimation.
Recommendations about Specific Treatment
Platelet transfusion may restore clotting ability. The prasugrel active metabolite is not likely to be removed by dialysis.
Clinical Studies of Effient
The clinical evidence for the effectiveness of Effient is derived from the TRITON-TIMI 38 ( TR ial to Assess I mprovement in T herapeutic Outcomes by O ptimizing Platelet Inhibitio N with Prasugrel) study, a 13,608 patient, multicenter, international, randomized, double-blind, parallel-group study comparing Effient to a regimen of clopidogrel, each added to aspirin and other standard therapy, in patients with ACS (UA, NSTEMI, or STEMI) who were to be managed with PCI. Randomization was stratified for UA/NSTEMI and STEMI. Patients with UA/NSTEMI presenting within 72 hours of symptom onset were to be randomized after undergoing coronary angiography.
Patients with STEMI presenting within 12 hours of symptom onset could be randomized prior to coronary angiography. Patients with STEMI presenting between 12 hours and 14 days of symptom onset were to be randomized after undergoing coronary angiography. Patients underwent PCI, and for both UA/NSTEMI and STEMI patients, the loading dose was to be administered anytime between randomization and 1 hour after the patient left the catheterization lab.
If patients with STEMI were treated with thrombolytic therapy, randomization could not occur until at least 24 hours (for tenecteplase, reteplase, or alteplase) or 48 hours (for streptokinase) after the thrombolytic was given. Patients also received aspirin (75 mg to 325 mg once daily). Other therapies, such as heparin and intravenous glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors, were administered at the discretion of the treating physician.
Oral anticoagulants, other platelet inhibitors, and chronic NSAIDs were not allowed. The primary outcome measure was the composite of cardiovascular death, nonfatal MI, or nonfatal stroke in the UA/NSTEMI population. Success in this group allowed analysis of the same endpoint in the overall ACS and STEMI populations.
Nonfatal MIs included both MIs detected solely through analysis of creatine kinase muscle-brain (CK-MB) changes and clinically apparent (investigator-reported) MIs. The median time from symptom onset to study drug administration was 7 hours for patients with STEMI and 30 hours for patients with UA/NSTEMI. Approximately 99% of patients underwent PCI.
The study drug was administered after the first coronary guidewire was placed in approximately 75% of patients. Effient significantly reduced total endpoint events compared to clopidogrel (see Figure 3 and Table 5 ). The reduction of total endpoint events was driven primarily by a decrease in nonfatal MIs, both those occurring early (through 3 days) and later (after 3 days).
Approximately 40% of MIs occurred peri-procedurally and were detected solely by changes in CK-MB. Administration of the clopidogrel loading dose in TRITON-TIMI 38 was delayed relative to the placebo-controlled trials that supported its approval for ACS. Effient produced higher rates of clinically significant bleeding than clopidogrel in TRITON-TIMI 38.
Choice of therapy requires balancing these differences in outcome. The treatment effect of Effient was apparent within the first few days, and persisted to the end of the study (see Figure 3 ). The inset shows results over the first 7 days.
Figure 3: Time to First Event of CV Death, MI, or Stroke (TRITON-TIMI 38) The Kaplan-Meier curves (see Figure 3 ) show the primary composite endpoint of CV death, nonfatal MI, or nonfatal stroke over time in the UA/NSTEMI and STEMI populations. In both populations, the curves separate within the first few hours. In the UA/NSTEMI population, the curves continue to diverge throughout the 15-month follow-up period.
In the STEMI population, the early separation was maintained throughout the 15-month follow-up period, but there was no progressive divergence after the first few weeks. Effient reduced the occurrence of the primary composite endpoint compared to clopidogrel in both the UA/NSTEMI and STEMI populations (see Table 5 ). In patients who survived an on-study myocardial infarction, the incidence of subsequent events was also lower in the Effient group.
Results are generally consistent across pre-specified subgroups, with the exception of patients with a history of TIA or stroke. The treatment effect was driven primarily by a reduction in nonfatal MI. The effect in patients ≥75 years of age was also somewhat smaller, and bleeding risk is higher in these individuals.
See below for analyses of patients ≥75 years of age with risk factors. is generally not recommended in patients ≥75 years of age, except in high-risk situations (diabetes mellitus or prior MI) where its effect appears to be greater and its use may be considered. These recommendations are based on subgroup analyses (see Table 6 ) and must be interpreted with caution, but the data suggest that Effient reduces ischemic events in such patients. The difference manifested early and was maintained through one year of follow-up.
Findings were similar with bare metal and drug-eluting stents. In TRITON-TIMI 38, prasugrel reduced ischemic events (mainly nonfatal MIs) and increased bleeding events relative to clopidogrel. The findings are consistent with the intended greater inhibition of platelet aggregation by prasugrel at the doses used in the study.
There is, however, an alternative explanation: both prasugrel and clopidogrel are prodrugs that must be metabolized to their active moieties. Whereas the pharmacokinetics of prasugrel's active metabolite is not known to be affected by genetic variations in CYP2B6, CYP2C9, CYP2C19, or CYP3A5, the pharmacokinetics of clopidogrel's active metabolite is affected by CYP2C19 genotype, and approximately 30% of Caucasians are reduced metabolizers. Moreover, certain proton pump inhibitors, widely used in the ACS patient population and used in TRITON-TIMI 38, inhibit CYP2C19, thereby decreasing formation of clopidogrel's active metabolite.
Thus, reduced-metabolizer status and use of proton pump inhibitors may diminish clopidogrel's activity in a fraction of the population, and may have contributed to prasugrel's greater treatment effect and greater bleeding rate in TRITON-TIMI 38. The extent to which these factors were operational, however, is unknown. Figure 3 Figure 4 Figure 5
| Patients with events | From Kaplan-Meier analysis | |||
|---|---|---|---|---|
| Effient (%) | Clopidogrel (%) | Relative Risk Reduction (%) RRR = (1-Hazard Ratio) × 100%. Values with a negative relative risk reduction indicate a relative risk increase. (95% CI) | p-value | |
| UA/NSTEMI | N=5044 | N=5030 | ||
| CV death, nonfatal MI, or nonfatal stroke | 9.3 | 11.2 | 18.0 (7.3, 27.4) | 0.002 |
| CV death | 1.8 | 1.8 | 2.1 (-30.9, 26.8) | 0.885 |
| Nonfatal MI | 7.1 | 9.2 | 23.9 (12.7, 33.7) | <0.001 |
| Nonfatal Stroke | 0.8 | 0.8 | 2.1 (-51.3, 36.7) | 0.922 |
| STEMI | N=1769 | N=1765 | ||
| CV death, nonfatal MI, or nonfatal stroke | 9.8 | 12.2 | 20.7 (3.2, 35.1) | 0.019 |
| CV death | 2.4 | 3.3 | 26.2 (-9.4, 50.3) | 0.129 |
| Nonfatal MI | 6.7 | 8.8 | 25.4 (5.2, 41.2) | 0.016 |
| Nonfatal Stroke | 1.2 | 1.1 | -9.7 (-104.0, 41.0) | 0.77 |
| Effient | Clopidogrel | Hazard Ratio (95% CI) | |||
|---|---|---|---|---|---|
| N | % with events | N | % with events | ||
| Age ≥75 | |||||
| Diabetes – yes | 249 | 14.9 | 234 | 21.8 | 0.64 (0.42, 0.97) |
| Diabetes – no | 652 | 16.4 | 674 | 15.3 | 1.1 (0.83, 1.43) |
| Age <75 | |||||
| Diabetes – yes | 1327 | 10.8 | 1336 | 14.8 | 0.72 (0.58, 0.89) |
| Diabetes – no | 4585 | 7.8 | 4551 | 9.5 | 0.82 (0.71, 0.94) |
| Age ≥75 | |||||
| Prior MI – yes | 220 | 17.3 | 212 | 22.6 | 0.72 (0.47, 1.09) |
| Prior MI – no | 681 | 15.6 | 696 | 15.2 | 1.05 (0.80, 1.37) |
| Age <75 | |||||
| Prior MI – yes | 1006 | 12.2 | 996 | 15.4 | 0.78 (0.62, 0.99) |
| Prior MI – no | 4906 | 7.7 | 4891 | 9.7 | 0.78 (0.68, 0.90) |
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
Ready to save on Effient?
Compare prescription prices at over 70,000 pharmacies and start saving today—no enrollment required.
Compare Effient Prices