Eliquis

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from light, excess heat and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Keep all appointments with your doctor.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

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.

Eliquis

ELIQUIS (apixaban), a factor Xa (FXa) inhibitor, is chemically described as 1-(4-methoxyphenyl)-7- oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide. Its molecular formula is C25H25N5O4, which corresponds to a molecular weight of 459.5. Apixaban has the following structural formula:

Apixaban is a white to pale-yellow powder. At physiological pH (1.2-6.8), apixaban does not ionize; its aqueous solubility across the physiological pH range is ~0.04 mg/mL.

ELIQUIS tablets are available for oral administration in strengths of 2.5 mg and 5 mg of apixaban with the following inactive ingredients: anhydrous lactose, microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulfate, and magnesium stearate. The film coating contains lactose monohydrate, hypromellose, titanium dioxide, triacetin, and yellow iron oxide (2.5 mg tablets) or red iron oxide (5 mg tablets).

• Bristol-Myers Squibb Co.

Eliquis is part of the drug class:

• Direct factor Xa inhibitors

You may have a higher risk of bleeding if you take Eliquis and take other medicines that increase your risk of bleeding, including:

• aspirin or aspirin-containing products
• long-term (chronic) use of nonsteroidal anti-inflammatory drugs (NSAIDs)
• warfarin sodium (Coumadin, Jantoven)
• any medicine that contains heparin
• selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs)
• other medicines to help prevent or treat blood clots

Tell your doctor if you take any of these medicines. Ask your doctor or pharmacist if you are not sure if your medicine is one listed above.

WARNING: DISCONTINUING THIS MEDICATION 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.

• Binds selectively and with high affinity to active site of factor Xa; inhibits free and clot-bound factor Xa and prothrombinase activity.1 38 42

• Inhibition of coagulation factor Xa prevents conversion of prothrombin to thrombin and subsequent thrombus formation.1 28 42

• Unlike fondaparinux, heparin, and LMWHs, apixaban blocks factor Xa directly and does not require a cofactor (antithrombin III) to exert its anticoagulant activity.1 38 42

• Inhibits factor Xa activity and prolongs PT, aPTT, and HepTest (an indirect measure of factor Xa activity) in a concentration-dependent manner.1 8 28

Eliquis is contraindicated in patients with the following conditions:

Pregnancy

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.

Treatment of pregnant rats, rabbits, and mice after implantation until the end of gestation resulted in fetal exposure to apixaban, but was not associated with increased risk for fetal malformations or toxicity. No maternal or fetal deaths were attributed to bleeding. Increased incidence of maternal bleeding was observed in mice, rats, and rabbits at maternal exposures that were 19, 4, and 1 times, respectively, the human exposure of unbound drug, based on area under plasma-concentration time curve (AUC) comparisons at the maximum recommended human dose (MRHD) of 10 mg (5 mg twice daily).

Labor and Delivery

Safety and effectiveness of Eliquis during labor and delivery have not been studied in clinical trials. Consider the risks of bleeding and of stroke in using Eliquis in this setting [see Warnings and Precautions (5.2)].

Treatment of pregnant rats from implantation (gestation Day 7) to weaning (lactation Day 21) with apixaban at a dose of 1000 mg/kg (about 5 times the human exposure based on unbound apixaban) did not result in death of offspring or death of mother rats during labor in association with uterine bleeding. However, increased incidence of maternal bleeding, primarily during gestation, occurred at apixaban doses of ≥25 mg/kg, a dose corresponding to ≥1.3 times the human exposure.

Nursing Mothers

It is unknown whether apixaban or its metabolites are excreted in human milk. Rats excrete apixaban in milk (12% of the maternal dose).

Women should be instructed either to discontinue breastfeeding or to discontinue Eliquis therapy, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Of the total subjects in the ARISTOTLE and AVERROES clinical studies, >69% were 65 and older, and >31% were 75 and older. In the ADVANCE-1, ADVANCE-2, and ADVANCE-3 clinical studies, 50% of subjects were 65 and older, while 16% were 75 and older. In the AMPLIFY and AMPLIFY-EXT clinical studies, >32% of subjects were 65 and older and >13% were 75 and older. No clinically significant differences in safety or effectiveness were observed when comparing subjects in different age groups.

Renal Impairment

The recommended dose is 2.5 mg twice daily in patients with at least two of the following characteristics [see Dosage and Administration (2.1)]:

Patients with End-Stage Renal Disease on Dialysis

Clinical efficacy and safety studies with Eliquis did not enroll patients with end-stage renal disease (ESRD) on dialysis. In patients with ESRD maintained on intermittent hemodialysis, administration of Eliquis at the usually recommended dose [see Dosage and Administration (2.1)] will result in concentrations of apixaban and pharmacodynamic activity similar to those observed in the ARISTOTLE study [see Clinical Pharmacology (12.3)]. It is not known whether these concentrations will lead to similar stroke reduction and bleeding risk in patients with ESRD on dialysis as was seen in ARISTOTLE.

No dose adjustment is recommended for patients with renal impairment, including those with ESRD on dialysis [see Dosage and Administration (2.1)].

Clinical efficacy and safety studies with Eliquis did not enroll patients with ESRD on dialysis or patients with a CrCl <15 mL/min; therefore, dosing recommendations are based on pharmacokinetic and pharmacodynamic (anti-FXa activity) data in subjects with ESRD maintained on dialysis [see Clinical Pharmacology 12.3)].

Hepatic Impairment

No dose adjustment is required in patients with mild hepatic impairment (Child-Pugh class A).

Because patients with moderate hepatic impairment (Child-Pugh class B) may have intrinsic coagulation abnormalities and there is limited clinical experience with Eliquis in these patients, dosing recommendations cannot be provided [see Clinical Pharmacology (12.2)].

Eliquis is not recommended in patients with severe hepatic impairment (Child-Pugh class C) [see Clinical Pharmacology (12.2)].

Applies to apixaban: oral tablet

Along with its needed effects, apixaban (the active ingredient contained in Eliquis) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking apixaban:

• Blood in the eyes
• blood in the urine
• bloody or black, tarry stools
• bruising or purple areas on the skin
• confusion
• constipation
• coughing up blood
• decreased alertness
• difficulty swallowing
• dizziness
• fainting
• fast heartbeat
• headache
• hives, itching, skin rash
• joint pain or swelling
• nausea and vomiting
• nosebleeds
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• redness of the eye
• severe stomach pain
• shortness of breath
• tightness in the chest
• unusual tiredness or weakness
• vomiting of blood or material that looks like coffee grounds

Applies to apixaban: oral tablet

General

The most common adverse events were related to bleeding. Common adverse reactions were anemia, hemorrhage, and nausea.[Ref]

Hematologic

Very common (10% or more): Minor bleed (11.7%)
Common (1% to 10%): Anemia postoperative, clinically relevant nonmajor bleed, hemoglobin decreased, anemia, hemorrhage
Uncommon (0.1% to 1%): Postprocedural hemorrhage, hemoglobin decrease of 2 g/dL or more, transfusion of 2 units or more red blood cells, fatal bleed, thrombocytopenia, hemorrhagic anemia
Rare (less than 0.1%): Bleed at critical site[Ref]

Patients with diabetes had more bleeding events than non-diabetic subjects. Hemorrhage includes hematoma, and vaginal and urethral hemorrhage. Postprocedural hemorrhage includes postprocedural hematoma, wound hemorrhage, vessel puncture site hematoma, and catheter site hemorrhage.[Ref]

Gastrointestinal

Very common (10% or more): Nausea (14.1%)
Common (1% to 10%): Constipation, vomiting, diarrhea, abdominal pain upper, abdominal pain, dyspepsia, gastritis, gastroenteritis, toothache, gingival bleeding, rectal hemorrhage, dyspepsia, gastrointestinal hemorrhage (including hematemesis and melena),
Uncommon (0.1% to 1%): Major gastrointestinal bleed, hematochezia, hemorrhoidal hemorrhage, hematemesis, melena, anal hemorrhage, occult blood positive, occult blood, intra-abdominal hemorrhage, mouth hemorrhage
Rare (less than 0.1%): Retroperitoneal hemorrhage[Ref]

Cardiovascular

Common (1% to 10%): Hypotension, peripheral edema, atrial fibrillation, cardiac failure, hypertension, deep vein thrombosis, tachycardia, cardiac failure congestive, palpitations, thrombosis, angina pectoris, bradycardia, blood pressure increased, procedural hypotension, unstable angina, tachycardia[Ref]

Nervous system

Common (1% to 10%): Dizziness, headache, fatigue, syncope, ischemic stroke, vertigo
Uncommon (0.1% to 1%): Somnolence, cerebrovascular accident, transient ischemic attack, major intracranial bleed, brain hemorrhage, other intracranial or intraspinal hemorrhage (including subdural hematoma, subarachnoid hemorrhage, and spinal hematoma)
Frequency not reported: Stroke[Ref]

Local

Common (1% to 10%): Hematoma, wound hemorrhage, wound secretion
Uncommon (0.1% to 1%): Incision-site hemorrhage, operative hemorrhage, traumatic hematoma, injection site hematoma, vessel puncture site hematoma, application site bleeding, traumatic hemorrhage[Ref]

Ocular

Common (1% to 10%): Cataract, conjunctival hemorrhage, eye hemorrhage
Uncommon (0.1% to 1%): Major intraocular bleed, periorbital hematoma, conjunctival hemorrhage, retinal hemorrhage
Frequency not reported: Ocular hemorrhage[Ref]

Respiratory

Common (1% to 10%): Nasopharyngitis, dyspnea, epistaxis, bronchitis, cough, upper respiratory tract infection, influenza, pneumonia, sinusitis, chronic obstructive pulmonary disease, lower respiratory tract infection, hemoptysis, dyspnea exertional, respiratory tract infection
Uncommon (0.1% to 1%): Dyspnea
Rare (less than 0.1%): Pulmonary embolism, respiratory tract hemorrhage (including pulmonary alveolar hemorrhage, laryngeal hemorrhage, and pharyngeal hemorrhage)[Ref]

Other

Very common (10% or more): Procedural pain (10.3%)
Common (1% to 10%): Pyrexia, chest pain, fall, asthenia, blood creatine phosphokinase increased, pain, body temperature increased, laceration, chest discomfort, tooth extraction
Uncommon (0.1% to 1%): Herpes zoster[Ref]

Genitourinary

Common (1% to 10%): Urinary tract infection, menorrhagia
Uncommon (0.1% to 1%): vaginal hemorrhage, metrorrhagia, menometrorrhagia, genital hemorrhage, blood urine present, red blood cells urine positive, abnormal vaginal hemorrhage, urogenital hemorrhage[Ref]

Renal

Common (1% to 10%): Hematuria, blood creatinine increased, renal failure[Ref]

Musculoskeletal

Common (1% to 10%): Arthralgia, back pain, pain in extremity, osteoarthritis, muscle spasms, musculoskeletal pain, myalgia, arthritis
Uncommon (0.1% to 1%): Muscle hemorrhage, joint swelling[Ref]

Metabolic

Common (1% to 10%): Gout, diabetes mellitus, blood glucose increased, hyperglycemia, hypokalemia, decreased appetite[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Hypersensitivity (including drug hypersensitivity such as skin rash and anaphylactic reaction such as allergic edema)[Ref]

Hepatic

Uncommon (0.1% to 1%): Transaminases increased, AST increased, ALT increased, gamma-glutamyl transferase increased, liver function test abnormal, blood alkaline phosphatase increased, blood bilirubin increased[Ref]

Psychiatric

Common (1% to 10%): Insomnia, depression
Uncommon (0.1% to 1%): Anxiety[Ref]

Dermatologic

Common (1% to 10%): Pruritus, contusion, rash, cellulitis, ecchymosis, erythema, blister
Uncommon (0.1% to 1%): Skin hemorrhage, petechiae, skin rash[Ref]

Oncologic

Uncommon (0.1% to 1%): Basal cell carcinoma[Ref]

Some side effects of Eliquis may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Eliquis reduces the clotting ability of the blood and is used in the treatment and prevention of a number of medical conditions associated with blood clots. It does not require monitoring; however, there is currently no antidote if severe bleeding occurs, although supportive measures (such as FFP) may help restore blood volume.

• May be taken with or without food.
• Tablets may be crushed and mixed with water or apple juice/sauce to make swallowing easier. Swallow mixture straight away and do not save for later use.
• Eliquis is usually dosed twice daily. Check with your doctor what dosage is recommended for you.
• Tell all healthcare providers that you are taking Eliquis. Eliquis may need to be temporarily discontinued at least 48 hours prior to surgery that carries a moderate-to-high risk of unacceptable or clinically significant bleeding; 24 hours before surgery with a low risk of bleeding or if bleeding likely to be noncritical. Bridging therapy is not usually required and Eliquis should be re-started once the risk of bleeding post-surgery has returned to normal.
• Eliquis may also increase your risk of bleeding from a minor fall or bump on the head. Contact your doctor if you experience an injury or have bleeding that will not stop.
• Your doctor may require you to undertake extra monitoring when switching to or from Eliquis.
• Do not stop taking Eliquis suddenly. Your doctor will advise you on how to discontinue Eliquis when or if you no longer require it.