Apixaban

Apixaban is an anticoagulant (blood thinner) that reduces blood clotting and reduces the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

Apixaban is available under the following different brand names: Eliquis.

Dosage Forms and Strengths

Tablets

• 2.5 mg
• 5 mg

Dosage Considerations – Should be Given as Follows:

Stroke Prophylaxis with Atrial Fibrillation

• Indicated to reduce risk of stroke and systemic embolism associated with nonvalvular atrial fibrillation
• 5 mg orally twice daily

Postoperative Prophylaxis of DVT/PE

• Indicated following hip or knee replacement surgery
• Initial: Give 2.5 mg orally 12-24 hours after surgery
• Duration of therapy (hip replacement): 2.5 mg orally twice daily for 35 days
• Duration of therapy (knee replacement): 2.5 mg orally twice daily for 12 days
• Renal impairment, including with end-stage renal disease (ESRD) on dialysis:
  • Deep Vein Thrombosis: No dose adjustment recommended; clinical efficacy and safety studies did not enroll patients with ESRD on dialysis or patients with a CrCl less than 15 mL/min; dosing recommendations are based on pharmacokinetic and pharmacodynamic (anti-FXa activity) data in study subjects with ESRD maintained on dialysis

DVT or PE Treatment

• Indicated for treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE)
• 10 mg orally twice daily for 7 days, then 5 mg twice daily
• Reduce risk for recurrent DVT or PE
  • Indicated to reduce the risk of recurrent DVT and PE following initial 6 months treatment for DVT and/or PE
  • 2.5 mg orally twice daily
  • Renal impairment, including with end-stage renal disease (ESRD):
  • No dose adjustment recommended; clinical efficacy and safety studies did not enroll patients with ESRD on dialysis or patients with a CrCl less than 15 mL/min; dosing recommendations are based on pharmacokinetic and pharmacodynamic (anti-FXa activity) data in study subjects with ESRD maintained on dialysis

Dosage Modifications

Co-administration with dual inhibitors of CYP3A4 and P-gp

• If taking greater than 2.5 orally twice daily, decrease dose by 50%
• If taking 2.5 mg twice daily, avoid co-administration with strong dual inhibitors

Non-valvular atrial fibrillation

• Decrease dose to 2.5 mg orally twice daily in patients with any 2 of the following characteristics:
• Age 80 years or more
• Weight up to 60 kg
• Serum creatinine 1.5 mg/dL or greater

Renal impairment (nonvalvular atrial fibrillation)

• Mild-to-moderate: No dosage adjustment required
• Serum creatinine 1.5 mg/dL or greater: Decrease dose to 2.5 mg twice daily if patient has 1 additional characteristic of age80 years or more or weight up to 60 kg
• ESRD maintained on hemodialysis: 5 mg twice daily; decrease dose to 2.5 mg twice daily if 1 additional characteristic of age 80 years or more or weight up to 60 kg is present

Hepatic impairment

• Mild: No dosage adjustment required
• Moderate: Patients may have intrinsic coagulation abnormalities; data are limited and no recommendations are available
• Severe: Not recommended

Dosing Considerations

• Switching between apixaban and anticoagulants other than warfarin: Discontinue one being taken, and begin the other at the next scheduled dose
• Switching from warfarin to apixaban: Discontinue warfarin and initiate apixaban when INR less than 2.0
• Switching from apixaban to warfarin
  • Apixaban affects INR, so measurements during co-administration with warfarin may not determine appropriate warfarin dose
  • If continuous anticoagulation is necessary, discontinue apixaban and begin both a parenteral anticoagulant and warfarin at the time the next dose of apixaban would have been taken
  • Discontinue parenteral anticoagulant when INR reaches an acceptable level

Surgery/procedures

• Discontinue at least 48 hours before elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding
• Discontinue at least 24 hours before elective surgery or invasive procedures with a low risk of unacceptable or where the bleeding would be noncritical in location and easily controlled

Pediatric: Safety and efficacy not established

Administration

• May take with or without food
• Missed dose: If not taken at the scheduled time, the dose should be taken as soon as possible on the same day and twice daily administration should be resumed; do not double the dose to make up for a missed dose
• For patients who are unable to swallow whole tablets, 5 mg and 2.5 mg tablets may be crushed and suspended in water, 5% dextrose in water (D5W), or apple juice, or mixed with applesauce and promptly administered orally; alternatively, tablets may be crushed and suspended in 60 mL of water or D5W and promptly delivered through a nasogastric tube; crushed tablets are stable in water, D5W, apple juice, and applesauce for up to 4 hours

Bleeding (Aristotle Study)

• Major (2.13%, warfarin 3.09%; P <0.0001)
• Gastrointestinal (GI) (0.83%, warfarin 0.93%)
• Intracranial (0.33%, warfarin 0.82%)
• Intraocular (0.06%, warfarin 0.14%)
• Fatal (0.06%, warfarin 0.24%)
• Clinically relevant non-major bleeding (2.08%, warfarin 3.0%; P <0.0001)

Bleeding (Averroes Study)

• Major (1.41%, aspirin 0.92%; P = 0.07)
• Fatal (0.16%, aspirin 0.16%)
• Intracranial (0.34%, aspirin 0.35%)

Less common side effects of apixaban include:

• Hypersensitivity reactions (including skin rash and allergic reactions including anaphylactic reactions such as allergic swelling)
• Fainting
• Nausea
• Anemia

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

Severe Interactions of apixaban include:

• carbamazepine
• defibrotide
• dexamethasone
• fosphenytoin
• phenytoin
• prothrombin complex concentrate, human
• rifabutin
• rifampin
• St. John's wort
• warfarin

Apixaban has serious interactions with at least 64 different drugs.

Moderate Interactions of apixaban include:

• aspirin
• crofelemer
• dabrafenib
• daclatasvir
• diltiazem
• dronedarone
• efavirenz
• eliglustat
• iloperidone
• imatinib
• melatonin
• mitotane
• nintedanib
• ombitasvir/paritaprevir/ritonavir
• saw palmetto
• verapamil
• vortioxetine

Mild Interactions of apixaban include:

• None

This information does not contain all possible interactions or adverse effects. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns or for more information about this medicine.

Warnings

Discontinuing in patients with nonvalvular atrial fibrillation:

• Premature discontinuation of any oral anticoagulant, including, apixaban, increases risk of thrombotic events; consider using another anticoagulant if anticoagulation with apixaban is discontinued for a reason other than pathological bleeding or completion of a course of therapy
• An increased rate of stroke was observed following discontinuation of apixaban in clinical trials in patients with nonvalvular atrial fibrillation
• If anticoagulation with apixaban must be discontinued for a reason other than pathological bleeding, coverage with another anticoagulant should be strongly considered

Spinal/epidural hematoma:

• Increased risk of epidural or spinal hematoma when used with neuraxial anesthesia (epidural/spinal anesthesia) or spinal puncture (can result in long-term or permanent paralysis)
• Risk increased with indwelling epidural catheters for administration of analgesia or by the concomitant use of drugs affecting hemostasis (e.g., nonsteroidal anti-inflammatory drugs [NSAIDs], platelet aggregation inhibitors, other anticoagulants)
• Risk also increased by traumatic or repeated epidural or spinal puncture; if this occurs, delay apixaban administration for 48 hours
• Monitor patients for signs and symptoms of neurologic impairment; if neurologic compromise is noted, urgent treatment is necessary
• Indwelling epidural or intrathecal catheters should not be removed earlier than 24 hours after the last administration of apixaban; the next apixaban dose should not be administered earlier than 5 hours after the removal of the catheter
• Consider the potential benefit versus risk before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis

This medication contains apixaban. Do not take Eliquis if you are allergic to apixaban or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• Severe hypersensitivity (i.e., anaphylactic reactions)
• Active pathological bleeding

Effects of Drug Abuse

• None

Short-Term Effects

• See "What Are Side Effects Associated with Using Apixaban?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Apixaban?"

Cautions

• Discontinuing apixaban in the absence of adequate alternative anticoagulation increases the risk of thrombotic events
• Risk of epidural or spinal hematoma when used with neuraxial anesthesia
• Safety and efficacy has not been studied in patients with prosthetic heart valves; therefore, use of is not recommended in these patients
• Not recommended as an alternative to unfractionated heparin for the initial treatment of PE in patients who present with hemodynamic instability or who may receive thrombolysis or pulmonary embolectomy
• Co-administration with strong dual inhibitors of CYP3A4 and P-gp
• Avoid co-administration with strong dual inducers of CYP3A4 and P-gp; such drugs decrease apixaban's systemic exposure
• Increases the risk of bleeding and can cause serious, potentially fatal, bleeding
• Co-administration with other drugs that affect hemostasis increases bleeding risk (e.g., aspirin and other antiplatelet agents, other anticoagulants, heparin, thrombolytic agents, SSRIs, SNRIs, NSAIDs)
• Prolongs PT and aPTT; however, changes are small and highly variable and are not useful for monitoring anticoagulation effect of apixaban
• Reversing apixaban effect:
• No specific antidote is available to reverse anticoagulant effect, which is expected to persist for about 24 hours after the last dose (~2 half-lives)
• Because of high plasma protein binding, apixaban is not expected to be dialyzable
• Protamine sulfate and vitamin K would not be expected to affect the anticoagulant activity of apixaban
• There is no experience with antifibrinolytic agents (tranexamic acid, aminocaproic acid) in individuals receiving apixaban
• There is neither scientific rationale for reversal nor experience with systemic hemostatics (desmopressin and aprotinin) in individuals receiving apixaban
• Use of procoagulant reversal agents (e.g., prothrombin complex concentrate, activated prothrombin complex concentrate, or recombinant factor VIIa) may be considered but has not been evaluated in clinical studies
• Activated oral charcoal reduces absorption of apixaban, thereby lowering plasma concentration

Pregnancy and Lactation

• Apixaban may be acceptable for use during pregnancy. Either animal studies show no risk but human studies are not available or animal studies showed minor risks and human studies were done and showed no risk
• There is an increased incidence of maternal bleeding, primarily during gestation when studied in rats
• It is unknown whether apixaban is distributed in human breast milk; rats excreted apixaban in milk (12% of the maternal dose)
• Women should be instructed either to discontinue breastfeeding or to discontinue apixaban therapy, taking into account the importance of the drug to the mother