Side effects for eliquis

Eliquis

Generic Name: apixaban (a PIX a ban)
Brand Names: Eliquis

Medically reviewed by Kaci Durbin, MD Last updated on Oct 21, 2019.

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What is Eliquis?

Eliquis (apixaban) blocks the activity of certain clotting substances in the blood.

Eliquis is used to lower the risk of stroke or a blood clot in people with a heart rhythm disorder called atrial fibrillation.

Eliquis is also used to lower the risk of forming a blood clot in the legs and lungs of people who have just had hip or knee replacement surgery.

Eliquis is used to treat blood clots in the veins of your legs (deep vein thrombosis) or lungs (pulmonary embolism), and lower the risk of them occurring again.

Important Information

Eliquis increases your risk of severe or fatal bleeding, especially if you take certain medicines at the same time (including some over-the-counter medicines). It is very important to tell your doctor about all medicines you have recently used.

Call your doctor at once if you have signs of bleeding such as: swelling, pain, feeling very weak or dizzy, bleeding gums, nosebleeds, heavy menstrual periods or abnormal vaginal bleeding, blood in your urine, bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds, or any bleeding that will not stop.

Eliquis should be stopped 24-48 hours prior to any surgery, invasive procedure, or dental work. Tell your surgeon if you are taking Eliquis.

Eliquis can cause a very serious blood clot around your spinal cord if you undergo a spinal tap or receive spinal anesthesia (epidural), especially if you have a genetic spinal defect, if you have a spinal catheter in place, if you have a history of spinal surgery or repeated spinal taps, or if you are also using other drugs that can affect blood clotting. This type of blood clot can lead to long-term or permanent paralysis.

Get emergency medical help if you have symptoms of a spinal cord blood clot such as back pain, numbness or muscle weakness in your lower body, or loss of bladder or bowel control.

Do not stop taking Eliquis unless your doctor tells you to. Stopping suddenly can increase your risk of blood clot or stroke.

Before taking this medicine

You should not take Eliquis if you are allergic to apixaban, or if you have active bleeding from a surgery, injury, or other cause.

Eliquis may cause you to bleed more easily, especially if you have a bleeding disorder that is inherited or caused by disease.

Tell your doctor if you have an artificial heart valve, or if you have ever had:

  • liver or kidney disease (or if you are on dialysis);

  • if you are older than 80; or

  • if you weigh less than 132 pounds (60 kilograms).

Eliquis can cause a very serious blood clot around your spinal cord if you undergo a spinal tap or receive spinal anesthesia (epidural). This type of blood clot could cause long-term paralysis, and may be more likely to occur if:

  • you have a spinal catheter in place or if a catheter has been recently removed;

  • you have a history of spinal surgery or repeated spinal taps;

  • you have recently had a spinal tap or epidural anesthesia;

  • you are taking aspirin or an NSAID (nonsteroidal anti-inflammatory drug) – aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), diclofenac, indomethacin, meloxicam, and others; or

  • you are using other medicines to treat or prevent blood clots.

Taking Eliquis may increase the risk of bleeding while you are pregnant or during your delivery. Tell your doctor if you are pregnant or plan to become pregnant.

You should not breast-feed while using this medicine.

How should I take Eliquis?

Eliquis is usually taken twice per day. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose. Use the medicine exactly as directed.

You may take Eliquis with or without food.

If you cannot swallow a tablet whole, crush and mix it with water, apple juice, or a spoonful of applesauce. Swallow the mixture right away without chewing. Do not save it for later use.

A crushed tablet mixture may also be given through a nasogastric (NG) feeding tube. Read and carefully follow any Instructions for Use provided with your medicine. Ask your doctor or pharmacist if you do not understand these instructions.

Do not stop taking Eliquis unless your doctor tells you to.Stopping suddenly can increase your risk of blood clot or stroke.

If you stop taking Eliquis for any reason, your doctor may prescribe another medication to prevent blood clots until you start taking it again.

Store at room temperature away from moisture and heat.

What happens if I miss a dose?

Take the missed dose on the same day you remember it. Take your next dose at the regular time and stay on your twice-daily schedule. Do not take two doses at one time.

Get your prescription refilled before you run out of medicine completely.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while taking Eliquis?

Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth.

Avoid medications that can increase your risk of bleeding, such as aspirin or NSAIDs (nonsteroidal anti-inflammatory drugs)- ibuprofen (Advil, Motrin), naproxen (Aleve), diclofenac, indomethacin, meloxicam, and others.

Eliquis side effects

Get emergency medical help if you have signs of an allergic reaction to Eliquis: hives; chest pain, wheezing, difficult breathing; feeling light-headed; swelling of your face, lips, tongue, or throat.

Also seek emergency medical attention if you have symptoms of a spinal blood clot: back pain, numbness or muscle weakness in your lower body, or loss of bladder or bowel control.

Call your doctor at once if you have:

  • bleeding (from any area including nose, mouth, vagina, or rectum) that will not stop;

  • headache, dizziness, weakness, feeling like you might pass out;

  • urine that looks red, pink, or brown; or

  • black or bloody stools, coughing up blood or vomit that looks like coffee grounds.

The most common side effects of Eliquis include easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), or bleeding from injection sites.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Eliquis?

Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective.

Many other drugs (including some over-the-counter medicines) can increase your risk of bleeding or blood clots, or your risk of developing blood clots around the brain or spinal cord during a spinal tap or epidural. It is very important to tell your doctor about all medicines you have recently used, especially:

  • any other medicines to treat or prevent blood clots;

  • a blood thinner such as heparin or warfarin (Coumadin, Jantoven);

  • an antidepressant (including selective serotonin reuptake inhibitors or SSRI drugs); or

  • an NSAID (nonsteroidal anti-inflammatory drug) used long term.

This list is not complete and many other drugs may interact with apixaban. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Eliquis only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2020 Cerner Multum, Inc. Version: 4.01.

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More about Eliquis (apixaban)

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U.S. FDA Approves ELIQUIS® (apixaban) to Reduce the Risk of Stroke and Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation

PRINCETON, N.J. & NEW YORK–(BUSINESS WIRE)–Bristol-Myers Squibb Company (NYSE: BMY) and Pfizer Inc. (NYSE: PFE) announced that the U.S. Food and Drug Administration (FDA) approved ELIQUIS® (apixaban) to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Atrial fibrillation, the most common type of irregular heartbeat, affects approximately 5.8 million people in the U.S., and results in a five times greater risk of stroke. In the U.S., 15 percent of strokes are attributable to atrial fibrillation.

“The approval of ELIQUIS offers patients with nonvalvular atrial fibrillation a novel treatment option for reducing the risk of stroke,” said Lamberto Andreotti, chief executive officer, Bristol-Myers Squibb. “ELIQUIS is the result of leading scientific innovation and the shared vision of our alliance to introduce a new oral anticoagulant for patients with nonvalvular atrial fibrillation in the U.S.”

Ian Read, chairman and chief executive officer, Pfizer Inc. said, “The profile of ELIQUIS, combined with the strong legacy and complementary capabilities that Pfizer and Bristol-Myers Squibb have in the cardiovascular space, positions us well to deliver this important new treatment option to patients and health care professionals.”

The ELIQUIS clinical trial program is the largest completed clinical development program designed to evaluate risk reduction of stroke or systemic embolism in nonvalvular atrial fibrillation patients; it included two landmark Phase 3 studies — ARISTOTLE and AVERROES — in patients with nonvalvular atrial fibrillation and at least one additional risk factor for stroke. ARISTOTLE evaluated ELIQUIS versus warfarin in 18,201 patients with nonvalvular atrial fibrillation who were suitable for warfarin therapy, and AVERROES evaluated ELIQUIS versus aspirin in 5,598 patients with nonvalvular atrial fibrillation who were considered unsuitable for treatment with warfarin.

The Full Prescribing Information for ELIQUIS includes a Boxed Warning for patients who discontinue treatment. Patients on ELIQUIS who discontinue treatment are at an increased risk of thrombotic events. An increased rate of stroke was observed following discontinuation of ELIQUIS in clinical trials in patients with nonvalvular atrial fibrillation. If anticoagulation with ELIQUIS must be discontinued for a reason other than pathological bleeding, coverage with another anticoagulant should be strongly considered.

ELIQUIS increases the risk of bleeding and can cause serious, potentially fatal bleeding. Please see additional Important Safety Information included in this release.

“With a population that is living longer, the prevalence of nonvalvular atrial fibrillation is increasing, but many patients are still not being managed effectively with warfarin,” said Christopher Granger, M.D., Professor of Medicine, Duke Clinical Research Institute, Duke University Medical Center, Durham, N.C., ARISTOTLE lead investigator. “ELIQUIS represents a significant advance over warfarin for health care professionals to reduce the risk of stroke in patients with nonvalvular atrial fibrillation.”

ELIQUIS is an oral Factor Xa inhibitor anticoagulant. By inhibiting Factor Xa, a key blood clotting protein, ELIQUIS decreases thrombin generation and blood clot formation. ELIQUIS does not require routine monitoring using International Normalized Ratio (INR) or other tests of coagulation and there are no known dietary restrictions. ELIQUIS can be taken with or without food.

ELIQUIS is expected to be widely available in the U.S. by the end of January 2013.

Efficacy and Safety Profile of ELIQUIS in Patients with Nonvalvular Atrial Fibrillation

The ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) study was designed to compare the effects of ELIQUIS and warfarin on the risk of stroke and systemic embolism. In ARISTOTLE, 18,201 patients were randomized (9,120 patients to ELIQUIS and 9,081 to warfarin) and were followed for a median of 1.7 years. ARISTOTLE was a double-blind, multi-national trial in patients with nonvalvular atrial fibrillation, and one or more of the following additional risk factors for stroke: prior stroke or transient ischemic attack, prior systemic embolism, age ≥75 years, arterial hypertension requiring treatment, diabetes mellitus, heart failure ≥New York Heart Association Class 2, or left ventricular ejection fraction ≤40%. Patients received treatment with ELIQUIS 5 mg orally twice daily (or 2.5 mg twice daily in patients with at least 2 of the following characteristics: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL) or warfarin (target INR range 2.0-3.0).

ELIQUIS is the only oral anticoagulant to demonstrate superior risk reductions versus warfarin in three key outcomes—stroke and systemic embolism, major bleeding, and all-cause mortality—for patients with nonvalvular atrial fibrillation.

In ARISTOTLE, ELIQUIS was superior to warfarin in the primary efficacy endpoint of stroke or systemic embolism, with a 21% relative risk reduction beyond warfarin (1.27%/year versus 1.60%/year, HR=0.79, p=0.01). Superiority to warfarin was primarily attributable to a reduction in hemorrhagic stroke and ischemic stroke that converted to hemorrhagic stroke. Purely ischemic strokes occurred with similar rates on both drugs.

ELIQUIS was superior to warfarin for the primary safety endpoint of major bleeding, with a 31% relative risk reduction (2.13%/year versus 3.09%/year, HR=0.69, p<0.0001). Major bleeding was defined as clinically overt bleeding that was accompanied by one or more of the following: a decrease in hemoglobin of 2 g/dL or more; a transfusion of 2 or more units of packed red blood cells; bleeding that occurred in at least one of the following critical sites: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal; or bleeding that was fatal.

The incidence of major gastrointestinal (GI) bleeds was lower with ELIQUIS compared to warfarin (0.83%/year versus 0.93%/year, HR=0.89 ). GI bleed includes upper GI, lower GI, and rectal bleeding. ELIQUIS demonstrated a significant reduction in intracranial hemorrhage versus warfarin with a 59% relative risk reduction (0.33%/year versus 0.82%/year, HR=0.41 ). Intracranial hemorrhage included intracerebral (hemorrhagic stroke), subarachnoid, and subdural bleeds. The incidence of major intraocular bleeding was numerically higher with ELIQUIS compared to warfarin (0.21%/year versus 0.14%/year, HR=1.42 ). Intraocular bleed is within the corpus of the eye (a conjunctival bleed is not an intraocular bleed). ELIQUIS demonstrated a significant reduction in fatal bleeds versus warfarin with a 73% relative risk reduction (0.06%/year versus 0.24%/year, HR=0.27 ). Fatal bleed is an adjudicated death because of bleeding during the treatment period and includes both fatal extracranial bleeds and fatal hemorrhagic stroke. Eliquis demonstrated a significant reduction in clinically relevant non major bleeding (CRNM) versus warfarin (2.08%/year for ELIQUIS compared to 3.00%/year for warfarin ). CRNM was defined as clinically overt bleeding that did not satisfy the criteria for major bleeding and that led to hospital admission, physician-guided medical or surgical treatment, or a change in antithrombotic therapy.

ELIQUIS was superior to warfarin in the key secondary endpoint of all-cause mortality, with an 11% relative risk reduction (3.5%/year versus 3.9%/year, HR=0.89, p= 0.046), primarily because of a reduction in cardiovascular death, particularly stroke deaths. Non-vascular death rates were similar in the treatment arms.

The most common and most serious adverse reactions observed in the ARISTOTLE and AVERROES clinical trials with ELIQUIS were related to bleeding. The most common reason for treatment discontinuation was for bleeding-related adverse reactions; in ARISTOTLE, this occurred in 1.7% and 2.5% of patients treated with ELIQUIS and warfarin, respectively. Patients taking ELIQUIS should be carefully observed and counseled on the symptoms and signs of bleeding.

The FDA has determined that a Risk Evaluation and Mitigation Strategy (REMS) is necessary to ensure that the benefits of ELIQUIS outweigh the potential risks in patients with nonvalvular atrial fibrillation. The ELIQUIS REMS consists of a communication plan to inform healthcare professionals about the increased risk of thrombotic events, including stroke when discontinuing ELIQUIS without an adequate alternative anticoagulant and the importance of following the recommendations in the U.S. Prescribing Information on how to convert patients with nonvalvular atrial fibrillation from ELIQUIS to warfarin or other anticoagulants.

ELIQUIS Dosage and Administration

The recommended dose of ELIQUIS for most patients is 5 mg taken orally twice daily. In patients with any two of the following characteristics (age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5mg/dL), the recommended dose of ELIQUIS is 2.5 mg twice daily. The dose of ELIQUIS should be decreased to 2.5 mg twice daily when coadministered with drugs that are strong dual inhibitors of CYP3A4 and P-gp, (e.g., ketoconazole, itraconazole, ritonavir, or clarithromycin). In patients already taking 2.5 mg twice daily, avoid coadministration of ELIQUIS with strong dual inhibitors of CYP3A4 and P-gp. ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding. ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be non-critical in location and easily controlled. For more detailed information on the dosing of ELIQUIS, please refer to Section 2 of the Full Prescribing Information.

IMPORTANT SAFETY INFORMATION for ELIQUIS® (apixaban) 2.5 mg and 5 mg tablets

WARNING: DISCONTINUING ELIQUIS IN PATIENTS WITHOUT ADEQUATE CONTINUOUS ANTICOAGULATION INCREASES RISK OF STROKE.

Discontinuing ELIQUIS places patients at an increased risk of thrombotic events. An increased rate of stroke was observed following discontinuation of ELIQUIS in clinical trials in patients with nonvalvular atrial fibrillation. If anticoagulation with ELIQUIS must be discontinued for a reason other than pathological bleeding, coverage with another anticoagulant should be strongly considered.

CONTRAINDICATIONS

  • Active pathological bleeding
  • Severe hypersensitivity reaction to ELIQUIS (apixaban) (i.e., anaphylactic reactions)

WARNINGS AND PRECAUTIONS

  • Increased Risk of Stroke with Discontinuation of ELIQUIS: Discontinuing ELIQUIS in the absence of adequate alternative anticoagulation increases the risk of thrombotic events. An increased rate of stroke was observed during the transition from ELIQUIS to warfarin in clinical trials in patients with nonvalvular atrial fibrillation. If ELIQUIS must be discontinued for a reason other than pathological bleeding, consider coverage with another anticoagulant.
  • Bleeding Risk: ELIQUIS increases the risk of bleeding and can cause serious, potentially fatal bleeding. Concomitant use of drugs affecting hemostasis increases the risk of bleeding including aspirin and other anti-platelet agents, other anticoagulants, heparin, thrombolytic agents, SSRIs, SNRIs, and NSAIDs. Patients should be made aware of signs or symptoms of blood loss and instructed to immediately report to an emergency room. Discontinue ELIQUIS in patients with active pathological hemorrhage.
  • There is no established way to reverse the anticoagulant effect of apixaban, which can be expected to persist for about 24 hours after the last dose (i.e., about two half-lives). A specific antidote for ELIQUIS is not available. Because of high plasma protein binding, apixaban is not expected to be dialyzable. Protamine sulfate and vitamin K would not be expected to affect the anticoagulant activity of apixaban. There is no experience with antifibrinolytic agents (tranexamic acid, aminocaproic acid) in individuals receiving apixaban. There is neither scientific rationale for reversal nor experience with systemic hemostatics (desmopressin and aprotinin) in individuals receiving apixaban. Use of procoagulant reversal agents such as prothrombin complex concentrate, activated prothrombin complex concentrate, or recombinant factor VIIa may be considered but has not been evaluated in clinical studies. Activated charcoal reduces absorption of apixaban thereby lowering apixaban plasma concentrations.
  • Prosthetic Heart Valves: The safety and efficacy of ELIQUIS has not been studied in patients with prosthetic heart valves and is not recommended in these patients.

ADVERSE REACTIONS

The most common and most serious adverse reactions reported with ELIQUIS (apixaban) were related to bleeding.

DISCONTINUATIONS FOR SURGERY AND OTHER INTERVENTIONS

ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding. ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be noncritical in location and easily controlled.

DRUG INTERACTIONS

  • Strong Dual Inhibitors of CYP3A4 and P-gp: Inhibitors of CYP3A4 and P-gp increase exposure to apixaban and increase the risk of bleeding. Decrease the dose of ELIQUIS to 2.5 mg twice daily when coadministered with drugs that are strong dual inhibitors of CYP3A4 and P-gp, (e.g., ketoconazole, itraconazole, ritonavir, or clarithromycin). In patients already taking ELIQUIS at a dose of 2.5 mg daily, avoid coadministration with strong dual inhibitors of CYP3A4 and P-gp.
  • Strong Dual Inducers of CYP3A4 and P-gp: Inducers of CYP3A4 and P-gp decrease exposure to apixaban and increase the risk of stroke. Avoid concomitant use of ELIQUIS with strong dual inducers of CYP3A4 and P-gp (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort) because such drugs will decrease exposure to apixaban.
  • Anticoagulants and Antiplatelet Agents: Coadministration of antiplatelet agents, fibrinolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding.

PREGNANCY CATEGORY B

There are no adequate and well-controlled studies of ELIQUIS in pregnant women. Treatment is likely to increase the risk of hemorrhage during pregnancy and delivery. ELIQUIS should be used during pregnancy only if the potential benefit outweighs the potential risk to the mother and fetus.

INDICATION

ELIQUIS is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

Please see full Prescribing Information including BOXED WARNING and Medication Guide available at www.bms.com.

About the Bristol-Myers Squibb/Pfizer Collaboration

In 2007, Pfizer and Bristol-Myers Squibb entered into a worldwide collaboration to develop and commercialize ELIQUIS, an investigational oral anticoagulant discovered by Bristol-Myers Squibb. This global alliance combines Bristol-Myers Squibb’s long-standing strengths in cardiovascular drug development and commercialization with Pfizer’s global scale and expertise in this field.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

Pfizer Inc.: Working together for a healthier world™

At Pfizer, we apply science and our global resources to improve health and well-being at every stage of life. We strive to set the standard for quality, safety and value in the discovery, development and manufacturing of medicines for people and animals. Our diversified global health care portfolio includes human and animal biologic and small molecule medicines and vaccines; as well as many of the world’s best-known consumer products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as the world’s leading biopharmaceutical company, we also collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, Pfizer has worked to make a difference for all who rely on us.

Bristol-Myers Squibb Forward-Looking Statement

This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding product development. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that ELIQUIS will become a commercially successful product. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb’s business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2011, in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

PFIZER DISCLOSURE NOTICE:

The information contained in this release is as of January 2, 2013. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.

This release contains forward-looking information about ELIQUIS (apixaban) that involves substantial risks and uncertainties. Such risks and uncertainties include, among other things, (i) the uncertainties regarding the commercial success of ELIQUIS in the U.S. for the reduction of the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation; (ii) the ability to meet the anticipated timing for the availability of Eliquis in the U.S.; (iii) decisions by regulatory authorities in jurisdictions in which applications are pending or may be filed for ELIQUIS for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation regarding whether and when to approve such applications, as well as their decisions regarding labeling and other matters that could affect the availability or commercial potential of that indication in such jurisdictions; and (iv) competitive developments.

A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2011 and in its reports on Form 10-Q and Form 8-K.

This press release has an accompanying Smart Marketing Page providing further details about the organization, products and services introduced above. You can access the Smart Marketing Page via the following link:
http://smp.newshq.businesswire.com/pages/eliquis-apixaban-tablets-now-approved

Photos/Multimedia Gallery Available: http://www.businesswire.com/multimedia/home/20130102005516/en/

Eliquis is the brand name of the prescription medicine apixaban, which is used to prevent strokes and blood clots in people with atrial fibrillation (a condition characterized by an irregular heartbeat).

This medicine is also given to treat or reduce the risk of developing deep vein thrombosis (DVT; a blood clot that usually develops in the leg) and pulmonary embolism (PE; a blood clot in the lung).

In addition, Eliquis may be prescribed after hip or knee replacement surgery to help prevent DVT or PE.

Eliquis belongs to a class of drugs called factor Xa inhibitors, often also called blood thinners. It works by preventing certain enzymes (known as factor Xa) in the blood from forming a blood clot.

The Food and Drug Administration (FDA) approved Eliquis in 2012. It’s marketed by Bristol-Myers Squibb Company.

Eliquis Warnings

Eliquis contains a black box warning because it may cause a higher risk of stroke when people with atrial fibrillation stop taking it.

Don’t suddenly stop using this medicine without first talking to your doctor. Continue to take Eliquis even if you feel well, and don’t miss any doses.

If you need to stop using Eliquis, your healthcare provider may prescribe another blood thinner to help prevent stroke.

Eliquis contains another black box warning because it may cause a serious blood clot around your spinal cord if you have an epidural, spinal anesthesia, or a spinal puncture while taking it.

This blood clot can lead to long-term or permanent paralysis.

Tell your doctor if you currently have, or have a history of having:

  • Epidural catheters
  • Spinal punctures
  • A spinal deformity
  • Spinal surgery

It’s also important to let your healthcare provider know if you’re taking any drugs that may affect how your blood clots, including:

  • Aggrastat (tirofiban)
  • Agrylin (anagrelide)
  • Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), such as Advil or Motrin (ibuprofen), Indocin or Tivorbex (indomethacin), ketoprofen, and Aleve, Anaprox, or Naprosyn (naproxen)
  • Brilinta (ticagrelor)
  • Coumadin or Jantoven (warfarin)
  • Effient (prasugrel)
  • Heparin
  • Integrilin (eptifibatide)
  • Persantine (dipyridamole)
  • Plavix (clopidogrel)
  • Pletal (cilostazol)
  • Ticlopidine

Eliquis may interact with certain medicines that are commonly used during a medical emergency.

It’s important that you or a family member tells healthcare professionals that you’re taking Eliquis, in case of an emergency.

Tell your doctor immediately if you experience any of the following symptoms while using this medicine:

  • Muscle weakness, especially in the legs or feet
  • Numbness or tingling, especially in the legs
  • Back pain
  • Loss of control of your bladder or bowels

Don’t take Eliquis if you have an artificial heart valve or active bleeding.

This drug may cause you to bleed or bruise more easily.

Try to avoid activities that increase your risk of bleeding or injury while using Eliquis. Call your doctor right away if you injure yourself — especially if you hit your head.

Let your healthcare provider know you’re using this medicine before having any type of medical or dental procedure.

Before starting treatment with Eliquis, tell your doctor if you have, or have ever had:

  • Kidney disease
  • Liver disease
  • Bleeding problems
  • A stroke
  • Allergies to medicines

Also, let your doctor know if you’re age 80 or older, or if you weigh 132 pounds or less.

Keep all appointments with your doctor and laboratory while being treated with Eliquis. Your healthcare provider will probably order frequent tests to check your body’s response to this medicine.

Pregnancy and Eliquis

Eliquis isn’t believed to harm an unborn baby if taken during pregnancy.

But it may increase the risk of bleeding during your pregnancy or delivery.

Tell your doctor if you’re pregnant, or might become pregnant, while using Eliquis.

It’s not known whether this drug passes into breast milk. Don’t breastfeed a baby while taking Eliquis.

Bad mix: Blood thinners and NSAIDs

Image: Anita_Bonita/Getty Images

Updated: December 16, 2019Published: October, 2013

Take the lowest dose of NSAIDs and stop using them as soon as possible.

Blood thinners are usually given to people at risk for developing blood clots from conditions, such as abnormal heart rhythms. Use of these lifesaving medications requires caution with other drugs, especially painkillers called nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil) or naproxen (Aleve). But plenty of people take the risk to relieve aches and pains. “Many of the patients who need blood thinners are older and therefore at risk for arthritis, so it’s not infrequent for a patient to be on both a blood thinner and an NSAID,” says cardiologist Dr. Deepak L. Bhatt, a Harvard Medical School professor.

About blood thinners

Blood thinners come in two classes: Antiplatelet drugs such as aspirin stop platelets from forming clots. Anticoagulants such as warfarin (Coumadin) and the newer direct acting oral anticoagulants (DOACs) lengthen the time it takes to form a blood clot. NSAIDs affect the way platelets work and could interfere with normal blood clotting. “That could raise the risk of bleeding, especially in the digestive tract. Taking them together with blood thinners raises the bleeding risk even more,” says Dr. Bhatt.

What you can do

If you’re taking a blood thinner, your options for pain relief are limited. Sometimes physical therapy can help relieve joint pain by strengthening the muscles that support the joints to better absorb stress. But there are times when painkillers are needed, such as when arthritic pain won’t go away. Acetaminophen (Tylenol) can usually be used, but high doses come with the possible risk of liver damage. “When painkillers are needed, it’s best to use the lowest dose that reduces symptoms and to stop taking them if the symptoms subside,” advises Dr. Bhatt. And make sure you talk to your doctor before mixing any type of painkiller with a blood thinner.

Find the hidden NSAIDs

Sometimes NSAIDs and aspirin are obvious ingredients in over-the-counter remedies, but not always. Talk to your doctor before taking any of these drugs in addition to your blood thinner.

Product name

Used for

Contains

Advil, Motrin, Nuprin

aches, pains, headache

ibuprofen

Aleve

aches, pains, headache

naproxen

Excedrin, Bayer, Bufferin, Asper Gum

aches, pains, headache

aspirin

Alka-Seltzer

indigestion

aspirin

Pepto-Bismol, Maalox, Kaopectate

indigestion, diarrhea

bismuth subsalicylate (related to aspirin)

Advil PM

sleep aid, pain reliever

ibuprofen

Alka-Seltzer plus

common cold

aspirin

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Don’t Eat These Foods If You Take Blood Thinners or Statins

If you take medication for heart disease, it’s important to know what foods to eat, and even more important to know what foods not to eat.

Take Coumadin? Eat fewer foods with vitamin K

Cardiologists report that one of the most common interactions occurs between the blood thinner warfarin (Coumadin®) and foods high in vitamin K, which the body uses to clot blood. Foods high in vitamin K act as an antidote to your medicine. These foods include:

  • Asparagus
  • Broccoli
  • Brussels sprouts
  • Cauliflower
  • Green onions
  • Kale
  • Parsley
  • Spinach

You don’t have to avoid these foods, but eating a mostly plant-based diet can cause problems for some people. You should also limit the amount of green tea, alcohol and cranberry juice you drink.

Take a statin? Don’t eat grapefruit

Grapefruit and other citrus fruits can interfere with how your body metabolizes medicine, which can create problems for people taking statins and certain other drugs.

Take a diuretic? Stay away from sodium

Diuretics rid the body of fluid and become less effective if you eat a diet high in salt. Too much sodium causes the body to retain fluid.

If you have any questions about possible drug interactions, talk to your doctor or pharmacist. He or she can make sure the foods you eat don’t interfere with the effectiveness of the medicines you take.

CLINICAL PHARMACOLOGY

Mechanism Of Action

Apixaban is a selective inhibitor of FXa. It does not require antithrombin III for antithrombotic activity. Apixaban inhibits free and clot-bound FXa, and prothrombinase activity. Apixaban has no direct effect on platelet aggregation, but indirectly inhibits platelet aggregation induced by thrombin. By inhibiting FXa, apixaban decreases thrombin generation and thrombus development.

Pharmacodynamics

As a result of FXa inhibition, apixaban prolongs clotting tests such as prothrombin time (PT), INR, and activated partial thromboplastin time (aPTT). Changes observed in these clotting tests at the expected therapeutic dose, however, are small, subject to a high degree of variability, and not useful in monitoring the anticoagulation effect of apixaban.

The Rotachrom® Heparin chromogenic assay was used to measure the effect of apixaban on FXa activity in humans during the apixaban development program. A concentration-dependent increase in anti-FXa activity was observed in the dose range tested and was similar in healthy subjects and patients with AF.

This test is not recommended for assessing the anticoagulant effect of apixaban.

Effect Of PCCs On Pharmacodynamics Of Eliquis

There is no clinical experience to reverse bleeding with the use of 4-factor PCC products in individuals who have received ELIQUIS.

Effects of 4-factor PCCs on the pharmacodynamics of apixaban were studied in healthy subjects. Following administration of apixaban dosed to steady state, endogenous thrombin potential (ETP) returned to pre-apixaban levels 4 hours after the initiation of a 30-minute PCC infusion, compared to 45 hours with placebo. Mean ETP levels continued to increase and exceeded pre-apixaban levels reaching a maximum (34%-51% increase over pre-apixaban levels) at 21 hours after initiating PCC and remained elevated (21%-27% increase) at the end of the study (69 hours after initiation of PCC). The clinical relevance of this increase in ETP is unknown.

Pharmacodynamic Drug Interaction Studies

Pharmacodynamic drug interaction studies with aspirin, clopidogrel, aspirin and clopidogrel, prasugrel, enoxaparin, and naproxen were conducted. No pharmacodynamic interactions were observed with aspirin, clopidogrel, or prasugrel . A 50% to 60% increase in anti-FXa activity was observed when apixaban was coadministered with enoxaparin or naproxen.

Specific Populations

Renal Impairment: Anti-FXa activity adjusted for exposure to apixaban was similar across renal function categories.

Hepatic Impairment: Changes in anti-FXa activity were similar in patients with mild-to-moderate hepatic impairment and healthy subjects. However, in patients with moderate hepatic impairment, there is no clear understanding of the impact of this degree of hepatic function impairment on the coagulation cascade and its relationship to efficacy and bleeding. Patients with severe hepatic impairment were not studied.

Cardiac Electrophysiology

Apixaban has no effect on the QTc interval in humans at doses up to 50 mg.

Pharmacokinetics

Apixaban demonstrates linear pharmacokinetics with dose-proportional increases in exposure for oral doses up to 10 mg.

Absorption

The absolute bioavailability of apixaban is approximately 50% for doses up to 10 mg of ELIQUIS. Food does not affect the bioavailability of apixaban. Maximum concentrations (Cmax) of apixaban appear 3 to 4 hours after oral administration of ELIQUIS. At doses ≥25 mg, apixaban displays dissolution-limited absorption with decreased bioavailability. Following oral administration of 10 mg of apixaban as 2 crushed 5 mg tablets suspended in 30 mL of water, exposure was similar to that after oral administration of 2 intact 5 mg tablets. Following oral administration of 10 mg of apixaban as 2 crushed 5 mg tablets mixed with 30 g of applesauce, the Cmax and AUC were 20% and 16% lower, respectively, when compared to administration of 2 intact 5 mg tablets. Following administration of a crushed 5 mg ELIQUIS tablet that was suspended in 60 mL D5W and delivered through a nasogastric tube, exposure was similar to that seen in other clinical trials involving healthy volunteers receiving a single oral 5 mg tablet dose.

Distribution

Plasma protein binding in humans is approximately 87%. The volume of distribution (Vss) is approximately 21 liters.

Metabolism

Approximately 25% of an orally administered apixaban dose is recovered in urine and feces as metabolites. Apixaban is metabolized mainly via CYP3A4 with minor contributions from CYP1A2, 2C8, 2C9, 2C19, and 2J2. O-demethylation and hydroxylation at the 3-oxopiperidinyl moiety are the major sites of biotransformation.

Unchanged apixaban is the major drug-related component in human plasma; there are no active circulating metabolites.

Elimination

Apixaban is eliminated in both urine and feces. Renal excretion accounts for about 27% of total clearance. Biliary and direct intestinal excretion contributes to elimination of apixaban in the feces.

Apixaban has a total clearance of approximately 3.3 L/hour and an apparent half-life of approximately 12 hours following oral administration.

Apixaban is a substrate of transport proteins: P-gp and breast cancer resistance protein.

Drug Interaction Studies

In in vitro apixaban studies at concentrations significantly greater than therapeutic exposures, no inhibitory effect on the activity of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2D6, CYP3A4/5, or CYP2C19, nor induction effect on the activity of CYP1A2, CYP2B6, or CYP3A4/5 were observed. Therefore, apixaban is not expected to alter the metabolic clearance of coadministered drugs that are metabolized by these enzymes. Apixaban is not a significant inhibitor of P-gp.

The effects of coadministered drugs on the pharmacokinetics of apixaban are summarized in Figure 2 .

Figure 2: Effect of Coadministered Drugs on the Pharmacokinetics of Apixaban

In dedicated studies conducted in healthy subjects, famotidine, atenolol, prasugrel, and enoxaparin did not meaningfully alter the pharmacokinetics of apixaban.

In studies conducted in healthy subjects, apixaban did not meaningfully alter the pharmacokinetics of digoxin, naproxen, atenolol, prasugrel, or acetylsalicylic acid.

The effects of level of renal impairment, age, body weight, and level of hepatic impairment on the pharmacokinetics of apixaban are summarized in Figure 3.

Figure 3: Effect of Specific Populations on the Pharmacokinetics of Apixaban

* ESRD subjects treated with intermittent hemodialysis; reported PK findings are following single dose of apixaban post hemodialysis.
†Results reflect CrCl of 15 mL/min based on regression analysis.
‡ Dashed vertical lines illustrate pharmacokinetic changes that were used to inform dosing recommendations.
§ No dose adjustment is recommended for nonvalvular atrial fibrillation patients unless at least 2 of the following patient characteristics (age greater than or equal to 80 years, body weight less than or equal to 60 kg, or serum creatinine greater than or equal to 1.5 mg/dL) are present.

Gender

A study in healthy subjects comparing the pharmacokinetics in males and females showed no meaningful difference.

Race

The results across pharmacokinetic studies in normal subjects showed no differences in apixaban pharmacokinetics among White/Caucasian, Asian, and Black/African American subjects. No dose adjustment is required based on race/ethnicity.

Hemodialysis In ESRD Subjects

Systemic exposure to apixaban administered as a single 5 mg dose in ESRD subjects dosed immediately after the completion of a 4-hour hemodialysis session (post-dialysis) is 36% higher when compared to subjects with normal renal function (Figure 3).

The systemic exposure to apixaban administered 2 hours prior to a 4-hour hemodialysis session with a dialysate flow rate of 500 mL/min and a blood flow rate in the range of 350 to 500 mL/min is 17% higher compared to those with normal renal function. The dialysis clearance of apixaban is approximately 18 mL/min. The systemic exposure of apixaban is 14% lower on dialysis when compared to not on dialysis.

Protein binding was similar (92%-94%) between healthy controls and ESRD subjects during the on-dialysis and off-dialysis periods.

Clinical Studies

Reduction Of Risk Of Stroke And Systemic Embolism In Nonvalvular Atrial Fibrillation

ARISTOTLE

Evidence for the efficacy and safety of ELIQUIS was derived from ARISTOTLE, a multinational, double-blind study in patients with nonvalvular AF comparing the effects of ELIQUIS and warfarin on the risk of stroke and non-central nervous system (CNS) systemic embolism. In ARISTOTLE, patients were randomized to ELIQUIS 5 mg orally twice daily (or 2.5 mg twice daily in subjects with at least 2 of the following characteristics: age greater than or equal to 80 years, body weight less than or equal to 60 kg, or serum creatinine greater than or equal to 1.5 mg/dL) or to warfarin (targeted to an INR range of 2.0-3.0). Patients had to have one or more of the following additional risk factors for stroke:

  • prior stroke or transient ischemic attack (TIA)
  • prior systemic embolism
  • age greater than or equal to 75 years
  • arterial hypertension requiring treatment
  • diabetes mellitus
  • heart failure ≥New York Heart Association Class 2
  • left ventricular ejection fraction ≤40%

The primary objective of ARISTOTLE was to determine whether ELIQUIS 5 mg twice daily (or 2.5 mg twice daily) was effective (noninferior to warfarin) in reducing the risk of stroke (ischemic or hemorrhagic) and systemic embolism. Superiority of ELIQUIS to warfarin was also examined for the primary endpoint (rate of stroke and systemic embolism), major bleeding, and death from any cause.

A total of 18,201 patients were randomized and followed on study treatment for a median of 89 weeks. Forty-three percent of patients were vitamin K antagonist (VKA) “naive,” defined as having received ≤30 consecutive days of treatment with warfarin or another VKA before entering the study. The mean age was 69 years and the mean CHADS2 score (a scale from 0 to 6 used to estimate risk of stroke, with higher scores predicting greater risk) was 2.1. The population was 65% male, 83% Caucasian, 14% Asian, and 1% Black. There was a history of stroke, TIA, or non-CNS systemic embolism in 19% of patients. Concomitant diseases of patients in this study included hypertension 88%, diabetes 25%, congestive heart failure (or left ventricular ejection fraction ≤40%) 35%, and prior myocardial infarction 14%. Patients treated with warfarin in ARISTOTLE had a mean percentage of time in therapeutic range (INR 2.0-3.0) of 62%.

ELIQUIS was superior to warfarin for the primary endpoint of reducing the risk of stroke and systemic embolism (Table 9 and Figure 4). Superiority to warfarin was primarily attributable to a reduction in hemorrhagic stroke and ischemic strokes with hemorrhagic conversion compared to warfarin. Purely ischemic strokes occurred with similar rates on both drugs.

ELIQUIS also showed significantly fewer major bleeds than warfarin .

Table 9: Key Efficacy Outcomes in Patients with Nonvalvular Atrial Fibrillation in ARISTOTLE (Intent-to-Treat Analysis)

Figure 4: Kaplan-Meier Estimate of Time to First Stroke or Systemic Embolism in ARISTOTLE (Intent-to-Treat Population)

All-cause death was assessed using a sequential testing strategy that allowed testing for superiority if effects on earlier endpoints (stroke plus systemic embolus and major bleeding) were demonstrated. ELIQUIS treatment resulted in a significantly lower rate of all-cause death (p = 0.046) than did treatment with warfarin, primarily because of a reduction in cardiovascular death, particularly stroke deaths. Non vascular death rates were similar in the treatment arms.

In ARISTOTLE, the results for the primary efficacy endpoint were generally consistent across most major subgroups including weight, CHADS2 score (a scale from 0 to 6 used to predict risk of stroke in patients with AF, with higher scores predicting greater risk), prior warfarin use, level of renal impairment, geographic region, and aspirin use at randomization (Figure 5).

Figure 5: Stroke and Systemic Embolism Hazard Ratios by Baseline Characteristics – ARISTOTLE Study

Note: The figure above presents effects in various subgroups, all of which are baseline characteristics and all of which were prespecified, if not the groupings. The 95% confidence limits that are shown do not take into account how many comparisons were made, nor do they reflect the effect of a particular factor after adjustment for all other factors. Apparent homogeneity or heterogeneity among groups should not be over-interpreted.

At the end of the ARISTOTLE study, warfarin patients who completed the study were generally maintained on a VKA with no interruption of anticoagulation. ELIQUIS patients who completed the study were generally switched to a VKA with a 2-day period of coadministration of ELIQUIS and VKA, so that some patients may not have been adequately anticoagulated after stopping ELIQUIS until attaining a stable and therapeutic INR. During the 30 days following the end of the study, there were 21 stroke or systemic embolism events in the 6791 patients (0.3%) in the ELIQUIS arm compared to 5 in the 6569 patients (0.1%) in the warfarin arm .

AVERROES

In AVERROES, patients with nonvalvular atrial fibrillation thought not to be candidates for warfarin therapy were randomized to treatment with ELIQUIS 5 mg orally twice daily (or 2.5 mg twice daily in selected patients) or aspirin 81 to 324 mg once daily. The primary objective of the study was to determine if ELIQUIS was superior to aspirin for preventing the composite outcome of stroke or systemic embolism. AVERROES was stopped early on the basis of a prespecified interim analysis showing a significant reduction in stroke and systemic embolism for ELIQUIS compared to aspirin that was associated with a modest increase in major bleeding (Table 10) .

Table 10: Key Efficacy Outcomes in Patients with Nonvalvular Atrial Fibrillation in AVERROES

Prophylaxis Of Deep Vein Thrombosis Following Hip Or Knee Replacement Surgery

The clinical evidence for the effectiveness of ELIQUIS is derived from the ADVANCE-1, ADVANCE-2, and ADVANCE-3 clinical trials in adult patients undergoing elective hip (ADVANCE-3) or knee (ADVANCE-2 and ADVANCE-1) replacement surgery. A total of 11,659 patients were randomized in 3 double-blind, multi-national studies. Included in this total were 1866 patients age 75 or older, 1161 patients with low body weight (≤60 kg), 2528 patients with Body Mass Index ≥33 kg/m2, and 625 patients with severe or moderate renal impairment.

In the ADVANCE-3 study, 5407 patients undergoing elective hip replacement surgery were randomized to receive either ELIQUIS 2.5 mg orally twice daily or enoxaparin 40 mg subcutaneously once daily. The first dose of ELIQUIS was given 12 to 24 hours post surgery, whereas enoxaparin was started 9 to 15 hours prior to surgery. Treatment duration was 32 to 38 days.

In patients undergoing elective knee replacement surgery, ELIQUIS 2.5 mg orally twice daily was compared to enoxaparin 40 mg subcutaneously once daily (ADVANCE-2, N=3057) or enoxaparin 30 mg subcutaneously every 12 hours (ADVANCE-1, N=3195). In the ADVANCE-2 study, the first dose of ELIQUIS was given 12 to 24 hours post surgery, whereas enoxaparin was started 9 to 15 hours prior to surgery. In the ADVANCE-1 study, both ELIQUIS and enoxaparin were initiated 12 to 24 hours post surgery. Treatment duration in both ADVANCE-2 and ADVANCE-1 was 10 to 14 days.

In all 3 studies, the primary endpoint was a composite of adjudicated asymptomatic and symptomatic DVT, nonfatal PE, and all-cause death at the end of the double-blind intended treatment period. In ADVANCE-3 and ADVANCE-2, the primary endpoint was tested for noninferiority, then superiority, of ELIQUIS to enoxaparin. In ADVANCE-1, the primary endpoint was tested for noninferiority of ELIQUIS to enoxaparin.

The efficacy data are provided in Tables 11 and 12.

Table 11: Summary of Key Efficacy Analysis Results During the Intended Treatment Period for Patients Undergoing Elective Hip Replacement Surgery*

Table 12: Summary of Key Efficacy Analysis Results During the Intended Treatment Period for Patients Undergoing Elective Knee Replacement Surgery*

The efficacy profile of ELIQUIS was generally consistent across subgroups of interest for this indication (e.g., age, gender, race, body weight, renal impairment).

Treatment Of DVT And PE And Reduction In The Risk Of Recurrence Of DVT And PE

Efficacy and safety of ELIQUIS for the treatment of DVT and PE, and for the reduction in the risk of recurrent DVT and PE following 6 to 12 months of anticoagulant treatment was derived from the AMPLIFY and AMPLIFY-EXT studies. Both studies were randomized, parallel-group, double-blind trials in patients with symptomatic proximal DVT and/or symptomatic PE. All key safety and efficacy endpoints were adjudicated in a blinded manner by an independent committee.

AMPLIFY

The primary objective of AMPLIFY was to determine whether ELIQUIS was noninferior to enoxaparin/warfarin for the incidence of recurrent VTE (venous thromboembolism) or VTE-related death. Patients with an objectively confirmed symptomatic DVT and/or PE were randomized to treatment with ELIQUIS 10 mg twice daily orally for 7 days followed by ELIQUIS 5 mg twice daily orally for 6 months, or enoxaparin 1 mg/kg twice daily subcutaneously for at least 5 days (until INR ≥2) followed by warfarin (target INR range 2.0-3.0) orally for 6 months. Patients who required thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent, and patients with creatinine clearance <25 mL/min, significant liver disease, an existing heart valve or atrial fibrillation, or active bleeding were excluded from the AMPLIFY study. Patients were allowed to enter the study with or without prior parenteral anticoagulation (up to 48 hours).

A total of 5244 patients were evaluable for efficacy and were followed for a mean of 154 days in the ELIQUIS group and 152 days in the enoxaparin/warfarin group. The mean age was 57 years. The AMPLIFY study population was 59% male, 83% Caucasian, 8% Asian, and 4% Black. For patients randomized to warfarin, the mean percentage of time in therapeutic range (INR 2.0-3.0) was 60.9%.

Approximately 90% of patients enrolled in AMPLIFY had an unprovoked DVT or PE at baseline. The remaining 10% of patients with a provoked DVT or PE were required to have an additional ongoing risk factor in order to be randomized, which included previous episode of DVT or PE, immobilization, history of cancer, active cancer, and known prothrombotic genotype.

ELIQUIS was shown to be noninferior to enoxaparin/warfarin in the AMPLIFY study for the primary endpoint of recurrent symptomatic VTE (nonfatal DVT or nonfatal PE) or VTE-related death over 6 months of therapy (Table 13).

Table 13: Efficacy Results in the AMPLIFY Study

In the AMPLIFY study, patients were stratified according to their index event of PE (with or without DVT) or DVT (without PE). Efficacy in the initial treatment of VTE was consistent between the two subgroups.

AMPLIFY-EXT

Patients who had been treated for DVT and/or PE for 6 to 12 months with anticoagulant therapy without having a recurrent event were randomized to treatment with ELIQUIS 2.5 mg orally twice daily, ELIQUIS 5 mg orally twice daily, or placebo for 12 months. Approximately one-third of patients participated in the AMPLIFY study prior to enrollment in the AMPLIFY-EXT study.

A total of 2482 patients were randomized to study treatment and were followed for a mean of approximately 330 days in the ELIQUIS group and 312 days in the placebo group. The mean age in the AMPLIFY-EXT study was 57 years. The study population was 57% male, 85% Caucasian, 5% Asian, and 3% Black.

The AMPLIFY-EXT study enrolled patients with either an unprovoked DVT or PE at baseline (approximately 92%) or patients with a provoked baseline event and one additional risk factor for recurrence (approximately 8%). However, patients who had experienced multiple episodes of unprovoked DVT or PE were excluded from the AMPLIFY-EXT study. In the AMPLIFY-EXT study, both doses of ELIQUIS were superior to placebo in the primary endpoint of symptomatic, recurrent VTE (nonfatal DVT or nonfatal PE), or all-cause death (Table 14).

Table 14: Efficacy Results in the AMPLIFY-EXT Study

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