Effient

Dosage Forms & Strengths

tablet

• 5mg
• 10mg

Acute Coronary Syndrome

Reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with acute coronary syndrome (ACS) managed by means of percutaneous coronary intervention (PCI) who have either (a) unstable angina or non-ST-elevation MI (NSTEMI) or (b) ST-elevation MI (STEMI) when managed with primary or delayed PCI 

60 mg PO once as loading dose, then 10 mg/day PO in combination with aspirin 81-325 mg/day; if patient <60 kg, consider 5 mg/day PO because of potentially increased bleeding risk (efficacy and safety not established)

Dosing Modifications

Renal impairment

• Dose adjustment not necessary

Hepatic impairment

• Mild-to-moderate: Dose adjustment not necessary
• Severe: Not studied

Sickle Cell Disease (Orphan)

Orphan designation for treatment of sickle cell disease

Sponsor

• Eli Lilly; Lilly Corporate Center; Indianapolis, IN 46285

Not recommended

Acute Coronary Syndrome

<75 years

60 mg PO once as loading dose, then 10 mg/day PO in combination with aspirin 81-325 mg/day

Weight <60 kg: consider 5 mg/day because of potentially increased bleeding risk (efficacy and safety not established)

≥75 years

Generally not recommended, because of increased risk of fatal and intracranial bleeding and uncertain benefit, except in high-risk patients (diabetes or prior MI), for whom effect appears to be greater and use may be considered

1-10%

Bleeding

Anemia

Atrial fibrillation

Back pain

Bradycardia

Dizziness

Dyspnea

Headache

Hypertension

Nausea

<1%

Thrombotic thrombocytopenic purpura

Abnormal hepatic function

Angioedema

Hematoma

Hemolysis

Hemorrhage

Abnormal liver function

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Dosage Forms And Strengths

Effient 5-mg is available as a yellow, elongated hexagonal, film-coated, non-scored tablet debossed with “5121” on one side and 3 parallel arched lines followed by a “5” on the other side.

Effient 10-mg is available as a beige, elongated hexagonal, film-coated, non-scored tablet debossed with “5123” on one side and 3 parallel arched lines followed by a “10” on the other side.

Effient (prasugrel) is available as elongated hexagonal, film-coated, non-scored tablets in the following strengths, colors, imprints, and presentations:

Storage And Handling

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP controlled room temperature]. Dispense and keep product in original container. Keep container closed and do not remove desiccant from bottle. Do not break the tablet.

Manufactured by Eli Lilly and Company, Indianapolis, IN, 46285, USAMarketed by Daiichi Sankyo, Inc. and Lilly USA, LLC. Revised: July 2016

Tell all of your doctors and dentists that you are taking Effient. They should talk to the doctor who prescribed Effient for you, before you have any surgery or invasive procedure.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Certain medicines may increase your risk of bleeding. 

Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist when you get a new medicine.

Effient may not be right for you. Tell your doctor about all of your medical conditions, including if you:

• have any bleeding problems
• have had a stroke or “mini-stroke” (also known as transient ischemic attack or TIA)
• are allergic to any medicines, including clopidogrel (Plavix) or ticlopidine (Ticlid)
• have a history of stomach ulcers, colon polyps, diverticulosis
• have liver problems
• have had any recent severe injury or surgery
• plan to have surgery or a dental procedure. 
• pregnant, or are planning to get pregnant. It is not known if Effient will harm your baby.
• if you are breastfeeding. It is not known if Effient passes into your breastmilk. You and your doctor should decide if you will take Effient or breastfeed. You should not do both without talking with your doctor.

Tell all of your doctors and dentists that you are taking Effient. They should talk to the doctor who prescribed Effient for you, before you have any surgery or invasive procedure.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

Tell your doctor if you are breastfeeding. It is not known if Effient passes into your breastmilk. You and your doctor should decide if you will take Effient or breastfeed. You should not do both without talking with your doctor.

• Keep Effient at room temperature between 59°F to 86°F (15°C to 30°C).
• Keep Effient in the container it comes in.
• Keep the container closed tightly with the gray cylinder inside.
• Protect Effient from moisture.

Keep Effient and all medicines out of the reach of children.

Prasugrel keeps the platelets in your blood from coagulating (clotting) to prevent unwanted blood clots that can occur with certain heart or blood vessel conditions.

Prasugrel is used to prevent blood clots in people with acute coronary syndrome who are undergoing a procedure after a recent heart attack or stroke, and in people with certain disorders of the heart or blood vessels.

Prasugrel may also be used for other purposes not listed in this medication guide.

Do not use this medication if you are allergic to prasugrel, or if you have any active bleeding such as a stomach ulcer or bleeding in the brain (such as from a head injury), or a history of stroke, including TIA ("mini-stroke").

If you have any of these other conditions, you may need a dose adjustment or special tests to safely take this medication:

• a bleeding or blood clotting disorder, such as hemophilia;
• a stomach ulcer;
• severe liver disease; or
• just before or after heart bypass surgery (coronary artery bypass graft, or CABG).

FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether prasugrel passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

General

• It is generally recommended that antiplatelet agents be administered promptly upon presentation or diagnosis in patients with ACS.1 2 993

• Pretreatment with prasugrel may be considered prior to determining coronary anatomy in patients who are not likely to undergo CABG surgery; weigh benefits of pretreatment against risk of surgical bleeding in patients who may require urgent CABG.1 Temporarily discontinue prasugrel at least 7 days prior to CABG, if possible.1

• In patients with STEMI who will undergo primary PCI, ACC and AHA currently recommend administration of the loading dose of prasugrel as early as possible before PCI or at the time of the procedure.70

Administration

Oral Administration

Administer orally without regard to meals.1

Dosage

Available as prasugrel hydrochloride; dosage expressed in terms of prasugrel.1

Adults

60-mg initial loading dose followed by maintenance dosage of 10 mg daily; give in conjunction with aspirin (75–325 mg daily).1

ACC and AHA recommend administering loading dose as soon as possible in patients with STEMI undergoing primary PCI.70 In patients with STEMI undergoing nonprimary/delayed PCI who have not received thrombolytic therapy and in whom coronary anatomy has been determined and PCI is planned, ACC and AHA recommend administering loading dose of prasugrel promptly and no later than 1 hour after PCI.70 Majority of patients in pivotal efficacy study (TRITON-TIMI 38) received loading dose after first coronary guidewire was placed or within 1 hour of PCI.1 2 3

Consider reduced maintenance dosage in patients weighing <60 kg.1 6 18 (See Low Body Weight under Dosage and Administration: Special Populations.)

Optimum duration of maintenance therapy not known; premature discontinuance of antiplatelet therapy in patients with intracoronary stents associated with thrombotic events, sometimes fatal.1 43 44 45 46 47 48 49 54 70 (See Discontinuance of Therapy under Cautions.) Therefore, experts recommend administering prasugrel for at least 12 months in those undergoing PCI with stent placement unless bleeding risk outweighs anticipated benefit; continue aspirin therapy indefinitely.992 993 994 1010

Special Populations

Hepatic Impairment

No dosage adjustments required in patients with mild to moderate hepatic impairment (Child-Pugh class A or B).1 Not studied in patients with severe hepatic disease.1

Renal Impairment

No dosage adjustments required.1

Low Body Weight

May reduce maintenance dosage to 5 mg daily in patients who weigh <60 kg, although safety and efficacy of such lower dosages not established.1 6 18 (See Bleeding under Cautions.)

Metabolized principally by CYP3A4 and CYP2B6; to a lesser extent by CYP2C9 and CYP2C19.1 13 14 22 23 30 Not likely to inhibit CYP isoenzymes 1A2, 2C9, 2C19, 2D6 or 3A4 nor induce isoenzymes 1A2 or 3A4.1 13 Weak inhibitor of CYP2B6.1 25

Does not inhibit P-glycoprotein (Pgp) transport system.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Clinically important interactions mediated by CYP enzymes unlikely.1 13 25

CYP3A4 inhibitors: No substantial effect on systemic exposure or antiplatelet activity of prasugrel’s active metabolite.1 22

CYP3A4 inducers: Not expected to substantially alter pharmacokinetic or pharmacodynamic response to prasugrel.1 25

Drugs metabolized by CYP2B6: Potential for increased plasma concentrations and exposure to concomitantly administered drug; however, clinically important interactions not expected because of weak inhibition of CYP2B6.1 25

Other Antiplatelet or Antithrombotic Agents

Manufacturer states that prasugrel may be administered concomitantly with aspirin, heparin, and GP IIb/IIIa-receptor inhibitors.1 While evidence from drug interaction studies with other antiplatelet or antithrombotic agents generally is lacking, increased risk of bleeding likely with concomitant use of such agents.13 14

Specific Drugs or Foods

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

In the U.S.

• Effient

Available Dosage Forms:

• Tablet

Therapeutic Class: Platelet Aggregation Inhibitor

Pharmacologic Class: ADP-Induced Aggregation Inhibitor

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it. Blood and urine tests may be needed to check for unwanted effects.

Tell all of your medical doctors, dentists, and nurses that you are taking this medicine. Prasugrel may increase the risk of serious bleeding during an operation or some dental procedures. Treatment may have to be stopped about 7 days before the operation or dental procedure.

Check with your doctor right away if you have the following symptoms: change in mental status, dark or bloody urine, difficulty with speaking, fever, pale color of the skin, pinpoint red spots on the skin, seizures, weakness, yellow eyes or skin. These may be symptoms of a serious condition called thrombotic thrombocytopenic purpura (TTP).

This medicine may cause serious allergic reactions, including angioedema. Angioedema can be life-threatening and requires immediate medical attention. Tell your doctor right away if you have chest pain, a rash, itching, swelling of the face, lips, tongue, or throat, or trouble with swallowing or breathing while you are using the medicine.

Do not stop taking this medicine without checking with your doctor first. To do so may increase your risk for clots.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

The following serious adverse reactions are also discussed elsewhere in the labeling:

• Bleeding [see Boxed Warning and Warnings and Precautions (5.1, 5.2)]
• Thrombotic Thrombocytopenic Purpura [see Warnings and Precautions (5.4)]
• Hypersensitivity Including Angioedema [see Warnings and Precautions (5.5)]

Clinical Trials Experience

Safety in patients with ACS undergoing PCI was evaluated in a clopidogrel-controlled study, TRITON-TIMI 38, in which 6741 patients were treated with Effient (60-mg loading dose and 10-mg once daily) for a median of 14.5 months (5802 patients were treated for over 6 months; 4136 patients were treated for more than 1 year). The population treated with Effient was 27 to 96 years of age, 25% female, and 92% Caucasian. All patients in the TRITON-TIMI 38 study were to receive aspirin. The dose of clopidogrel in this study was a 300-mg loading dose and 75-mg once daily.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials cannot be directly compared with the rates observed in other clinical trials of another drug and may not reflect the rates observed in practice.

Drug Discontinuation

The rate of study drug discontinuation because of adverse reactions was 7.2% for Effient and 6.3% for clopidogrel. Bleeding was the most common adverse reaction leading to study drug discontinuation for both drugs (2.5% for Effient and 1.4% for clopidogrel).

Bleeding

Bleeding Unrelated to CABG Surgery - In TRITON-TIMI 38, overall rates of TIMI Major or Minor bleeding adverse reactions unrelated to coronary artery bypass graft surgery (CABG) were significantly higher on Effient than on clopidogrel, as shown in Table 1.

Figure 1 demonstrates non-CABG related TIMI Major or Minor bleeding. The bleeding rate is highest initially, as shown in Figure 1 (inset: Days 0 to 7) [see Warnings and Precautions (5.1)].

Bleeding by Weight and Age - In TRITON-TIMI 38, non-CABG-related TIMI Major or Minor bleeding rates in patients with the risk factors of age ≥75 years and weight <60 kg are shown in Table 2.

Bleeding Related to CABG - In TRITON-TIMI 38, 437 patients who received a thienopyridine underwent CABG during the course of the study. The rate of CABG-related TIMI Major or Minor bleeding was 14.1% for the Effient group and 4.5% in the clopidogrel group (see Table 3). The higher risk for bleeding adverse reactions in patients treated with Effient persisted up to 7 days from the most recent dose of study drug.

Bleeding Reported as Adverse Reactions - Hemorrhagic events reported as adverse reactions in TRITON-TIMI 38 were, for Effient and clopidogrel, respectively: epistaxis (6.2%, 3.3%), gastrointestinal hemorrhage (1.5%, 1.0%), hemoptysis (0.6%, 0.5%), subcutaneous hematoma (0.5%, 0.2%), post-procedural hemorrhage (0.5%, 0.2%), retroperitoneal hemorrhage (0.3%, 0.2%), pericardial effusion/hemorrhage/tamponade (0.3%, 0.2%), and retinal hemorrhage (0.0%, 0.1%).

Malignancies

During TRITON-TIMI 38, newly-diagnosed malignancies were reported in 1.6% and 1.2% of patients treated with prasugrel and clopidogrel, respectively. The sites contributing to the differences were primarily colon and lung. In another Phase 3 clinical study of ACS patients not undergoing PCI, in which data for malignancies were prospectively collected, newly-diagnosed malignancies were reported in 1.8% and 1.7% of patients treated with prasugrel and clopidogrel, respectively. The site of malignancies was balanced between treatment groups except for colorectal malignancies. The rates of colorectal malignancies were 0.3% prasugrel, 0.1% clopidogrel and most were detected during investigation of GI bleed or anemia. It is unclear if these observations are causally-related, are the result of increased detection because of bleeding, or are random occurrences.

Other Adverse Events

In TRITON-TIMI 38, common and other important non-hemorrhagic adverse events were, for Effient and clopidogrel, respectively: severe thrombocytopenia (0.06%, 0.04%), anemia (2.2%, 2.0%), abnormal hepatic function (0.22%, 0.27%), allergic reactions (0.36%, 0.36%), and angioedema (0.06%, 0.04%). Table 4 summarizes the adverse events reported by at least 2.5% of patients.

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) [see Warnings and Precautions (5.4) and Patient Counseling Information (17)]

Immune system disorders Hypersensitivity reactions including anaphylaxis [see Contraindications (4.3)]

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.

You should not use Effient if you are allergic to prasugrel, or if you have:

• any active bleeding such as a stomach ulcer or bleeding in the brain (such as from a head injury);

• a history of stroke, including TIA ("mini-stroke"); or

• if you are scheduled to have surgery, especially heart bypass surgery (coronary artery bypass graft, or CABG).

To make sure Effient is safe for you, tell your doctor if you have:

• a stomach ulcer;

• stomach or intestinal bleeding;

• a history of surgery, injury, or medical emergency;

• liver or kidney disease;

• if you weigh less than 132 pounds;

• if you also use other medicines to treat or prevent blood clots; or

• if you have ever had a severe allergic reaction to clopidogrel (Plavix) or ticlopidine (Ticlid).

Effient is not expected to be harmful to an unborn baby. However, aspirin is usually given with Effient, and aspirin can cause bleeding when it is taken during the last 3 months of pregnancy. Aspirin can also cause side effects in a newborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether prasugrel passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Take Effient exactly as it was prescribed for you. Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Effient is usually given together with aspirin. Follow your doctor's instructions about how much aspirin to take and for how long.

Effient can be taken with or without food.

Because prasugrel keeps your blood from coagulating (clotting) to prevent unwanted blood clots, Effient can also make it easier for you to bleed, even from a minor injury such as a fall or a bump on the head. Contact your doctor or seek emergency medical attention if you fall or hit your head, or have any bleeding that will not stop.

If you need surgery or dental work, tell the surgeon or dentist ahead of time that you are using Effient. You may need to stop using the medicine for a short time before surgery to prevent excessive bleeding.

Do not stop taking Effient unless your doctor tells you to. If you stop taking this medicine too soon you could have life-threatening medical problems such as a blood clot or a heart attack.

Store at room temperature away from moisture and heat. Keep the tablets in their original container, along with the packet or canister of moisture-absorbing preservative. Keep the bottle tightly closed when not in use.