Eliquis Side Effects — Liver Damage, Bleeding & Blood Clots

People taking Eliquis may experience side effects such as headaches, dizziness, fatigue, nausea, gastrointestinal discomfort, joint pain, and rash. The National Institutes of Health reported that after the drug was approved in 2012, reports of mild liver injury occurred, stating “liver injury arose within days of starting apixaban.”

Severe allergic reactions to Eliquis, which cause chest pain, swelling of the face or tongue, labored breathing and dizziness, are a medical emergency. Anyone experiencing these symptoms should call their doctor or 911 immediately.

Dangerous, possibly fatal, adverse events have been associated with Eliquis. The blood thinner can cause bleeding within the skull, hemorrhagic stroke, or gastrointestinal bleeding. Patients taking Eliquis also experienced bleeding at surgical sites following hip or knee replacement surgeries.

Unless the antidote — which is not widely available — is administered, effects should be expected to persist for at least 24 hours after the last dose of the medication is administered.

Patients who stop taking the drug prematurely are also at an increased risk of blood clots and other thrombotic events, such as stroke, while patients who undergo certain spinal or epidural procedures can develop hematomas that can result in long-term or permanent disability and death.

Taking Eliquis Safely

Anticoagulants come with risks, but there are steps you can take to prevent injuries related to serious and common side effects.

Although patients taking Eliquis aren’t required to have their bleeding time monitored the way those taking warfarin are, it’s important to take your dose regularly and inform your doctor — and medical professionals you see for other conditions — about all the medications you are taking. Other drugs may interact with Eliquis.

The Agency for Healthcare Research and Quality offers safety tips and a list of signs and symptoms that may require medical attention.

Common side effects of Eliquis include:

• Chest pain or tightness
• Excessively heavy menstrual bleeding
• Red or brown urine
• Swelling of the face or tongue
• Bruising
• Dizziness
• Bleeding from nose or gums
• Difficulty breathing, wheezing

If you notice any of these symptoms, call your doctor.

Injury prevention is crucial for people who take Eliquis or similar blood thinners because even minor injuries can result in internal bleeding. Be careful when using sharp objects, always wear shoes, and avoid sports and activities that can cause trauma to any part of your body.

Additionally, follow your doctor’s orders regarding your diet. Unlike warfarin, Eliquis is not affected by vitamin K, but if you are concerned about what you are eating or if you have stomach discomfort that makes it hard to eat a balanced diet, call your doctor.

Blood Clots with Early Discontinuation

When a patient stops taking Eliquis prematurely, or suddenly, they are at an increased risk of developing blood clots, according to a black box warning contained in drug labeling for the drug.

Typically, a blood clot forms to stop bleeding when a blood vessel is injured. After the bleeding stops and the area of the body where the bleed occurred is healed, the body breaks down and removes the clot naturally.

But when the blood clots too much or abnormally, or when certain conditions prevent the body from dissolving blood clots properly, blood clotting can become excessive and dangerous.

According to the drug’s label, clinical trials showed an increased rate of stroke observed among patients with atrial fibrillation transitioning from Eliquis to warfarin.

Risk of Spinal or Epidural Blood Clots

Patients who receive spinal or epidural anesthesia or undergo spinal puncture while taking Eliquis, are at risk of developing an epidural or spinal hematoma, or blood clot.

Either type of blood clot can result in long-term or permanent paralysis, according to drug labeling containing a black box warning for Eliquis.

Factors that can increase a patient’s risk of developing an epidural or spinal hematoma include:

• Use of indwelling epidural catheters
• Use of Eliquis with other drugs that affect hemostasis (the process that causes bleeding to stop), such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors or other anticoagulant drugs
• History of traumatic or repeated epidural or spinal punctures
• History of spinal deformity or spinal surgery

Optimal timing between taking Eliquis and undergoing a neuraxial procedure is unknown.

Epidural Hematoma

Spinal Hematoma

Spinal hematomas have also occurred spontaneously in patients taking Eliquis who have not undergone spinal procedures or anesthesia.

A 2018 article in Case Reports in Hematology describes a 75-year-old “previously healthy” woman who developed bruising along her arms and partial paralysis of her leg. The problem started 10 days after an emergency-room doctor had switched her from Pradaxa to Eliquis.

Subsequent testing revealed the woman had developed a subdural hemorrhage that had spread through several regions of her spine, resulting in spinal cord compression. The patient required two spinal surgeries to resolve the complication.

Six months after surgery, the patient was “able to walk alone with the aid of a stick.” But the authors of the study warned that serious spinal hematomas are a “devastating complication” of apixaban and rivaroxaban therapy that requires prompt diagnosis and “early surgical evacuation of the hematoma.”

If not treated swiftly and properly, a spinal or epidural hematoma can be deadly. While it is possible to recover fully from the condition, hematomas of this nature can result in permanent damage to the brain and long-term disability.

Please seek the advice of a medical professional before making health care decisions.

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Side effects, dosage, uses, generic, and more

Eliquis can interact with several other medications. It can also interact with certain supplements as well as certain foods.

Different interactions can cause different effects. For instance, some interactions can interfere with how well a drug works. Other interactions can increase side effects or make them more severe.

Eliquis and other medications

Below are medications that can interact with Eliquis. This section doesn’t contain all drugs that may interact with Eliquis.

Before taking Eliquis, talk with your doctor and pharmacist. Tell them about all prescription, over-the-counter, and other drugs you take. Also tell them about any vitamins, herbs, and supplements you use. Sharing this information can help you avoid potential interactions.

If you have questions about drug interactions that may affect you, ask your doctor or pharmacist.

Eliquis and antiplatelets, including aspirin

Taking Eliquis with an antiplatelet drug can raise your risk for bleeding. You shouldn’t take Eliquis with an antiplatelet drug unless your doctor recommends it. Antiplatelets are drugs that help prevent blood clots. Eliquis also helps prevent blood clots, but it works differently than antiplatelets.

Eliquis works by attaching to an activated blood clotting factor, called factor Xa. (Clotting factors are proteins made by your liver.) Eliquis stops this clotting factor from working, which makes your blood less able to form clots. Antiplatelets, on the other hand, interfere with the binding of platelets. (This is the process that actually starts the formation of blood clots.)

Examples of antiplatelet drugs include:

If you’re taking an antiplatelet drug, ask your doctor if you should continue taking it when you start Eliquis. If your doctor recommends taking Eliquis with an antiplatelet, see them right away if you have any bleeding problems. To learn more, see the “Eliquis side effects” section above.

Eliquis and other anticoagulants

Eliquis is an anticoagulant drug (blood thinner) that helps prevent blood clots. Taking Eliquis with other anticoagulants can raise your risk for bleeding.

You shouldn’t take Eliquis with another anticoagulant drug unless you’re switching from one drug to the other. Examples of other anticoagulant drugs include:

• rivaroxaban (Xarelto)
• dabigatran (Pradaxa)
• edoxaban (Savaysa)
• fondaparinux (Arixtra)
• dalteparin (Fragmin)
• enoxaparin (Lovenox)
• warfarin (Coumadin, Jantoven)
• heparin

If you’re switching from another anticoagulant drug to Eliquis, talk with your doctor about how to do so safely.

Eliquis and ibuprofen or other nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, are medications used to reduce swelling and pain. Ibuprofen also reduces fever. If taken with Eliquis, these drugs raise your risk for bleeding. You shouldn’t take ibuprofen or other NSAIDs while you’re taking Eliquis unless your doctor recommends it.

Examples of NSAIDs that shouldn’t be taken with Eliquis include:

• ibuprofen (Ibu-Tab, Advil, Motrin)
• diclofenac (Voltaren, Zipsor, Zorvolex, Arthrotec)
• naproxen (Naprosyn, Anaprox DS, Naprelan, Aleve)
• meloxicam (Mobic, Vivlodex)
• celecoxib (Celebrex)

Certain over-the-counter cold and flu medications contain ibuprofen or naproxen. Ask your doctor or pharmacist about which cold and flu medications are safe for you to use while you’re taking Eliquis.

If you need to take a pain reliever or any other new medications during your Eliquis treatment, talk with your doctor or pharmacist.

Eliquis and Tylenol (not a known interaction)

Tylenol is a medication that relieves pain and reduces fever. It contains the active drug acetaminophen.

Unlike certain other pain relievers, Eliquis doesn’t interact with Tylenol. If you need a pain reliever or treatment for fever while you’re taking Eliquis, it’s safe to take Tylenol.

Eliquis and certain antidepressants

Taking Eliquis with certain antidepressants can raise your risk for bleeding. Examples of these antidepressants include:

If you need to take one of these antidepressants with Eliquis, talk with your doctor about whether it’s safe for you to use the drug with Eliquis. Your doctor may recommend a different type of antidepressant.

If you do take one of these antidepressants with Eliquis, call your doctor right away if you have any symptoms of serious bleeding. For information about possible symptoms of serious bleeding, see the “Eliquis side effects” section above.

Eliquis and certain antifungal drugs

Taking certain antifungals with Eliquis can increase the level of Eliquis in your body. Taking one of these drugs with Eliquis can raise your risk for bleeding.

Examples of antifungals that can increase Eliquis levels include:

• itraconazole (Sporanox, Onmel, Tolsura)
• ketoconazole

If you need to take one of these antifungal drugs with Eliquis, your doctor may prescribe a lower dosage of Eliquis. If this isn’t possible, your doctor can talk with you about other treatment options.

Eliquis and certain HIV drugs

Taking certain HIV drugs with Eliquis can increase the level of Eliquis in your body. Taking one of these drugs with Eliquis can raise your risk for bleeding.

Examples of HIV drugs that can increase Eliquis levels include:

• cobicistat (Tybost)
• ritonavir (Norvir)

If you need to take one of these HIV drugs with Eliquis, your doctor may prescribe a lower dosage of Eliquis. If this isn’t possible, your doctor can talk with you about other treatment options.

Eliquis and rifampin

Taking the antibiotic rifampin (Rifadin) with Eliquis can lower the level of Eliquis in your body. This could make Eliquis less effective in treating and preventing blood clots.

Rifampin should usually be avoided while you’re taking Eliquis. If you need to take this antibiotic, talk with your doctor about safe treatment options.

Eliquis and certain seizure medications

Taking Eliquis with certain drugs used to treat seizures can lower the level of Eliquis in your body. This could make Eliquis less effective in treating and preventing blood clots.

Examples of seizure drugs that can make Eliquis less effective include:

• carbamazepine (Carbatrol, Equetro, Tegretol)
• fosphenytoin (Cerebyx)
• phenobarbital
• phenytoin (Dilantin, Phenytek)
• primidone (Mysoline)

These seizure drugs should usually be avoided with Eliquis. If you need to take a medication to treat seizures, talk with your doctor about safe treatment options.

Eliquis and herbs and supplements

Below is information about whether Eliquis interacts with certain herbs and supplements.

Eliquis and St John’s wort

Taking St John’s wort with Eliquis can lower the level of Eliquis in your body. This could make Eliquis less effective.

Because of this, you should avoid using St John’s wort while taking Eliquis.

Eliquis and turmeric

It’s not known if turmeric interacts with Eliquis.

Turmeric contains a compound called curcumin, which is known to have anti-inflammatory effects (it can reduce swelling). You shouldn’t use certain anti-inflammatory medications, such as ibuprofen, while taking Eliquis. (See “Eliquis and ibuprofen or other nonsteroidal anti-inflammatory drugs” above to learn more.)

Some research suggests that turmeric may affect the way that Eliquis is broken down in your body. This may lead to higher levels of Eliquis in your body, which could raise your risk for bleeding. However, it’s not known if turmeric affects the level of Eliquis enough to have a significant effect on your bleeding risk.

If you’re interested in using turmeric or curcumin while taking Eliquis, talk with your doctor first.

Eliquis and melatonin

Melatonin may reduce your body’s blood clotting ability. Because Eliquis also reduces blood clotting, it’s possible that taking Eliquis with melatonin could raise your risk for bleeding.

However, this interaction hasn’t been studied, and it’s not known for sure if it occurs. If you want to take melatonin with Eliquis, talk with your doctor first.

Eliquis and vitamin K (not a known interaction)

The way Eliquis works in your body isn’t affected by taking vitamin K.

A different anticoagulant called warfarin (Coumadin, Jantoven) is affected by vitamin K. Large amounts of vitamin K are found in certain foods, such as green leafy vegetables. People taking warfarin shouldn’t make big changes to their dietary intake of vitamin K. However, this isn’t the case with Eliquis.

If you have questions about your vitamin K intake while using Eliquis, talk with your doctor.

Eliquis and foods

Eliquis can interact with grapefruit. Therefore, you should avoid drinking grapefruit juice or eating grapefruit while taking Eliquis.

Eliquis is broken down by a protein in your liver called CYP3A4. Grapefruit and grapefruit juice block this protein from working as it normally does. If CYP3A4 can’t properly break down the drug, the amount of Eliquis in your body can get too high. This may raise your risk for serious side effects.

If you have questions about consuming grapefruit or grapefruit juice during your Eliquis treatment, talk with your doctor.

Eliquis and coffee (not a known interaction)

Drinking coffee or other drinks that contain caffeine doesn’t affect how Eliquis works in your body. In some cases, caffeine can affect a different anticoagulant called warfarin (Coumadin, Jantoven). However, this doesn’t happen with Eliquis.

There’s no need to avoid coffee or other drinks or food that contain caffeine while you’re taking Eliquis.

Eliquis and green leafy vegetables (not a known interaction)

Eating green leafy vegetables doesn’t affect how Eliquis works in your body. These vegetables contain high levels of vitamin K, which can affect a different anticoagulant called warfarin. (See the section above called “Eliquis and vitamin K” to learn more.) However, there is no reason to avoid eating green leafy vegetables while you’re taking Eliquis.

Eliquis and surgery

Surgery carries a risk of bleeding, and this risk is higher if you’re taking Eliquis. If you have a surgery planned, your doctor will typically recommend stopping Eliquis for a few days beforehand. This reduces your risk of bleeding with the surgery.

If you have a surgery planned, talk with your doctor about when you should stop taking Eliquis. You shouldn’t stop taking Eliquis unless your doctor tells you to.

Also talk with your doctor about when you should start taking Eliquis again after the surgery. You may be prescribed a different medication to prevent blood clots during the time you can’t take Eliquis.

If you need emergency surgery while you’re taking Eliquis, you may be given an antidote to Eliquis to reduce your risk for bleeding. (An antidote is a drug that reverses the effect of another drug or substance.) See the “Reversing Eliquis bleeds” section above for more information about this.

Eliquis 5mg Tablet 10’s Price, Uses, Side Effects, Composition

Eliquis 5mg Tablet 10’s belongs to a class of drugs called ‘anticoagulants’ (blood thinners) primarily used to prevent and treat deep vein thrombosis (blood clots in leg veins) and pulmonary embolism (blood clots in the lung). Additionally, Eliquis 5mg Tablet 10’s is used to prevent blood clots in patients with atrial fibrillation (irregular heartbeat). Deep vein thrombosis is a condition in which blood clots form in deep veins usually in legs. Pulmonary embolism is a condition in which blood clot blocks the arteries in the lungs. Atrial fibrillation is a condition that causes irregular, often fast heartbeat. Blood clots are formed to stop bleeding that occurs due to tissues injury. Though blood clots are useful to stop bleeding, they may be harmful when abnormally formed within blood vessels as they block blood vessels and inhibit blood flow to essential organs such as brain, heart or lungs.

Eliquis 5mg Tablet 10’s contains Apixaban that works by inhibiting the action of blood clotting factor (X a) which is an important element of blood clotting. Thereby, it prevents the conversion of fibrinogen (soluble protein) to fibrin (insoluble protein) and helps in preventing blood clots formation.

Take Eliquis 5mg Tablet 10’s irrespective of food and swallow whole with a glass of water. Do not crush, chew or break it. Your doctor will advise you how often you take your tablets based on your medical condition. Some people may experience nausea, anaemia (lack of blood), unusual bleeding, including swelling and bruising. Most of these side effects of Eliquis 5mg Tablet 10’s do not require medical attention and gradually resolve over time. However, if the side effects persist or worsen, please consult your doctor.

If you are known to be allergic to Eliquis 5mg Tablet 10’s or any other medicines, please tell your doctor. If you are pregnant or a nursing mother, it is advised to consult a doctor before using Eliquis 5mg Tablet 10’s. If you have a stomach ulcer, recent bleeding in the brain, kidney or liver problems, high blood pressure or bleeding problems, inform your doctor before taking Eliquis 5mg Tablet 10’s. Your doctor may suggest a blood test called ‘international normalised ratio’ (INR) to check how quickly your blood’s clotting. This test result will help your doctor to decide exactly when you should start taking Eliquis 5mg Tablet 10’s.

Eliquis (apixaban) Drug / Medicine Information

(elle-e-kuis)

apixaban

Consumer Medicine Information

What is in this leaflet

This leaflet answers some common questions about Eliquis.

It does not contain all the available information. It does not take the place of talking
to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking
Eliquis against the benefits it is expected to have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine.

You may need to read it again.

What Eliquis is used for

What Eliquis does

This medicine is used to:

prevent blood clots in your veins after a hip or knee replacement surgery.

After an operation you are at an increased risk of getting blood clots.

treat blood clots occurring in deep veins (Deep Vein Thrombosis [DVT]) and clots in
your lungs (Pulmonary Embolism [PE]) and also to prevent these from recurring.

prevent stroke and blood clots in a condition called atrial fibrillation, which is
a type of abnormal heart rhythm.

With atrial fibrillation, part of the heart does not beat the way it should. This
can lead to blood clots forming and increase your risk of having a stroke.

How Eliquis works

The active substance in Eliquis is apixaban. It belongs to a group of medicines called
antithrombotic agents.

It works by inhibiting a blood clot forming substance called Factor Xa.

Ask your doctor if you have any questions about why this medicine has been prescribed
for you.

Your doctor may have prescribed it for another reason.

This medicine is not addictive.

This medicine is available only with a doctor’s prescription.

This medicine is not expected to affect your ability to drive a car or operate machinery.

Use in Children

There is not enough information to recommend the use of this medicine in children
and adolescents under the age of 18 years.

Before you take Eliquis

When you must not take it

Do not take Eliquis if you have an allergy to:

any medicine containing apixaban

any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

shortness of breath

wheezing or difficulty breathing

swelling of the face, lips, tongue or other parts of the body

rash, itching or hives on the skin

Do not take Eliquis if you have, or have had, any of the following medical conditions:

any disease or injury to a body organ that is actively bleeding or at high risk of
bleeding e.g. bleeding ulcer in the stomach or bowel, recent bleeding in the brain,
cancer at high risk of bleeding

liver disease which leads to an increased risk of bleeding

severely reduced kidney function. Your doctor will determine your kidney function

a recent operation on the brain, spinal column or eye(s)

recent brain or spine injury

abnormalities of any blood vessels that may lead to an increase in bleeding

any blood vessel abnormalities of your oesophagus or “gullet”

any disease or injury to a body organ that could lead to significant bleeding e.g.
stomach ulcers, bowel ulcers.

Do not take Eliquis if you are taking the following medicines:

medicines for fungal infections e.g. ketoconazole, itraconazole, voriconazole or posaconazole,
unless they are only applied to the skin

anti-viral medicines for HIV/AIDS e.g. ritonavir

other medicines to stop your blood from clotting e.g. heparin, enoxaparin, warfarin,
rivaroxaban or dabigatran.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Do not take this medicine after the expiry date printed on the pack or if the packaging
is torn or shows signs of tampering.

If it has expired or is damaged, return it to your pharmacist for disposal.

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, preservatives
or dyes.

Tell your doctor if you have ever been hospitalised for a heart condition (heart attack
or unstable angina).

Tell your doctor if you have ever received a stent placed in the coronary arteries
of your heart.

Tell your doctor if you are 75 years or older or if you have or have had any of the
following medical conditions which may lead to an increased risk of bleeding:

a heart condition known as bacterial endocarditis

type of stroke called “haemorrhagic stroke”

blood disorders that affect your ability to form clots and stop bleeding

recent or past ulcer of your stomach or bowel

moderate or mild kidney disease

liver disease

have a lung condition called bronchiectasis

have had a history of bleeding in your lungs

high blood pressure that is not controlled with medications.

Your doctor may decide to keep you under closer observation.

Tell your doctor if you have a prosthetic heart valve or severe rheumatic heart disease,
especially mitral stenosis (problem with the mitral valve in your heart).

Tell your doctor if you know that you have a disease called antiphospholipid syndrome
(a disorder of the immune system that causes an increased risk of blood clots).

Your doctor who will decide if the treatment may need to be changed.

If you are having hip or knee replacement surgery and your operation involves a catheter
or injection into your spinal column e.g. for epidural or spinal anaesthesia or pain
reduction:

tell your doctor immediately if you get numbness or weakness of your legs or problems
with your bowel or bladder after the end of anaesthesia, because urgent care is necessary.

Tell your doctor if you are pregnant or plan to become pregnant.

Eliquis is not recommended for use in pregnant women. Your doctor can discuss with
you the risks and benefits involved.

Tell your doctor if you are breast-feeding or intend to breast-feed.

Eliquis is not recommended during breast-feeding. You should not breast-feed and take
Eliquis at the same time. The active ingredient in Eliquis may be present in breast
milk and poses a bleeding risk to the baby. You and your doctor should decide if you
will take Eliquis or breast-feed.

If you have not told your doctor about any of the above, tell him/her before you start
taking Eliquis.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including:

all prescription medicines

all medicines, vitamins, herbal supplements or natural therapies you buy without a
prescription from a pharmacy, supermarket, naturopath or health food shop.

Some medicines may be affected by Eliquis or may affect how it works. You may need
different amounts of your medicines, or you may need to take different medicines.
Your doctor will advise you.

Tell your doctor or pharmacist if you are taking any of the following:

medicines used to treat fungal infections such as ketoconazole (Nizoral^®), itraconazole (Sporanox^®), voriconazole (Vfend^®) and posaconazole (Noxafil^®)

anti-viral medicines for HIV/AIDS e.g. ritonavir (Norvir^®)

rifampin or rifampicin (Rifadin^®)

medicines to treat epilepsy such as phenytoin (Dilantin^®), carbamazepine (Tegretol^®), phenobarbitone

St John’s wort

medicines to treat depression such as sertraline, citalopram and venlafaxine

medicines used to treat pain and inflammation including non-steroidal anti-inflammatory
drugs (NSAIDs) such as naproxen (Naprosyn^®) or aspirin (Aspro^®)

other medicines used to prevent blood clots such as enoxaparin (Clexane^®), clopidogrel (Iscover^®, Plavix^®), ticagrelor (Brilinta), prasugrel (Effient), heparin, fondaparinux (Arixtra^®), bivalirudin (Angiomax^®), rivaroxaban (Xarelto^®), dabigatran (Pradaxa^®), dipyridamole (Persantin®)

quinidine

verapamil

diltiazem

amiodarone

the antibiotic, clarithromycin.

(Not all brand names are given above so check with your doctor or pharmacist).

Your doctor and pharmacist have more information on medicines to be careful with or
avoid while taking this medicine.

How to take Eliquis

Follow all directions given to you by your doctor or pharmacist carefully.

They may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask your doctor or pharmacist
for help.

How much to take

Your doctor will tell you how many tablets you need to take each day.

If you are having hip or knee replacement surgery

The recommended dose is one 2.5 mg tablet taken twice a day.

If you have blood clots

The recommended dose to treat blood clots is two 5 mg tablets taken twice a day for
7 days, then one 5 mg tablet taken twice a day.

The recommended dose to prevent blood clots that recur is one 2.5 mg tablet taken
twice daily.

If you have atrial fibrillation

The recommended dose is normally one 5 mg tablet taken twice a day.

The recommended dose is one 2.5 mg tablet taken twice a day if you meet any two of
the following:

are 80 years or older

weigh 60 kilograms or under

have reduced kidney function.

How to take it

Swallow the tablet(s) whole with a full glass of water.

If you are unable to swallow the tablet(s) whole, follow the steps below to crush
the tablet(s). This will help make sure that all of the crushed tablet(s) will be
taken.

use a mortar and pestle or a similar device to crush the tablet(s)

transfer the powder to a drinking glass or a small bowl

when using water, 5% dextrose in water or apple juice:

add a small amount of water/5% dextrose in water/apple juice (30 mL) to the mortar
and pestle/device and stir

transfer the water/5% dextrose in water/apple juice to the drinking glass

mix the powder with the water/5% dextrose in water/apple juice and drink right away

rinse the glass with a small amount of water/5% dextrose in water/apple juice and
drink right away.

when using apple sauce:

mix the powder with a small amount of apple sauce (30 g) in a small bowl and eat with
a spoon right away

add a small amount of water (30 mL) to the mortar and pestle/device and stir

transfer the water to the bowl and drink right away

rinse the bowl and the spoon with a small amount of water and drink right away.

If necessary, your doctor may also give you the crushed tablet(s) mixed in 60 mL of
water or 5% dextrose in water, through a nasogastric tube.

It does not matter if you take this medicine before or after food.

When to take it

Take the first tablet as directed by your doctor.

If you are having hip or knee replacement surgery it is usual to start taking your
tablets 12 to 24 hours after your operation.

Take your medicine at about the same time each day.

Taking it at the same time each day will have the best effect. It will also help you
remember when to take it.

How long to take it

Continue taking your medicine for as long as your doctor tells you.

Do not stop taking your medicine or lower the dosage without checking with your doctor.

If you stop taking it suddenly, you may be at an increased risk of developing a blood
clot, which can lead to serious problems such as a stroke if you have atrial fibrillation.

If you are having hip or knee replacement surgery

If you have had a hip replacement, you will usually take the tablets for about 5 weeks.

If you have had a knee replacement, you will usually take the tablets for about 2
weeks.

If you have blood clots

To treat blood clots you will usually take the tablets for up to 6 months. If necessary,
you may need to continue taking the tablets, usually at a lower dose, to prevent further
blood clots.

If you have atrial fibrillation

Continue taking your medicine for as long as your doctor tells you.

If you require cardioversion

If your abnormal heartbeat needs to be restored by a procedure called cardioversion,
take your medicine at the times your doctor tells you, to help prevent blood clots
that may result in strokes or other problems.

If you forget to take it

Take your next tablet as soon as you remember, then continue taking the tablets as
normal (twice a day).

Do not take a double dose to make up for the forgotten tablet.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for some
hints.

If you take too much (overdose)

Immediately telephone your doctor, or the Poisons Information Centre on 13 11 26 for
advice, or go to the Accident and Emergency Department at the nearest hospital, if
you think that you or anyone else may have taken too much Eliquis.

Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

Symptoms of an overdose may include bleeding that does not stop.

While you are taking Eliquis

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist
that you are taking Eliquis.

Tell any other doctors, dentists and pharmacists who treat you that you are taking
this medicine.

If you are going to have any surgery or procedure, including dental surgery, tell
your surgeon, doctor or dentist that you are taking this medicine.

Eliquis should be temporarily stopped before surgery.

Your doctor will tell you when to stop using Eliquis before your surgery or procedure.

Your doctor will also tell you when you can start taking Eliquis after your surgery.

Tell your doctor that you are taking Eliquis if your doctor is planning for you to
have an anaesthetic injection in your back (spinal or epidural injection).

If you become pregnant while taking this medicine, tell your doctor immediately.

If you are about to have any blood tests, tell your doctor that you are taking this
medicine.

It may interfere with the results of some tests.

Keep all of your doctor’s appointments so that your progress can be checked.

Things you must not do

Do not take Eliquis to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as
you.

Do not stop taking your medicine or lower the dosage without first checking with your
doctor.

If you stop taking it suddenly, your condition may worsen or you may have serious
side effects.

Things to be careful of

Eliquis contains lactose. If you have been told by your doctor that you have an intolerance
to some sugars, contact your doctor before taking it.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you
are taking Eliquis.

All medicines can have side effects. Sometimes they are serious, most of the time
they are not. You may need medical attention if you get some of the side effects.

It can be difficult to tell whether side effects are the result of taking Eliquis,
effects of your condition or side effects of other medicines you may be taking. For
this reason it is important to tell your doctor of any change in your condition.

Do not be alarmed by the list of side effects.

You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if…

Tell your doctor or pharmacist if you notice any of the following and they worry you:

tiredness, weakness, paleness, dizziness, light-headedness, headache – which can be
due to low iron in the blood

bleeding from any part of your body, no matter how minor, as these may be difficult
to control

bruising

nausea (feeling sick), vomiting

diarrhoea or constipation

fever

sore nasal passages and throat

frequent need to urinate or pain while urinating

coughing.

The above list includes the more common side effects of your medicine.

Tell your doctor as soon as possible if…

Tell your doctor as soon as possible if you notice any of the following:

excessive bleeding or prolonged bleeding. There is no antidote to reverse this bleeding.
It is important to contact your doctor immediately if you experience excessive or
prolonged bleeding.

stomach swelling, yellowing of the skin or whites of the eyes (due to liver problems)

oozing from your surgical wound

swelling of the hands, ankles or feet due to water retention.

The above list includes serious side effects that may require medical attention.

Go to hospital if…

Tell your doctor immediately or go to the Accident and Emergency Department at your
nearest hospital, if you notice any of the following:

bleeding from your nose

if you have dark brown urine or blood in your urine

if you cough up blood

if you vomit and it is black

if you have black stools or blood in your stools

excessive bleeding or prolonged bleeding. There is no antidote to reverse this bleeding.
It is important to contact your doctor immediately if you experience excessive or
prolonged bleeding.

if you have an allergic reaction to Eliquis. Symptoms may include shortness of breath,
wheezing or difficulty breathing, swelling of the face, lips, tongue or other parts
of the body, rash, itching or hives on the skin.

The above list includes very serious side effects. You may need urgent medical attention
or hospitalisation.

Tell your doctor or pharmacist if you notice anything else that is making you feel
unwell.

Other side effects not listed above may also occur in some people.

Some of the other possible side effects (for example, changes in liver function) can
only be found when your doctor does tests from time to time to check your progress.

After taking Eliquis

Storage

Keep your tablets in the pack until it is time to take them.

If you take the tablets out of the pack they may not keep well.

Keep your tablets in a cool dry place where the temperature stays below 30°C.

Do not store Eliquis or any other medicine in the bathroom or near a sink. Do not
leave it on a window sill or in the car.

Heat and dampness can destroy some medicines.

Keep it where children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place
to store medicines.

Disposal

If your doctor tells you to stop taking this medicine or the expiry date has passed,
ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

Eliquis 2.5 mg tablets are yellow and round with “893” on one side and “2 1/2” on
the other.

They are packed in blister packs in cartons of 10, 14, 20, 30, 60 or 100 tablets.

Eliquis 5 mg tablets are pink and oval-shaped with “894” on one side and “5” on the
other.

They are packed in blister packs in cartons of 14, 20, 28, 56, 60, 100, 112, 120 and
168 tablets.

Not all pack sizes may be available.

Ingredients

Eliquis tablets contain 2.5 mg or 5 mg of apixaban as the active ingredient.

They also contain:

lactose

lactose monohydrate

microcrystalline cellulose

croscarmellose sodium

sodium lauryl sulfate

magnesium stearate

hypromellose

titanium dioxide

glycerol triacetate

yellow iron oxide (2.5 mg tablets)

red iron oxide (5 mg tablets)

This medicine does not contain sucrose, gluten, tartrazine or any other azo dyes.

Sponsored and Supplied by:

Bristol-Myers Squibb Australia Pty Ltd

4 Nexus Court

Mulgrave VIC 3170

Toll free number: 1800 067 567

Also distributed by:

Pfizer Australia Pty Ltd

Sydney NSW

Toll Free Number: 1800 675 229

Australian registration numbers

2.5 mg tablet: AUST R 172244

5 mg tablet: AUST R 193474

Date of preparation

This leaflet was prepared in June 2020.

® ELIQUIS is a registered trademark of Bristol-Myers Squibb Company.

© Copyright of Bristol-Myers Squibb Company 2019.

What You Need to Know — Dr. AFib™

Anticoagulants or “blood thinners” are commonly prescribed for the treatment of atrial fibrillation (AFib). Several blood thinners have been found to significantly reduce the risk of stroke in patients with atrial fibrillation. One of the most commonly prescribed blood thinning medications for AFib patients is Eliquis (apixaban).

I have prescribed Eliquis for many of my patients and have found it to be very beneficial for stroke risk reduction. However, like any medication, you may experience side effects when taking Eliquis.

Here’s a look at how Eliquis works, some common and less common side effects, and some ways that those side effects can be managed with help from your doctor.

A Brief History of Eliquis

Eliquis (apixaban) was first approved by the US Food and Drug Administration (FDA) on December 28, 2012. This was based on the results of the ARISTOTLE clinical trial in 2011.

The ARISTOTLE trial looked at 18,000 patients and compared Eliquis with another anticoagulant, Coumadin (warfarin). The patients taking Eliquis were found to have fewer strokes than those taking Coumadin, and a lower rate of major bleeding.

After this trial, the FDA approved Eliquis to help prevent blood clots caused by AFib that isn’t due to a heart valve problem.

How Does Eliquis Work?

Your liver makes many different types of enzymes to regulate different processes in your body. Some of these enzymes work together with platelets in your blood to make your blood clot.

An enzyme called factor Xa (FXa) is one that plays a key role in making the substances that make up blood clots.

If you have a condition (such as AFib) where your body might make unwanted blood clots, your doctor may prescribe a medication like Eliquis to help prevent these clots.

Eliquis works by partially preventing factor Xa from doing its job. This means your body is less likely to form blood clots.

What Are The Most Common Side Effects of Eliquis?

Since Eliquis reduces your body’s ability to make blood clots it’s not surprising that many of the unwanted effects of Eliquis involve bleeding.

Some common bleeding-related side effects of Eliquis include:

●      Bruising easily

●      More bleeding than usual (even from small cuts)

●      Nosebleeds

●      Bleeding gums

●      Heavier menstrual periods

●      Anemia

●      Blood in the urine

Other common side effects that were reported:

●      Nausea

●      Vomiting

●      Indigestion

●      Headache

●      Fatigue

●      Cough

This isn’t a complete list of every possible side effect and everyone reacts to medication differently. If you think that you are experiencing a side effect from your Eliquis (even if it’s not on the list) make sure to report it to your doctor.

WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS, (B) SPINAL/EPIDURAL HEMATOMA

(A) Premature discontinuation of any oral anticoagulant, including ELIQUIS^® (apixaban), increases the risk of thrombotic events. If anticoagulation with ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant.

(B) Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:

• use of indwelling epidural catheters
• concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants
• a history of traumatic or repeated epidural or spinal punctures
• a history of spinal deformity or spinal surgery
• optimal timing between the administration of ELIQUIS and neuraxial procedures is not known

Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary.

Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated.

CONTRAINDICATIONS

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

WARNINGS AND PRECAUTIONS

• Increased Risk of Thrombotic Events after Premature Discontinuation: Premature discontinuation of any oral anticoagulant, including 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 atrial fibrillation patients. If ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, 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 antiplatelet agents, other anticoagulants, heparin, thrombolytic agents, SSRIs, SNRIs, and NSAIDs.
  • Advise patients of signs and symptoms of blood loss and to report them immediately or go to an emergency room. Discontinue ELIQUIS in patients with active pathological hemorrhage.
  • The anticoagulant effect of apixaban can be expected to persist for at least 24 hours after the last dose (i.e., about two half-lives). An agent to reverse the anti-factor Xa activity of apixaban is available. Please visit www.andexxa.com for more information on availability of a reversal agent.
• Spinal/Epidural Anesthesia or Puncture: Patients treated with ELIQUIS undergoing spinal/epidural anesthesia or puncture may develop an epidural or spinal hematoma which can result in long-term or permanent paralysis. The risk of these events may be increased by the postoperative use of indwelling epidural catheters or the concomitant use of medicinal products affecting hemostasis. Indwelling epidural or intrathecal catheters should not be removed earlier than 24 hours after the last administration of ELIQUIS. The next dose of ELIQUIS should not be administered earlier than 5 hours after the removal of the catheter. The risk may also be increased by traumatic or repeated epidural or spinal puncture. If traumatic puncture occurs, delay the administration of ELIQUIS for 48 hours. Monitor patients frequently and if neurological compromise is noted, urgent diagnosis and treatment is necessary. Physicians should consider the potential benefit versus the risk of neuraxial intervention in ELIQUIS patients.
• Prosthetic Heart Valves: The safety and efficacy of ELIQUIS have not been studied in patients with prosthetic heart valves and is not recommended in these patients.
• Acute PE in Hemodynamically Unstable Patients or Patients who Require Thrombolysis or Pulmonary Embolectomy: Initiation of ELIQUIS is not recommended as an alternative to unfractionated heparin for the initial treatment of patients with PE who present with hemodynamic instability or who may receive thrombolysis or pulmonary embolectomy.
• Increased Risk of Thrombosis in Patients with Triple Positive Antiphospholipid Syndrome (APS): Direct-acting oral anticoagulants (DOACs), including ELIQUIS, are not recommended for use in patients with triple-positive APS. For patients with APS (especially those who are triple positive [positive for lupus anticoagulant, anticardiolipin, and anti–beta 2-glycoprotein I antibodies]), treatment with DOACs has been associated with increased rates of recurrent thrombotic events compared with vitamin K antagonist therapy.

ADVERSE REACTIONS

• The most common and most serious adverse reactions reported with ELIQUIS were related to bleeding.

TEMPORARY INTERRUPTION 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. Bridging anticoagulation during the 24 to 48 hours after stopping ELIQUIS and prior to the intervention is not generally required. ELIQUIS should be restarted after the surgical or other procedures as soon as adequate hemostasis has been established.

DRUG INTERACTIONS

• Combined P-gp and Strong CYP3A4 Inhibitors: Inhibitors of P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4) increase exposure to apixaban and increase the risk of bleeding. For patients receiving ELIQUIS doses of 5 mg or 10 mg twice daily, reduce the dose of ELIQUIS by 50% when ELIQUIS is coadministered with drugs that are combined P-gp and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, or ritonavir). In patients already taking 2.5 mg twice daily, avoid coadministration of ELIQUIS with combined P-gp and strong CYP3A4 inhibitors. Clarithromycin Although clarithromycin is a combined P-gp and strong CYP3A4 inhibitor, pharmacokinetic data suggest that no dose adjustment is necessary with concomitant administration with ELIQUIS.
• Combined P-gp and Strong CYP3A4 Inducers: Avoid concomitant use of ELIQUIS with combined P-gp and strong CYP3A4 inducers (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. APPRAISE-2, a placebo-controlled clinical trial of apixaban in high-risk post-acute coronary syndrome patients treated with aspirin or the combination of aspirin and clopidogrel, was terminated early due to a higher rate of bleeding with apixaban compared to placebo.

PREGNANCY

• The limited available data on ELIQUIS use in pregnant women are insufficient to inform drug-associated risks of major birth defects, miscarriage, or adverse developmental outcomes. Treatment may increase the risk of bleeding during pregnancy and delivery, and in the fetus and neonate.
  • Labor or delivery: ELIQUIS use during labor or delivery in women who are receiving neuraxial anesthesia may result in epidural or spinal hematomas. Consider use of a shorter acting anticoagulant as delivery approaches.

LACTATION

• Breastfeeding is not recommended during treatment with ELIQUIS.

FEMALES AND MALES OF REPRODUCTIVE POTENTIAL

• Females of reproductive potential requiring anticoagulation should discuss pregnancy planning with their physician. The risk of clinically significant uterine bleeding, potentially requiring gynecological surgical interventions, identified with oral anticoagulants including ELIQUIS should be assessed in these patients and those with abnormal uterine bleeding.

Indications

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

ELIQUIS is indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery.

ELIQUIS is indicated for the treatment of DVT and PE, and to reduce the risk of recurrent DVT and PE following initial therapy.

Please see U.S. FULL PRESCRIBING INFORMATION, including Boxed WARNINGS, and MEDICATION GUIDE.

ELIQUIS is available in 2.5 mg and 5 mg tablets.

Apixaban (Eliquis®) to treat blood clots

Overview | Schedule | Side Effects | Monitoring | Tips | Patient Assistance | References

Apixaban (Eliquis®) is a Supportive Care Therapy to prevent or treat Blood Clots

How does apixaban (Eliquis®) work?
Apixaban is designed to help your body eliminate blood clots by blocking the action of a specific clotting factor known as Factor Xa (“factor ten-A”).

By blocking clotting Factor Xa, your body breaks down the clot faster than it can build it. This is known as anticoagulation treatment.

Goals of therapy:
Apixaban is taken to treat large blood clots that are harmful to your body, for example: those in the lungs, heart, or brain, or those that cause swelling or pain in the arms or legs.

Apixaban (Eliquis®) is available by doctor’s prescription only.

Schedule

Usual apixaban (Eliquis®) starting dose to treat a blood clot in the veins (Deep-Vein Thrombosis, DVT) or lungs (Pulmonary Embolism, PE):

• Apixaban 10 mg (two 5 mg oral tablets) by mouth twice daily for 7 consecutive days, then
• Apixaban 5 mg oral tablet by mouth twice daily continuously
  • Apixaban may be taken with or without food

If you miss a morning dose, take the missed dose as soon as possible on the same day, and resume taking apixaban at your normal time in the evening. Do not double the dose to make up for the missed dose. If you miss the evening dose, resume the normal dosing schedule in the morning the following day.

It can take a long time for your body to break down and get rid of a blood clot.

• Most cancer patients who develop a clot are treated 3 to 6 months
• May be continued until cancer is gone
• Your doctor may recommend apixaban with no stopping point

For patients taking apixiban without an end date, after at least 6 months of therapy, your doctor may decide to reduce the dose of apixaban to 2.5 mg by mouth twice daily depending upon your history of clots, ongoing risk factors for blood clots, whether you are having side effects from apixaban, as well as other medications you are taking.

Do not run out of apixaban tablets. Be sure to refill your prescription before you take your last pill. If you stop taking apixaban (Eliquis®) before your doctor says that it is okay to stop taking it, there may be an increased risk of the blood clot getting worse or increased risk of developing new blood clots. Talk to your doctor before suddenly discontinuing apixaban therapy.

Note: Your doctor may choose to shorten or lengthen the amount of time you stay on therapy due to certain factors specific to your case based upon the perceived risks and benefits.

Side Effects

In the prescribing label information (apixaban package insert), the most commonly reported side effects from apixaban (Eliquis®) are shown here. The exact percentages of patients that will experience apixaban side effects is unknown because it has been used under a wide variety of patient populations in many different clinical trials:

A note about side effect percentages

• Any type of bleeding (11 – 15%)*
• Nose bleed (3 – 4%)
• Blood in urine (2%)
• Bruising (2%)
• Bleeding from gums (1%)
• Rectal bleeding (1%)
• Coughing up blood (1%)
• For women, excessive bleeding during menstrual cycle (1%)
• Bleeding into muscles (1%)
• Bleeding in the stomach or intestines (less than 1%)
  • black or tarry stools
  • bright red blood in stools

• Bleeding underneath the skin (less than 1%)
• Blood in vomit (less than 1%)
• Low red blood cells [anemia] from bleeding (less than 1%)

*In clinical trials, 9 – 12% of patients had a bleeding event that was considered a minor bleed, 3 – 4% had a non-major bleeding event, but did require hospitalization or evaluation by a doctor, and less than 1% had a bleed that was considered a major or life threatening bleeding event.

If you have any signs of bleeding while taking apixaban, you should call your doctor immediately or go to an emergency room.

Apixaban should be used in pregnant women only if the potential benefits to the mother outweigh the potential risks to the unborn baby. Treatment may increase the risk of bleeding in both the mother and the baby, and increase the risk of bleeding during delivery. Additionally, it is unknown if apixaban is excreted in human breast milk, therefore women should either discontinue breastfeeding or discontinue using apixaban.

Importantly, not all people who experience a side effect from Eliquis® (apixaban) will experience it in the same way. It may be mild in some or severe in others, depending upon the individual. Everybody is different. Additionally, side effects may vary over time. For some, side effects may be a reason to delay or switch treatment, reduce the dose, or avoid future treatment with a certain medication altogether.

After starting treatment with Eliquis® (apixaban), be sure to come back and watch all of the side effect videos shown below. Each of these videos contain valuable information about side effect management that will hopefully help you to both feel better and stay out of the hospital.

Side effect videos

BleedingBlood Clots

Monitoring

How often is monitoring needed?
Labs (blood tests) may be checked before treatment and periodically during treatment until stable. Labs often include: Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), or basic metabolic panel (BMP), plus any others your doctor may order.

How often is imaging needed?
Imaging is checked before treatment to diagnose the presence of a blood clot. Imaging may include: computerized tomography angiography (CT angiogram or CTA) scans, ventilation/perfusion (VQ) scan, or ultrasounds of arms or legs (also known as venous dopplers). Typically, if a blood clot is found on any of the above imaging techniques, it is not routinely repeated after starting therapy to see if the blood clot has gone away.

Other imaging such as magnetic resonance imaging (MRI) or computerized tomography (CT) scans may be checked during treatment if there is a concern for bleeding into certain organs or tissues.

How might blood test results/imaging affect treatment?
Depending upon the results, your doctor may advise to continue apixaban as planned, reduce the dose of future treatments, delay the next dose until the side effect goes away, or switch to an alternative therapy.

Note: Clotting tests such as the prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (aPTT) are not useful for monitoring the anticoagulant effect of apixaban.

Questions to Ask Your…

A better understanding of your treatments will allow you to ask more questions of your healthcare team. We then hope that with the answers, you will get better results and have greater satisfaction with your care. Because we know it’s not always easy to know what questions to ask, we’ve tried to make it easy for you!

Choose any healthcare provider below to see common questions that you may want to ask of this person. Then, either print each list to bring to your clinic visits, or copy the questions and send them as a message to your healthcare team through your electronic medical record.

ChemoExperts Tips

• You may bruise more easily and it may take longer to stop bleeding from simple cuts and scrapes
• Tell your dentist that you are taking apixaban in order to prevent excessive bleeding during dental procedures
• Apixaban may need to be temporarily held before and after a surgery or invasive procedure if their is a risk of bleeding. It may also need to be temporarily held to reduce the risk of bleeding if your platelet count is too low 
• Tell your doctor if you have a known bleeding disorder before you start treatment with apixaban
• If you have trouble swallowing apixaban tablets, they may be crushed and mixed with apple juice, applesauce, or water and swallowed immediately. Mix the crushed tablets in a small amount of liquid or applesauce to be sure that you can swallow the whole dose
• The risk of a spinal hematoma (fluid collection made up of blood) in patients taking apixaban may be increased during a lumbar pucture (spinal tap). Tell your doctor and pharmacist that you are taking apixaban before a lumbar puncture is performed so that you can discuss if temporarily holding apixaban therapy (miss one or more doses) before or after the procedure would reduce the risk of bleeding
• Talk to your doctor or pharmacist before taking any over-the-counter (OTC) pain medications such as ibuprofen (Advil® or Motrin®), naproxen (Aleve®), and aspirin as these medications can increase the risk of bleeding when taken with apixaban. Apixaban is NOT usually taken with other anticoagulants
• Certain antidepressants such as “Selective Serotonin Reuptake Inhibitors, or SSRIs”, or antiplatelet medications such as clopidogrel (Plavix®) can increase the risk of bruising or bleeding when taken with apixaban
• May interact with certain antifungal, antiviral, and seizure medications that may either increase the blood levels of apixaban and increase risk of bleeding or decrease blood levels and decrease the effectiveness of apixaban
• Store apixaban (Eliquis®) at room temperature between 68°F to 77°F
• A pharmacist should ALWAYS review your medication list to ensure that drug interactions are prevented or managed appropriately. When taken with certain medications, the dose of apixaban may need to be decreased to prevent bruising or bleeding

Patient Assistance & Co-payment Coverage

Patients under the age of 65 years, or those with private insurance plans:
If you have insurance and are looking for patient assistance or copay assistance for Apixaban (Eliquis®), we have provided links that may help.

Visit our Patient Assistance page and click the links to various patient assistance programs for help paying for Apixaban (Eliquis®). Depending upon your income, they may be able to help cover the cost of:

For Branded medications (may be available for generic medications too), check with the manufacturer to determine if a co-pay card is offered and if it could reduce your monthly copay.

• If you are uninsured, check with the manufacturer to determine if you are eligible to receive medication at no cost.

Medicare and Medicaid patients (Patients 65 years or older):
The clinic providing treatment will likely pre-authorize medications and immune therapies such as Apixaban (Eliquis®) and are the best source to help you understand drug cost.

• Ask to speak with a patient assistance technician or financial counselor at the clinic or hospital administering this therapy.

Eliquis tab. p / pl. about. 2.5mg No. 20 – instructions for use, description, contraindications, side effects, overdose, composition

Risk of bleeding

As with other anticoagulants, patients receiving Eliquis ^® should be closely monitored for signs of bleeding. In conditions with a high risk of bleeding, the drug is recommended to be used with caution. The use of the drug Eliquis ^® should be discontinued if severe bleeding develops.

Although apixaban therapy does not require constant monitoring of its concentration in the blood, it may sometimes be advisable to conduct a calibrated quantitative analysis of anti-Xa-factor activity in those exceptional cases where data on the effects of apixaban can facilitate clinical decision-making, for example, in case of overdose and emergency surgery. intervention.

Interaction with other drugs affecting hemostasis

Due to the high risk of bleeding, simultaneous use with any other anticoagulants is contraindicated.

The simultaneous use of Eliquis ^® with antiplatelet agents increases the risk of bleeding.

Care must be taken with the simultaneous use of Eliquis ^® with selective serotonin reuptake inhibitors and serotonin and norepinephrine (norepinephrine) reuptake inhibitors.

After surgery, it is not recommended to use other platelet aggregation inhibitors simultaneously with Eliquis ^® .

In patients with atrial fibrillation and conditions requiring antiplatelet therapy with one or two drugs, it is necessary to conduct a thorough assessment of the ratio of potential benefits and risks before starting concomitant therapy with Eliquis ^® .

In a clinical study involving patients with atrial fibrillation, the simultaneous use of ASA led to an increased risk of major bleeding both while taking apixaban and while taking warfarin.In this clinical study, combination therapy with two antiplatelet agents was rarely used.

The use of thrombolytic agents for the treatment of acute ischemic stroke

Experience with the use of thrombolytic agents for the treatment of acute ischemic stroke in patients receiving apixaban is very limited.

Patients with artificial heart valves

The safety and efficacy of the drug in patients with artificial heart valves with and without atrial fibrillation has not been studied.The use of Eliquis ^® is not recommended for this group of patients.

Surgical and invasive procedures

The use of Eliquis ^® should be discontinued at least 48 hours before a planned surgery or invasive procedure with a moderate or high risk of bleeding. This includes interventions in which the likelihood of clinically significant bleeding is not excluded or for which the risk of bleeding is unacceptable.

The use of Eliquis ^® should be discontinued at least 24 hours before a planned surgery or invasive procedure with a low risk of bleeding.This includes interventions for which minimal, non-localized, or easily controlled bleeding is expected.

If an operation or invasive procedure cannot be postponed, it should be carried out with appropriate caution, given the increased risk of bleeding. The risk of bleeding should be correlated with the need for emergency intervention. Nonvalvular atrial fibrillation usually does not require the use of “bridge therapy” for 24-48 hours after discontinuation of apixaban before surgery.

After an invasive procedure or surgery, the use of Eliquis ^® should be resumed as soon as possible, provided that the clinical situation permits and sufficient hemostasis has been established (for information on cardioversion, see the Dosage Regimen section).

In patients with atrial fibrillation, there is no need to discontinue therapy with Eliquis ^® before catheter ablation.

Temporary cessation of therapy

Discontinuation of anticoagulants, including Eliquis ^® , due to active bleeding, elective surgery or invasive procedure increases the patient’s risk of thrombosis.Interruptions in treatment should be avoided, and if for any reason a temporary cessation of anticoagulant therapy with Eliquis ^® is required, it should be resumed as soon as possible.

Treatment of DVT and PE

It is not recommended to replace therapy with unfractionated heparin with Eliquis ^® during the initiation of therapy in patients with pulmonary embolism with unstable hemodynamics, possible thrombolysis or pulmonary artery thrombectomy, i.e.because the safety and efficacy of apixaban in these clinical situations have not been established.

Patients with cancer

The efficacy and safety of apixaban in the treatment of DVT, the treatment of PE and the prevention of recurrent DVT and PE (rVTE) in patients with actively progressive malignant neoplasm have not been established.

Patients with renal failure

Limited clinical data show that in patients with severe renal impairment (CC 15–29 ml / min), plasma apixaban concentrations increase, which may increase the risk of bleeding.For the treatment of DVT, the treatment of PE and the prevention of recurrent DVT and PE (rVTE), apixaban in patients with severe renal impairment (CC 15–29 ml / min) should be used with caution.

For the prevention of stroke and systemic embolism in patients with NFP, patients with severe renal impairment (CC 15-29 ml / min) and patients with serum creatinine levels ≥1.5 mg / dL (133 μmol / L) in combination with age ≥80 years or body weight ≤60 kg, the dose of apixaban should be reduced to 2.5 mg 2 times / day.

Due to the lack of experience in the clinical use of apixaban in patients with CC <15 ml / min or on dialysis, apixaban is not recommended in this group of patients.

Elderly patients

The risk of bleeding may increase with age.

Also, the simultaneous use of Eliquis ^® and ASA in elderly patients requires caution due to the potentially higher risk of bleeding.

Body weight

With low body weight (<60 kg), the risk of bleeding may increase.

Patients with hepatic impairment

Eliquis ^® is contraindicated in patients with liver disease associated with coagulopathy and a clinically significant risk of bleeding.

The drug is not recommended for patients with severe liver dysfunction.

The drug should be used with caution in patients with mild to moderate hepatic impairment (stage A or B according to Child-Pugh classification).

Patients with elevated liver enzymes ALT / AST> 2 × ULN or total bilirubin ≥ 1.5 × ULN were excluded from clinical trials. Therefore, in this population, the drug Eliquis ^® should be used with caution. Before using the drug Eliquis ^® , it is necessary to check the biochemical parameters of the liver function.

Interaction with cytochrome inhibitors P 450 and inhibitors P-glycoprotein

It is not recommended to use the drug Eliquis ^® in patients receiving concomitant systemic treatment with potent inhibitors of the isoenzyme CYP3A4 and P-glycoprotein, such as antimycotics of the azole group (for example, ketoconazole, itraconazole, voriconazole and posaconazole) and HIV protease inhibitors (for example) …These drugs can increase apixaban exposure by 2 times or more in the presence of additional factors that also increase apixaban exposure (eg, severe renal impairment).

Interaction with isoenzyme inducers CYP 3 A 4 and P-glycoprotein

The simultaneous use of Eliquis ^® with powerful inducers of the isoenzyme CYP3A4 and inducers of P-glycoprotein (for example, rifampicin, phenytoin, carbamazepine, phenobarbital and St. John’s wort preparations) can also lead to a decrease in the concentration of apixaban in blood plasma (approximately 50%).In a clinical study involving patients with atrial fibrillation, a decrease in efficacy and an increased risk of bleeding were noted with the simultaneous use of apixaban and powerful inducers of the isoenzyme CYP3A4 and P-glycoprotein compared with the use of apixaban as monotherapy.

The following recommendations apply to patients receiving systemic therapy with potent inhibitors of the isoenzyme CYP3A4 and P-glycoprotein:

• for the prevention of venous thromboembolism in patients after planned hip or knee arthroplasty, for the prevention of stroke and systemic thromboembolism in non-valvular atrial fibrillation, as well as for the prevention of recurrence

Eliquis (an apixaban brand in 2020) was recognized as the Best Prescription Brand in Russia in 2020 according to IQVIA RX AWARDS

According to the research of PharmaTrend company IQVIA , drug “Eliquis” (apixaban) of the company Pfizer for the period from July 2019.to June 2020 showed the largest increase in sales in absolute terms among the Rx drugs in the retail segment on the Russian market. Sales of the drug in the reporting period increased by 46%.

Eliquis® (apixaban) is an oral selective coagulation factor Xa inhibitor used for the prevention of stroke and systemic thromboembolism in adult patients with nonvalvular atrial fibrillation, as well as for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and the prevention of venous embolism thromboembolism in patients after elective hip or knee arthroplasty.

According to the international randomized clinical trial ARISTOTLE, apixaban is the only oral anticoagulant (OAC) that surpassed warfarin in patients with nonvalvular atrial fibrillation in three parameters: efficacy (reduced risk of stroke and systemic embolism), safety and lower risk of bleeding) reduction in overall mortality ^[1] . In 2019, this study was ranked among the prestigious Most Outstanding Publications by New England Journal of Medicine editor-in-chief Dr. Jeffrey Drazen, The Drasen Dozen: Papers that Changed Clinical Practice Since 2000 [2].

“ I am sincerely glad that Eliquis was named the number one drug *. The drug has established itself both in the world in clinical practice and in Russia, effectively helping to reduce the risk of stroke and systemic thromboembolism, treat deep vein thrombosis and pulmonary embolism. The availability of innovative treatment methods is very important for patients as it allows them not only to avoid disability, but also to stay alive. “, commented Maria Ananyeva, Sales and Marketing Director, Pfizer’s Innovative General Therapy Business, .

The efficacy and safety of apixaban has been confirmed in large international randomized clinical trials (ADVANCE-1,2,3, AMPLIFY, AMPLIFY-EXT, ARISTOTLE, AVERROES, AUGUSTUS), which involved tens of thousands of patients. The results of these trials allowed the drug to be registered in many countries.

In the largest European clinical practice analysis of data on the efficacy and safety of NAXOS POAC [3] and in the American real-life study involving almost half a million patients with atrial fibrillation ARISTOPHANES [4], apixaban demonstrated efficacy and safety advantages over both warfarin and a number of parameters over other POACs (rivaroxaban and dabigatran).

IQVIA is a world leader in using data, technology, advanced analytics and expertise to advance healthcare and improve the quality of life for people. PharmaTrend research is an audit of drug sales from pharmacies, which reflects the real preferences of consumers. The leaders in the Rx segment of the retail pharmaceutical market in Russia have been awarded for the second year in a row.

* among Rx drugs in the retail segment on the Russian market according to IQVIA data.Absolute Revenue growth PharmaTrand MAT 06/2020

Pfizer: Advanced Solutions that Change Patient Lives

Through innovation and global resources, Pfizer works to improve the health and well-being of people at every stage of life. We strive to set high standards for the quality and safety of our research, development and production of medicines. The company’s product portfolio includes pharmaceuticals, including vaccines.

Every day, Pfizer employees work in developed and developing countries to improve prevention and treatment of today’s most serious diseases. In keeping with our commitment as one of the world’s leading biopharmaceutical companies, Pfizer works with healthcare professionals, government agencies and local communities to ensure and expand the availability of reliable, quality healthcare worldwide.

For 170 years, Pfizer has worked to improve the lives of those who count on us.

www.pfizer.ru

Also, to learn more about the company, you can subscribe to our pages on the social networks VKontakte and Instagram

PP-PFE-RUS-0242

Actual on 07.10.2020

Brief information about Eliquis®.

INN: apixaban

Dosage form: film-coated tablets.

Composition: one tablet contains 2.5 mg and 5 mg apixaban.

Indications for use

· Prevention of venous thromboembolism in patients after elective hip or knee arthroplasty.

Prevention of stroke and systemic thromboembolism in adult patients with nonvalvular atrial fibrillation who have one or more risk factors (such as a history of stroke or transient ischemic attack, age 75 and older, arterial hypertension, diabetes mellitus, accompanied by symptoms of chronic heart failure ( functional class II and higher according to NYHA classification).The exception is patients with severe to moderate mitral stenosis or artificial heart valves.

· Treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), as well as prevention of recurrence of DVT and PE.

Contraindications

Hypersensitivity to apixaban or any other component of the drug. Active clinically significant bleeding. Diseases of the liver, accompanied by disorders in the blood coagulation system and a clinically significant risk of bleeding.Diseases or conditions characterized by a significant risk of major bleeding: current or recent exacerbation of gastrointestinal ulcer; the presence of a malignant neoplasm with a high risk of bleeding; recent damage to the brain or spinal cord; recently undergone surgery on the brain or spinal cord, as well as on the organ of vision; recent hemorrhagic stroke; established or suspected varicose veins of the esophagus; arteriovenous malformation; vascular aneurysm or pronounced intraspinal or intracerebral vascular changes.Renal dysfunction with creatinine clearance less than 15 ml / min, as well as use in patients on dialysis. Age up to 18 years (no data on the use of the drug). Pregnancy (there are no data on the use of the drug). Breastfeeding period (no data on the use of the drug). Simultaneous use with any other anticoagulant drugs, including unfractionated heparin (UFH), low molecular weight heparins (LMWH) (enoxaparin, dalteparin, etc.), heparin derivatives (fondaparinux, etc.)), oral anticoagulants (warfarin, rivaroxaban, dabigatran, etc.), except for those situations when the patient is transferred to therapy or from therapy with apixaban or if unfractionated heparin is prescribed in doses necessary to maintain patency of the central venous or arterial catheter. Congenital lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

Side effects

Frequent adverse reactions were bleeding (epistaxis, gastrointestinal, rectal, bleeding from the gums, hematuria, hemorrhage in the tissue of the eyeball), bruising, hematoma, anemia, closed trauma, nausea.A list of all side effects is presented in the full version of the instructions for medical use.

Method of administration and dosage

The drug Eliquis ^® is taken orally, regardless of food intake.

For patients who cannot swallow the tablet whole, it can be crushed and diluted (in water, aqueous dextrose, apple juice or puree) and swallowed immediately. Alternatively, the tablet can be crushed and diluted in water or 5% aqueous dextrose and the resulting suspension is immediately administered via a nasogastric tube.The drug substance in crushed tablets is stable in water, aqueous dextrose, apple juice or puree for up to 4 hours.

In patients with atrial fibrillation : 5 mg twice a day.

In patients with atrial fibrillation, the dose of the drug is reduced to 2.5 mg twice a day in the presence of a combination of two or more of the following characteristics – age 80 years and older, body weight 60 kg or less, or plasma creatinine concentration ≥ 1.5 mg / dl (133 μmol / l).

In patients with severe renal impairment (with creatinine clearance 15-29 ml / min) and atrial fibrillation, a dose of apixaban should be used – 2.5 mg twice a day.

For non-anticoagulated patients with atrial fibrillation who require cardioversion, to achieve anticoagulation, it is possible to prescribe at least 5 doses of the drug, 5 mg 2 times a day (2.5 mg per day if the patient meets the dose reduction criteria) before the procedure.If cardioversion is required before the appointment of 5 doses of Eliquis, a loading dose of apixaban 10 mg may be used at least 2 hours before the procedure, followed by 5 mg 2 times a day (2.5 mg per day if the patient meets the dose reduction criteria) …

In patients after planned hip or knee arthroplasty : 2.5 mg 2 times a day (first dose 12-24 hours after surgery).In patients who have undergone hip arthroplasty, the recommended duration of therapy is 32 to 38 days, and the knee joint is 10 to 14 days.

Treatment of deep vein thrombosis, pulmonary embolism (PE):

10 mg twice a day for 7 days, then 5 mg 2 times a day.

The duration of treatment is determined individually, taking into account the ratio of the expected benefit and the risk of clinically significant bleeding.

Prevention of recurrent deep vein thrombosis, pulmonary embolism (PE):

2.5 mg twice daily after at least 6 months of treatment for deep vein thrombosis or PE.

Dispensed by prescription.

Expiration date: 3 years.

Registration certificate: LP-002007, LP-001475

Detailed information is contained in the Instructions for medical use of the medicinal product; before use, you must read the full text of the Instructions.

[1] Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation.N Engl J Med. 2011 Sep 15; 365 (11): 981-92.

[2] Drazen’s Dozen: articles that changed practice since 2000. The New England Journal of Medicine https://cdn.nejm.org/pdf/Drazens-Dozen.pdf

[3] Steg P.G. Apixaban in the prevention of stroke and systemic embolism in patients with atrial fibrillation in real-life setting in France SNIIRAM study. Presented at the European Society of Cardiology 2019 Congress. September 1, 2019; Abstract 1362.

[4] Lip GYH et al.Effectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation Patients // Stroke. 2018 Dec; 49 (12): 2933-2944.

Essentiale Forte N – side effects, contraindications, mechanism of action

1. Vovk E. Treatment of non-alcoholic fatty liver disease in the practice of a therapist: what: where? when? // RMJ. 2011. Vol. 19, No. 15. P. 914-922.

2.V. T. Ivashkin et al. Clinical guidelines for the diagnosis and treatment of non-alcoholic fatty liver disease of the Russian Society for the Study of the Liver and the Russian Gastroenterological Association. RZHGGK 2 (2016), 24 – 42.

3. Gundermann K.-J. et al. Activity of essential phospholipids (EPL) from soybean in liver diseases. // Pharmacol. Rep. 2011. Vol. 63, No. 3. P. 643–659.

4. Instructions for use Essentiale ^® Forte N.

5. Kuntz, E., Kuntz, H., Hepatology: Principles and Practice, second edition. Springer Medizin Verlag, Heidelberg, Germany. 2006, 906 pages.

6. Gundermann et al. Essential phospholipids in fatty liver: a scientific update. Clin Exp Gastroenterol 2016; 9: 105-117.

7. E. Sas et al. Beneficial influence of polyunsaturated phosphatidylcholine enhances functional liver condition and liver structure in patients with nonalcoholic steatohepatitis.Results of prolonged randomized blinded prospective clinical study. Journal of Hepatology 2013 vol. 58, S. 549. Abstract is only available.

8. Gonciarz Z et al. Randomized placebo-controlled double trial on ‘essential’ phospholipids in the treatment of fatty liver associated with diabetes. Med. Chir. Digest. 1988, 17, 61 – 85.

9. Narendra S. Choudhary et al. Rapid Reversal of Liver Steatosis With Life Style Modification in Highly Motivated Liver Donors.J Clin Exp Hepatol. 2015 Jun; 5 (2): 123-126.

10. Lazebnik LB Non-alcoholic fatty liver disease: clinical picture, diagnosis, treatment (recommendations for therapists, 2nd version), Therapy 2017 (3), 6 – 23.

11. Yin D, Kong L. Observation for curative effect of Essentiale in treatment of fatty iver caused by diabetes mellitus. Med J Q llu. 2000; fifteen; 277- 278.

12.Trukhan DI Non-alcoholic fatty liver disease: therapeutic and dietary recommendations of the doctor of the first contact // Gastroenterology. Supplement to Consilium Medicum magazine. – 2014. – No. 2. – S. 10-15.

‘According to IMS Healthcare
for 2019 on the territory of Russia: the lowest
average price in pharmacies for 30 days of admission
in the line Essentiale ^®
Forte N is provided with the purchase of the 180 capsule format.

SARU.PCH.19.12.2692

Eliquis tablets 5 mg, 60 pcs.

The effect of other drugs on the pharmacokinetics of apixaban

Inhibitors of CYP3A4 and P-glycoprotein. The combination of apixaban with ketoconazole (at a dose of 400 mg, once a day), which is a potent inhibitor of both the CYP3A4 isoenzyme and P-glycoprotein, led to an increase in the average AUC of apixaban by 2 times and the average Cmax by 1.6 times.No dose adjustment of apixaban is required when combined with ketoconazole, but apixaban should be used with caution in patients receiving systemic therapy with azole antifungal agents, in particular ketoconazole, or other potent inhibitors of the CYP3A4 isoenzyme and P-glycoprotein.

Drugs that are not potent inhibitors of the isoenzyme CYP3A4 and P-glycoprotein (eg diltiazem, naproxen, amiodarone, verapamil, quinidine) are likely to lead to an increase in the concentration of apixaban in blood plasma to a lesser extent.For example, diltiazem (a moderate inhibitor of the CYP3A4 isoenzyme and a weak inhibitor of P-glycoprotein) at a dose of 360 mg 1 time per day led to an increase in the average AUC values ​​of apixaban by 1.4 times and the average Cmax values ​​by 1.3 times. Naproxen (an inhibitor of P-glycoprotein), when used in a dose of 500 mg in healthy volunteers, caused an increase in the average AUC and Cmax of apixaban by 1.5 and 1.6 times, respectively. At the same time, an increase in the values ​​of indicators of the blood coagulation system (PT, INR and APTT) was noted.However, there was no effect of naproxen on arachidonic acid-induced platelet aggregation, as well as a clinically significant lengthening of bleeding time.

No dose adjustment of apixaban is required when combined with moderate inhibitors of the CYP3A4 isoenzyme and / or P-glycoprotein.

Inducers of CYP3A4 isoenzyme and P-glycoprotein. The combination of apixaban with rifampicin (a potent inducer of CYP3A4 isoenzyme and P-glycoprotein) led to a decrease in the average AUC and Cmax values ​​of apixaban by approximately 54 and 42%, respectively.Apparently, the combination of apixaban with other powerful inducers of the isoenzyme CYP3A4 and P-glycoprotein (in particular phenytoin, carbamazepine, phenobarbital, or St. John’s wort preparations) may also lead to a decrease in the concentration of apixaban in the blood plasma. Correction of the dose of apixaban when combined with drugs of this group is not required, however, these funds should be combined with caution.

Anticoagulants, platelet aggregation inhibitors and NSAIDs. After the combined administration of enoxaparin (once, at a dose of 40 mg) and apixaban (once, at a dose of 5 mg), an additive effect of these drugs on FXa activity was observed.

Signs of pharmacokinetic or pharmacodynamic interaction of apixaban with acetylsalicylic acid (at a dose of 325 mg, 1 time per day) were not observed in healthy people.

The combination of apixaban with clopidogrel (at a dose of 75 mg, 1 time per day) or a combination of clopidogrel (75 mg) and acetylsalicylic acid (162 mg, 1 time per day) in the phase I clinical study did not lead to an increase in bleeding time or further depression platelet aggregation compared with the use of these antiplatelet agents in monotherapy.The increase in blood coagulation system parameters (PT, INR and APTT) was consistent with the effects of apixaban when used in monotherapy.

It is not recommended to concomitantly use drugs that may be associated with the development of serious bleeding, such as unfractionated heparin or heparin derivatives (including low molecular weight heparins), oligosaccharides that inhibit FXa (eg fondaparinux), direct thrombin II inhibitors (eg desirudin), thrombolytic Drugs, antagonists of receptors for glycoproteins IIb / IIIa, dipyridamole, dextran, sulfinpyrazone, vitamin K antagonists and other oral anticoagulants.It should be noted that unfractionated heparin can be used in doses necessary to maintain patency of the central venous or arterial catheter.

In patients after elective hip or knee arthroplasty, concomitant administration of apixaban with other antiplatelet agents or antithrombotic drugs is not recommended.

Combination with other drugs. There was no clinically significant pharmacokinetic or pharmacodynamic interaction of apixaban with atenolol or famotidine.

The combination of apixaban (at a dose of 10 mg) with atenolol (at a dose of 100 mg) did not lead to the development of clinically significant changes in the parameters of apixaban pharmacokinetics, however, it was accompanied by a decrease in the average AUC and Cmax values ​​of apixaban by 15 and 18%, respectively, compared with the monotherapy regimen. Appointment of apixaban (10 mg dose) with famotidine (40 mg dose) did not affect the AUC or Cmax values ​​of apixaban.

Effect of apixaban on the pharmacokinetics of other drugs

In in vitro studies, apixaban did not inhibit the activity of isoenzymes CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2D6 or CYP3A4 (inhibitory concentration at the same time (IC50)> 45 μmol / L) weakly suppressed the activity of the isoenzyme CYP2C19 (IC50> 20 μmol / L) at a concentration significantly exceeding the Cmax of the drug in blood plasma during its clinical use.Apixaban is not an inducer of CYP1A2, CYP2B6, CYP3A4 / 5 isoenzymes at concentrations up to 20 μmol / L. In this regard, it is expected that when used together, it will not affect the clearance of drugs metabolized by these isoenzymes. In addition, apixaban does not significantly inhibit P-glycoprotein activity. In studies in healthy volunteers, apixaban did not significantly alter the pharmacokinetics of digoxin, naproxen, or atenolol.

instructions for use (dosage, indications, composition, side effects from the drug)

Special instructions

Risk of bleeding

As with other anticoagulants, patients receiving Eliquis ^® should be closely monitored for signs of bleeding.In conditions with a high risk of bleeding, the drug is recommended to be used with caution. The use of the drug Eliquis ^® should be discontinued if severe bleeding develops.

Although therapy with apixaban does not require constant monitoring of its concentration in the blood, it may sometimes be advisable to perform a calibrated quantitative analysis of anti-Xa-factor activity in those exceptional cases where data on the effects of apixaban can guide clinical decisions, for example, in case of overdose and emergency surgery …

The use of the drug is not recommended for liver diseases accompanied by disorders in the blood coagulation system and a clinically significant risk of bleeding. It is necessary to stop using the drug if severe bleeding occurs.

In the event of a complication in the form of bleeding, drug therapy should be stopped; it is also necessary to establish the source of bleeding. Among the possible options for stopping bleeding, surgical hemostasis or transfusion of fresh frozen plasma may be considered; in life-threatening conditions that cannot be controlled using the above methods, the possibility of introducing a prothrombin complex concentrate (CPC) or recombinant blood coagulation factor VIIa can be considered.In healthy volunteers, the reversibility of the pharmacodynamic effects of Eliquis ^® according to the results of the thrombin generation test was observed after the infusion of a CPC containing 4 blood coagulation factors. However, there is no experience of clinical use of a PDA containing 4 blood coagulation factors in order to stop bleeding in patients receiving Eliquis ^® . There is currently no experience with the use of recombinant factor VIIa in patients receiving apixaban therapy.

Care should be taken with the simultaneous use of apixaban with NSAIDs (including acetylsalicylic acid) due to the fact that these drugs increase the risk of bleeding.

The simultaneous use of Eliquis ^® and acetylsalicylic acid (ASA) in elderly patients requires caution due to the potentially higher risk of bleeding. In patients with atrial fibrillation and conditions requiring mono or dual antiplatelet therapy, a careful risk and benefit assessment should be carried out before prescribing apixaban.

Interaction with other drugs affecting hemostasis

Due to the high risk of bleeding, simultaneous use with any other anticoagulants is contraindicated.

The simultaneous use of Eliquis ^® with antiplatelet agents increases the risk of bleeding.

Therapy in patients simultaneously receiving NSAIDs, including ASA, should be carried out with caution.

After surgery, it is not recommended to use other platelet aggregation inhibitors simultaneously with Eliquis ^® .

In patients with atrial fibrillation and conditions requiring antiplatelet therapy with one or two drugs, it is necessary to conduct a thorough assessment of the ratio of potential benefits and risks before starting concomitant therapy with Eliquis ^® .

In a clinical study involving patients with atrial fibrillation, the simultaneous use of ASA led to an increased risk of major bleeding both while taking apixaban and while taking warfarin.In this clinical study, combination therapy with two antiplatelet agents was rarely used.

The use of thrombolytic agents for the treatment of acute ischemic stroke

Experience with the use of thrombolytic agents for the treatment of acute ischemic stroke in patients receiving apixaban is very limited.

Patients with artificial heart valves

The safety and efficacy of the drug in patients with artificial heart valves with and without atrial fibrillation has not been studied.The use of Eliquis ^® is not recommended for this group of patients.

Surgical and invasive procedures

The use of Eliquis ^® should be discontinued at least 48 hours before a planned surgery or invasive procedure with a moderate or high risk of bleeding. This includes interventions in which the likelihood of clinically significant bleeding is not excluded or for which the risk of bleeding is unacceptable.

The use of Eliquis ^® should be discontinued at least 24 hours before a planned surgery or invasive procedure with a low risk of bleeding.This includes interventions for which minimal, non-localized, or easily controlled bleeding is expected.

If an operation or invasive procedure cannot be postponed, it should be carried out with appropriate caution, given the increased risk of bleeding. The risk of bleeding should be correlated with the need for emergency intervention. Nonvalvular atrial fibrillation usually does not require the use of “bridge therapy” for 24-48 hours after discontinuation of apixaban before surgery.

After an invasive procedure or surgery, the use of Eliquis ^® should be resumed as soon as possible, provided that the clinical situation permits and sufficient hemostasis has been established (for information on cardioversion, see the Dosage Regimen section).

Temporary cessation of therapy

Discontinuation of anticoagulants, including Eliquis ^® , due to active bleeding, elective surgery or invasive procedure increases the patient’s risk of thrombosis.Interruptions in treatment should be avoided, and if for any reason a temporary cessation of anticoagulant therapy with Eliquis ^® is required, it should be resumed as soon as possible.

Treatment of deep vein thrombosis and pulmonary embolism

It is not recommended to replace therapy with unfractionated heparin with Eliquis ^® during the initiation of therapy in patients with pulmonary embolism with unstable hemodynamics, possible thrombolysis or pulmonary artery thrombectomy, i.e.because the safety and efficacy of apixaban in these clinical situations have not been established.

Patients with cancer

The efficacy and safety of apixaban in the treatment of DVT, the treatment of PE and the prevention of recurrent DVT and PE (rVTE) in patients with actively progressive malignant neoplasm have not been established.

Patients with renal failure

Limited clinical data show that in patients with severe renal impairment (CC 15–29 ml / min), plasma apixaban concentrations increase, which may increase the risk of bleeding.For the treatment of DVT, the treatment of PE and the prevention of recurrent DVT and PE (rVTE), apixaban in patients with severe renal impairment (CC 15–29 ml / min) should be used with caution.

For the prevention of stroke and systemic embolism in patients with NFP, patients with severe renal impairment (CC 15-29 ml / min) and patients with serum creatinine levels ≥1.5 mg / dL (133 μmol / L) in combination with age ≥80 years or body weight ≤60 kg, the dose of apixaban should be reduced to 2.5 mg 2 times / day.

Due to the lack of experience in the clinical use of apixaban in patients with CC 15 ml / min or on dialysis, apixaban intake in this group of patients is not recommended.

Elderly patients

The risk of bleeding may increase with age.

Also, the simultaneous use of Eliquis ^® and ASA in elderly patients requires caution due to the potentially higher risk of bleeding.

Body weight

With a low body weight (60 kg), the risk of bleeding may increase.

Patients with hepatic impairment

Eliquis ^® is contraindicated in patients with liver disease associated with coagulopathy and a clinically significant risk of bleeding.

The drug is not recommended for patients with severe liver dysfunction.

The drug should be used with caution in patients with mild to moderate hepatic impairment (stage A or B according to Child-Pugh classification).

Patients with elevated liver enzymes ALT / AST> 2 × ULN or total bilirubin ≥ 1.5 × ULN were excluded from clinical trials. Therefore, in this population, the drug Eliquis ^® should be used with caution. Before using the drug Eliquis ^® , it is necessary to check the biochemical parameters of the liver function.

Interaction with cytochrome inhibitors P 450 and inhibitors P-gp

It is not recommended to use the drug Eliquis ^® in patients receiving concomitant systemic treatment with potent inhibitors of the isoenzyme CYP3A4 and P-glycoprotein, such as antimycotics of the azole group (for example, ketoconazole, itraconazole, voriconazole and posaconazole) and HIV protease inhibitors (for example) …These drugs can increase apixaban exposure by 2 times or more in the presence of additional factors that also increase apixaban exposure (eg, severe renal impairment).

Interaction with isoenzyme inducers CYP 3 A 4 and P-gp

The simultaneous use of Eliquis ^® with powerful inducers of the isoenzyme CYP3A4 and inducers of P-gp (for example, rifampicin, phenytoin, carbamazepine, phenobarbital and St. John’s wort preparations) can also lead to a decrease in the concentration of apixaban in blood plasma (by about 50%).In a clinical study involving patients with atrial fibrillation, a decrease in efficacy and an increased risk of bleeding were noted with the simultaneous use of apixaban and powerful inducers of the isoenzyme CYP3A4 and P-gp compared with the use of apixaban in monotherapy.

The following recommendations apply to patients receiving systemic therapy with potent inhibitors of the isoenzyme CYP3A4 and P-gp:

– in order to prevent venous thromboembolism in patients after planned hip or knee arthroplasty, to prevent stroke and systemic thromboembolism in nonvalvular atrial fibrillation, as well as to prevent recurrence of DVT and PE, apixaban should be used with caution;

– for the treatment of DVT and PE, apixaban should not be used, becausebecause efficiency may be reduced.

Surgical interventions associated with hip fracture

The efficacy and safety of apixaban in clinical studies in patients after surgery for hip fracture has not been evaluated. Therefore, it is not recommended for these patients.

Laboratory parameters

The effect of apixaban mechanism of action on blood clotting parameters (eg, prothrombin time (PT), INR, and activated partial thromboplastin time (APTT)) was as expected.The observed changes in these indicators of blood coagulation at the assumed therapeutic dose were small and had significant variability.

Information on excipients

Eliquis ^® contains lactose. Patients with rare hereditary disorders such as galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption should not take Eliquis ^® .

Performing spinal, epidural anesthesia or punctures in patients receiving Eliquis ^®

When performing spinal or epidural anesthesia or diagnostic puncture of these areas in patients receiving antithrombotic agents for the prevention of thromboembolism, there is a risk of developing epidural or spinal hematomas, which, in turn, can cause permanent or irreversible paralysis.This risk may be further increased with the use of an installed epidural catheter in the postoperative period or with the concurrent use of other drugs that affect hemostasis. Installed epidural or subarachnoid catheters should be removed at least 5 hours before the first dose of Eliquis ^® is administered. The risk may also be increased with traumatic or repeated epidural or spinal punctures. Patients should be monitored frequently for signs and symptoms of neurologic deficits (eg, numbness or weakness in the legs, bowel or bladder dysfunction).If a neurological abnormality is detected, urgent diagnosis and treatment is necessary. Prior to neuraxial intervention, the clinician should assess the potential benefit / risk ratio for patients receiving or receiving anticoagulant therapy to prevent thrombosis.

There is no clinical experience with apixaban in patients with an intrathecal or epidural catheter installed. If this situation is necessary, based on the pharmacokinetic characteristics of apixaban, an interval of 20-30 hours should be observed (i.e.i.e. 2 elimination half-lives) between the last dose of apixaban taken and catheter removal, so at least one dose of apixaban should be skipped before catheter removal. The next dose of apixaban can be used no earlier than 5 hours after the removal of the catheter. As is the case with all new anticoagulant drugs, experience with apixaban for neuraxial blockade is limited, and therefore extreme caution should be exercised in such a situation.

Influence on the ability to drive vehicles and use mechanisms

The drug Eliquis ^® does not affect or does not significantly affect the ability to drive vehicles and work with mechanisms.

Eliquis® antidote approved to reduce the risk of side effects in emergencies

Antidote approved for Eliquis ^® , which reduces the risk of side effects in emergencies

The FDA approved the first and so far the only antidote to factor Xa inhibitors – Andexa ^® (andexanet alpha) ¹ .It is a recombinant coagulation factor Xa devoid of procoagulant activity and

can rapidly block the effect of direct anticoagulants, coagulation factor Xa inhibitors such as Pfizer’s Eliquis® (apixaban).
This registration was eagerly awaited by clinicians of various specialties, since the presence of an antidote to the increasingly used modern anticoagulants will increase the safety of treatment by preventing or stopping life-threatening bleeding.

Anticoagulants related to factor Xa inhibitors block a key link in the external and internal pathways of the blood coagulation system, preventing the formation of blood clots in the venous and arterial systems.

Modern oral anticoagulants (OACs) have a better safety profile compared to traditionally used “old” anticoagulants
– vitamin K antagonists ² . Among their areas of application are the prevention of cardioembolic stroke in non-valvular atrial fibrillation, treatment of deep vein thrombosis and pulmonary embolism and further prevention of their recurrence, thromboprophylaxis in hip and knee arthroplasty.The drug Eliquis® for atrial fibrillation has the best ratio of efficacy and safety among other POACs, showing superiority in the prevention of stroke and a lower risk of major bleeding in clinical trials in comparison with warfarin ^{3 4 5 6 7 8} . Sometimes there are situations when it is necessary to quickly block the action of the drug, for example, during an emergency operation in a patient who has recently taken it, or when life-threatening bleeding develops.

“The approval of the antidote andexanet alfa is a big step forward in the treatment of patients with thromboembolic conditions and reducing the risk of complications, – noted Pfizer Medical Director Kirill Tverskoy. “Now, when every minute counts, doctors can more effectively and confidently help patients.”

About Eliquis ^® (INN apixaban)

Eliquis ^® (apixaban) is a direct oral anticoagulant inhibitor of Xa factor, has a predictable anticoagulant effect, independent of gender, age, weight of the patient, has no pronounced drug interactions, its absorption does not depend on food intake.It is excreted by the kidneys by only 27% unchanged ⁹ .
Eliquis is the only new oral anticoagulant that outperforms warfarin in three key parameters in patients with atrial fibrillation ^{2 3} :

• reduces the incidence of stroke and systemic embolism by 21%,
• reduces the risk of major bleeding by 31%,
• reduces overall mortality by 11%.

In addition, apixaban therapy significantly reduces the risk of bleeding in patients with acute venous thromboembolism with comparable efficacy
compared with standard therapy ^{10 11} .

Pfizer: Building a Healthy World Together

Through innovation and global resources, Pfizer works to improve the health and well-being of people at every stage of life. We strive to set high standards for the quality and safety of our research, development and production of medicines. The company’s product portfolio includes pharmaceuticals, including vaccines, as well as world-renowned vitamins and other health-promoting products.Every day, Pfizer employees work in developed and developing countries to improve prevention and treatment of today’s most serious diseases. In keeping with our commitment as the world’s leading biopharmaceutical company, Pfizer works with healthcare professionals, government agencies and local communities to ensure and expand the availability of reliable,
quality medical care around the world. For over 160 years, Pfizer has worked to improve the lives of those who count on us.

¹ https://globenewswire.com/news-release/2018/05/04/1496534/0/en/US-FDA-Approves-Portola-Pharmaceuticals-Andexxa-First-and-Only-Antidote-for -the-Reversal-of-Factor-Xa-Inhibitors.html
² Sulimov V.A., Napalkov D.A., Sokolova A.A. Comparative efficacy and safety of new oral anticoagulants. Rational Pharmacotherapy in Cardiology 2013; 9 (4): 433-438.
³ Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation.N Engl J Med. 2011 Sep 15; 365 (11): 981-92.
⁴ Halvorsen S, Atar D, Yang H, et al. Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial. Eur Heart J. 2014 Jul 21; 35 (28): 1864-72.
⁵ Halperin JL, Hankey GJ, Wojdyla DM, et al. Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF).Circulation. 2014 Jul 8; 130 (2): 138-46.
⁶ Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011 Sep 8; 365 (10): 883-91.
⁷ Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation.