MedPath

ELIQUIS

These highlights do not include all the information needed to use ELIQUIS safely and effectively. See full prescribing information for ELIQUIS. ELIQUIS (apixaban) tablets, for oral useInitial U.S. Approval: 2012

Approved
Approval ID

41a133ef-e461-48ad-8221-b735bdd0ec25

Product Type

HUMAN PRESCRIPTION DRUG LABEL

Effective Date

Feb 1, 2023

Manufacturers
FDA

Aphena Pharma Solutions - Tennessee, LLC

DUNS: 128385585

Products 1

Detailed information about drug products covered under this FDA approval, including NDC codes, dosage forms, ingredients, and administration routes.

apixaban

Product Details

FDA regulatory identification and product classification information

FDA Identifiers
NDC Product Code71610-662
Application NumberNDA202155
Product Classification
M
Marketing Category
C73594
G
Generic Name
apixaban
Product Specifications
Route of AdministrationORAL
Effective DateFebruary 1, 2023
FDA Product Classification

INGREDIENTS (11)

apixabanActive
Quantity: 5 mg in 1 1
Code: 3Z9Y7UWC1J
Classification: ACTIB
anhydrous lactoseInactive
Code: 3SY5LH9PMK
Classification: IACT
MICROCRYSTALLINE CELLULOSEInactive
Code: OP1R32D61U
Classification: IACT
croscarmellose sodiumInactive
Code: M28OL1HH48
Classification: IACT
sodium lauryl sulfateInactive
Code: 368GB5141J
Classification: IACT
magnesium stearateInactive
Code: 70097M6I30
Classification: IACT
lactose monohydrateInactive
Code: EWQ57Q8I5X
Classification: IACT
HYPROMELLOSE, UNSPECIFIEDInactive
Code: 3NXW29V3WO
Classification: IACT
titanium dioxideInactive
Code: 15FIX9V2JP
Classification: IACT
triacetinInactive
Code: XHX3C3X673
Classification: IACT
ferric oxide redInactive
Code: 1K09F3G675
Classification: IACT

Drug Labeling Information

Boxed Warning section

LOINC: 34066-1Updated: 2/9/2018

CONTRAINDICATIONS SECTION

LOINC: 34070-3Updated: 11/29/2017

4 CONTRAINDICATIONS

ELIQUIS is contraindicated in patients with the following conditions:

Active pathological bleeding [see Warnings and Precautions (5.2) and Adverse Reactions (6.1)]

Severe hypersensitivity reaction to ELIQUIS (e.g., anaphylactic reactions) [see Adverse Reactions (6.1)]
Key Highlight

Active pathological bleeding (4)

Severe hypersensitivity to ELIQUIS (4)

WARNINGS AND PRECAUTIONS SECTION

LOINC: 43685-7Updated: 4/20/2021

5 WARNINGS AND PRECAUTIONS

5.1 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 [see Dosage and Administration (2.4) and Clinical Studies (14.1)].

5.2 Bleeding

ELIQUIS increases the risk of bleeding and can cause serious, potentially fatal, bleeding [see Dosage and Administration (2.1) and Adverse Reactions (6.1)].

Concomitant use of drugs affecting hemostasis increases the risk of bleeding. These include aspirin and other antiplatelet agents, other anticoagulants, heparin, thrombolytic agents, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and nonsteroidal anti- inflammatory drugs (NSAIDs) [see Drug Interactions (7.3)].

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.

Reversal of Anticoagulant Effect

An agent to reverse the anti-factor Xa activity of apixaban is available. The pharmacodynamic effect of ELIQUIS can be expected to persist for at least 24 hours after the last dose, i.e., for about two drug half-lives. Prothrombin complex concentrate (PCC), activated prothrombin complex concentrate or recombinant factor VIIa may be considered, but have not been evaluated in clinical studies [see Clinical Pharmacology (12.2)]. When PCCs are used, monitoring for the anticoagulation effect of apixaban using a clotting test (PT, INR, or aPTT) or anti-factor Xa (FXa) activity is not useful and is not recommended. Activated oral charcoal reduces absorption of apixaban, thereby lowering apixaban plasma concentration [see Overdosage (10)].

Hemodialysis does not appear to have a substantial impact on apixaban exposure [see Clinical Pharmacology (12.3)]. Protamine sulfate and vitamin K are not 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 no experience with systemic hemostatics (desmopressin) in individuals receiving ELIQUIS, and they are not expected to be effective as a reversal agent.

5.3 Spinal/Epidural Anesthesia or Puncture

When neuraxial anesthesia (spinal/epidural anesthesia) or spinal/epidural puncture is employed, patients treated with antithrombotic agents for prevention of thromboembolic complications are at risk of developing 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 for signs and symptoms of neurological impairment (e.g., numbness or weakness of the legs, or bowel or bladder dysfunction). If neurological compromise is noted, urgent diagnosis and treatment is necessary. Prior to neuraxial intervention the physician should consider the potential benefit versus the risk in anticoagulated patients or in patients to be anticoagulated for thromboprophylaxis.

5.4 Patients with Prosthetic Heart Valves

The safety and efficacy of ELIQUIS have not been studied in patients with prosthetic heart valves. Therefore, use of ELIQUIS is not recommended in these patients.

5.5 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.

5.6 Increased Risk of Thrombosis in Patients with Triple Positive

Antiphospholipid Syndrome

Direct-acting oral anticoagulants (DOACs), including ELIQUIS, are not recommended for use in patients with triple-positive antiphospholipid syndrome (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.

Key Highlight

ELIQUIS can cause serious, potentially fatal, bleeding. Promptly evaluate signs and symptoms of blood loss. An agent to reverse the anti-factor Xa activity of apixaban is available. (5.2)

Prosthetic heart valves: ELIQUIS use not recommended. (5.4)

Increased Risk of Thrombosis in Patients with Triple Positive Antiphospholipid Syndrome: ELIQUIS use not recommended. (5.6)

ADVERSE REACTIONS SECTION

LOINC: 34084-4Updated: 11/26/2019

6 ADVERSE REACTIONS

The following clinically significant adverse reactions are discussed in greater detail in other sections of the prescribing information.

Increased Risk of Thrombotic Events After Premature Discontinuation [see Warnings and Precautions (5.1)]

Bleeding [see Warnings and Precautions (5.2)]

Spinal/Epidural Anesthesia or Puncture [see Warnings and Precautions (5.3)]

6.1 Clinical Trials Experience

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

Reduction of Risk of Stroke and Systemic Embolism in Patients with

Nonvalvular Atrial Fibrillation

The safety of ELIQUIS was evaluated in the ARISTOTLE and AVERROES studies [see Clinical Studies (14)], including 11,284 patients exposed to ELIQUIS 5 mg twice daily and 602 patients exposed to ELIQUIS 2.5 mg twice daily. The duration of ELIQUIS exposure was ≥12 months for 9375 patients and ≥24 months for 3369 patients in the two studies. In ARISTOTLE, the mean duration of exposure was 89 weeks (>15,000 patient-years). In AVERROES, the mean duration of exposure was approximately 59 weeks (>3000 patient-years).

The most common reason for treatment discontinuation in both studies was for bleeding-related adverse reactions; in ARISTOTLE this occurred in 1.7% and 2.5% of patients treated with ELIQUIS and warfarin, respectively, and in AVERROES, in 1.5% and 1.3% on ELIQUIS and aspirin, respectively.

Bleeding in Patients with Nonvalvular Atrial Fibrillation in ARISTOTLE

and AVERROES

Tables 1 and 2 show the number of patients experiencing major bleeding during the treatment period and the bleeding rate (percentage of subjects with at least one bleeding event per 100 patient-years) in ARISTOTLE and AVERROES.

Table 1: Bleeding Events in Patients with Nonvalvular Atrial Fibrillation in ARISTOTLE*

ELIQUIS
N=9088
n (per 100 pt-year)

Warfarin
N=9052
n (per 100 pt-year)

Hazard Ratio
(95% CI)

P-value

Major†

327 (2.13)

462 (3.09)

0.69 (0.60, 0.80)

<0.0001

Intracranial (ICH)‡

52 (0.33)

125 (0.82)

0.41 (0.30, 0.57)

Hemorrhagic stroke§

38 (0.24)

74 (0.49)

0.51 (0.34, 0.75)

Other ICH

15 (0.10)

51 (0.34)

0.29 (0.16, 0.51)

Gastrointestinal (GI)¶

128 (0.83)

141 (0.93)

0.89 (0.70, 1.14)

Fatal**

10 (0.06)

37 (0.24)

0.27 (0.13, 0.53)

Intracranial

4 (0.03)

30 (0.20)

0.13 (0.05, 0.37)

Non-intracranial

6 (0.04)

7 (0.05)

0.84 (0.28, 2.15)

* Bleeding events within each subcategory were counted once per subject, but subjects may have contributed events to multiple endpoints. Bleeding events were counted during treatment or within 2 days of stopping study treatment (on-treatment period).  

† Defined as clinically overt bleeding accompanied by one or more of the following: a decrease in hemoglobin of ≥2 g/dL, a transfusion of 2 or more units of packed red blood cells, bleeding at a critical site: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal or with fatal outcome.
‡ Intracranial bleed includes intracerebral, intraventricular, subdural, and subarachnoid bleeding. Any type of hemorrhagic stroke was adjudicated and counted as an intracranial major bleed.
§ On-treatment analysis based on the safety population, compared to ITT analysis presented in Section 14.
¶ GI bleed includes upper GI, lower GI, and rectal bleeding.
** Fatal bleeding is an adjudicated death with the primary cause of death as intracranial bleeding or non-intracranial bleeding during the on-treatment period.

In ARISTOTLE, the results for major bleeding were generally consistent across most major subgroups including age, weight, CHADS2 score (a scale from 0 to 6 used to estimate risk of stroke, with higher scores predicting greater risk), prior warfarin use, geographic region, and aspirin use at randomization (Figure 1). Subjects treated with ELIQUIS with diabetes bled more (3% per year) than did subjects without diabetes (1.9% per year).

Figure 1: Major Bleeding Hazard Ratios by Baseline Characteristics – ARISTOTLE Study

![ARISTOTLE Major Bleeding Forest Plot](/dailymed/image.cfm?name=eliquis- forest-fig1.jpg&id=691312)

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

Table 2: Bleeding Events in Patients with Nonvalvular Atrial Fibrillation in AVERROES

ELIQUIS
N=2798
n (%/year)

Aspirin
N=2780
n (%/year)

Hazard Ratio
(95% CI)

P-value

Events associated with each endpoint were counted once per subject, but subjects may have contributed events to multiple endpoints.

Major

45 (1.41)

29 (0.92)

1.54 (0.96, 2.45)

0.07

Fatal

5 (0.16)

5 (0.16)

0.99 (0.23, 4.29)

Intracranial

11 (0.34)

11 (0.35)

0.99 (0.39, 2.51)

Other Adverse Reactions

Hypersensitivity reactions (including drug hypersensitivity, such as skin rash, and anaphylactic reactions, such as allergic edema) and syncope were reported in <1% of patients receiving ELIQUIS.

Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement

Surgery

The safety of ELIQUIS has been evaluated in 1 Phase II and 3 Phase III studies including 5924 patients exposed to ELIQUIS 2.5 mg twice daily undergoing major orthopedic surgery of the lower limbs (elective hip replacement or elective knee replacement) treated for up to 38 days.

In total, 11% of the patients treated with ELIQUIS 2.5 mg twice daily experienced adverse reactions.

Bleeding results during the treatment period in the Phase III studies are shown in Table 3. Bleeding was assessed in each study beginning with the first dose of double-blind study drug.

Table 3: Bleeding During the Treatment Period in Patients Undergoing Elective Hip or Knee Replacement Surgery

Bleeding Endpoint*

ADVANCE-3
Hip Replacement Surgery

ADVANCE-2
Knee Replacement Surgery

ADVANCE-1
Knee Replacement Surgery

  • All bleeding criteria included surgical site bleeding.
    † Includes 13 subjects with major bleeding events that occurred before the first dose of ELIQUIS (administered 12 to 24 hours post-surgery).
    ‡ Includes 5 subjects with major bleeding events that occurred before the first dose of ELIQUIS (administered 12 to 24 hours post-surgery).
    § Intracranial, intraspinal, intraocular, pericardial, an operated joint requiring re-operation or intervention, intramuscular with compartment syndrome, or retroperitoneal. Bleeding into an operated joint requiring re- operation or intervention was present in all patients with this category of bleeding. Events and event rates include one enoxaparin-treated patient in ADVANCE-1 who also had intracranial hemorrhage.
    ¶ CRNM = clinically relevant nonmajor.

ELIQUIS
2.5 mg po bid
35±3 days

Enoxaparin
40 mg sc qd
35±3 days

ELIQUIS
2.5 mg po bid
12±2 days

Enoxaparin
40 mg sc qd
12±2 days

ELIQUIS
2.5 mg po bid
12±2 days

Enoxaparin
30 mg sc q12h 12±2 days

First dose
12 to 24 hours post surgery

First dose
9 to 15 hours prior to surgery

First dose
12 to 24 hours post surgery

First dose
9 to 15 hours prior to surgery

First dose
12 to 24 hours post surgery

First dose
12 to 24 hours post surgery

All treated

N=2673

N=2659

N=1501

N=1508

N=1596

N=1588

Major (including surgical site)

22 (0.82%)†

18 (0.68%)

9 (0.60%)‡

14 (0.93%)

11 (0.69%)

22 (1.39%)

Fatal

0

0

0

0

0

1 (0.06%)

Hgb decrease ≥2 g/dL

13 (0.49%)

10 (0.38%)

8 (0.53%)

9 (0.60%)

10 (0.63%)

16 (1.01%)

Transfusion of ≥2 units RBC

16 (0.60%)

14 (0.53%)

5 (0.33%)

9 (0.60%)

9 (0.56%)

18 (1.13%)

Bleed at critical site§

1 (0.04%)

1 (0.04%)

1 (0.07%)

2 (0.13%)

1 (0.06%)

4 (0.25%)

Major
+ CRNM¶

129 (4.83%)

134 (5.04%)

53 (3.53%)

72 (4.77%)

46 (2.88%)

68 (4.28%)

All

313 (11.71%)

334 (12.56%)

104 (6.93%)

126 (8.36%)

85 (5.33%)

108 (6.80%)

Adverse reactions occurring in ≥1% of patients undergoing hip or knee replacement surgery in the 1 Phase II study and the 3 Phase III studies are listed in Table 4.

Table 4: Adverse Reactions Occurring in ≥1% of Patients in Either Group Undergoing Hip or Knee Replacement Surgery

ELIQUIS, n (%)
2.5 mg po bid


N=5924

Enoxaparin, n (%)
40 mg sc qd or
30 mg sc q12h
N=5904

Nausea

153 (2.6)

159 (2.7)

Anemia (including postoperative and hemorrhagic anemia, and respective laboratory parameters)

153 (2.6)

178 (3.0)

Contusion

83 (1.4)

115 (1.9)

Hemorrhage (including hematoma, and vaginal and urethral hemorrhage)

67 (1.1)

81 (1.4)

Postprocedural hemorrhage (including postprocedural hematoma, wound hemorrhage, vessel puncture-site hematoma, and catheter-site hemorrhage)

54 (0.9)

60 (1.0)

Transaminases increased (including alanine aminotransferase increased and alanine aminotransferase abnormal)

50 (0.8)

71 (1.2)

Aspartate aminotransferase increased

47 (0.8)

69 (1.2)

Gamma-glutamyltransferase increased

38 (0.6)

65 (1.1)

Less common adverse reactions in ELIQUIS-treated patients undergoing hip or knee replacement surgery occurring at a frequency of ≥0.1% to <1%:

Blood and lymphatic system disorders: thrombocytopenia (including platelet count decreases)

Vascular disorders: hypotension (including procedural hypotension)

Respiratory, thoracic, and mediastinal disorders: epistaxis

Gastrointestinal disorders: gastrointestinal hemorrhage (including hematemesis and melena), hematochezia

Hepatobiliary disorders: liver function test abnormal, blood alkaline phosphatase increased, blood bilirubin increased

Renal and urinary disorders: hematuria (including respective laboratory parameters)

Injury, poisoning, and procedural complications: wound secretion, incision- site hemorrhage (including incision-site hematoma), operative hemorrhage

Less common adverse reactions in ELIQUIS-treated patients undergoing hip or knee replacement surgery occurring at a frequency of <0.1%:

Gingival bleeding, hemoptysis, hypersensitivity, muscle hemorrhage, ocular hemorrhage (including conjunctival hemorrhage), rectal hemorrhage

Treatment of DVT and PE and Reduction in the Risk of Recurrence of DVT or

PE

The safety of ELIQUIS has been evaluated in the AMPLIFY and AMPLIFY-EXT studies, including 2676 patients exposed to ELIQUIS 10 mg twice daily, 3359 patients exposed to ELIQUIS 5 mg twice daily, and 840 patients exposed to ELIQUIS 2.5 mg twice daily.

Common adverse reactions (≥1%) were gingival bleeding, epistaxis, contusion, hematuria, rectal hemorrhage, hematoma, menorrhagia, and hemoptysis.

AMPLIFY Study

The mean duration of exposure to ELIQUIS was 154 days and to enoxaparin/warfarin was 152 days in the AMPLIFY study. Adverse reactions related to bleeding occurred in 417 (15.6%) ELIQUIS-treated patients compared to 661 (24.6%) enoxaparin/warfarin-treated patients. The discontinuation rate due to bleeding events was 0.7% in the ELIQUIS-treated patients compared to 1.7% in enoxaparin/warfarin-treated patients in the AMPLIFY study.

In the AMPLIFY study, ELIQUIS was statistically superior to enoxaparin/warfarin in the primary safety endpoint of major bleeding (relative risk 0.31, 95% CI [0.17, 0.55], P-value <0.0001).

Bleeding results from the AMPLIFY study are summarized in Table 5.

Table 5: Bleeding Results in the AMPLIFY Study

ELIQUIS
N=2676
n (%)

Enoxaparin/Warfarin
N=2689
n (%)

Relative Risk (95% CI)

  • CRNM = clinically relevant nonmajor bleeding.
    Events associated with each endpoint were counted once per subject, but subjects may have contributed events to multiple endpoints.

Major

15 (0.6)

49 (1.8)

0.31 (0.17, 0.55)
p<0.0001

CRNM*

103 (3.9)

215 (8.0)

Major + CRNM

115 (4.3)

261 (9.7)

Minor

313 (11.7)

505 (18.8)

All

402 (15.0)

676 (25.1)

Adverse reactions occurring in ≥1% of patients in the AMPLIFY study are listed in Table 6.

Table 6: Adverse Reactions Occurring in ≥1% of Patients Treated for DVT and PE in the AMPLIFY Study

ELIQUIS
N=2676
n (%)

Enoxaparin/Warfarin
N=2689
n (%)

Epistaxis

77 (2.9)

146 (5.4)

Contusion

49 (1.8)

97 (3.6)

Hematuria

46 (1.7)

102 (3.8)

Menorrhagia

38 (1.4)

30 (1.1)

Hematoma

35 (1.3)

76 (2.8)

Hemoptysis

32 (1.2)

31 (1.2)

Rectal hemorrhage

26 (1.0)

39 (1.5)

Gingival bleeding

26 (1.0)

50 (1.9)

AMPLIFY-EXT Study

The mean duration of exposure to ELIQUIS was approximately 330 days and to placebo was 312 days in the AMPLIFY-EXT study. Adverse reactions related to bleeding occurred in 219 (13.3%) ELIQUIS-treated patients compared to 72 (8.7%) placebo-treated patients. The discontinuation rate due to bleeding events was approximately 1% in the ELIQUIS-treated patients compared to 0.4% in those patients in the placebo group in the AMPLIFY-EXT study.

Bleeding results from the AMPLIFY-EXT study are summarized in Table 7.

Table 7: Bleeding Results in the AMPLIFY-EXT Study

ELIQUIS 2.5 mg bid
N=840
n (%)

ELIQUIS 5 mg bid
N=811
n (%)

Placebo
N=826
n (%)

  • CRNM = clinically relevant nonmajor bleeding.
    Events associated with each endpoint were counted once per subject, but subjects may have contributed events to multiple endpoints.

Major

2 (0.2)

1 (0.1)

4 (0.5)

CRNM*

25 (3.0)

34 (4.2)

19 (2.3)

Major + CRNM

27 (3.2)

35 (4.3)

22 (2.7)

Minor

75 (8.9)

98 (12.1)

58 (7.0)

All

94 (11.2)

121 (14.9)

74 (9.0)

Adverse reactions occurring in ≥1% of patients in the AMPLIFY-EXT study are listed in Table 8.

Table 8: Adverse Reactions Occurring in ≥1% of Patients Undergoing Extended Treatment for DVT and PE in the AMPLIFY-EXT Study

ELIQUIS 2.5 mg bid
N=840
n (%)

ELIQUIS 5 mg bid
N=811
n (%)

Placebo
N=826
n (%)

Epistaxis

13 (1.5)

29 (3.6)

9 (1.1)

Hematuria

12 (1.4)

17 (2.1)

9 (1.1)

Hematoma

13 (1.5)

16 (2.0)

10 (1.2)

Contusion

18 (2.1)

18 (2.2)

18 (2.2)

Gingival bleeding

12 (1.4)

9 (1.1)

3 (0.4)

Other Adverse Reactions

Less common adverse reactions in ELIQUIS-treated patients in the AMPLIFY or AMPLIFY-EXT studies occurring at a frequency of ≥0.1% to <1%:

Blood and lymphatic system disorders: hemorrhagic anemia

Gastrointestinal disorders: hematochezia, hemorrhoidal hemorrhage, gastrointestinal hemorrhage, hematemesis, melena, anal hemorrhage

Injury, poisoning, and procedural complications: wound hemorrhage, postprocedural hemorrhage, traumatic hematoma, periorbital hematoma

Musculoskeletal and connective tissue disorders: muscle hemorrhage

Reproductive system and breast disorders: vaginal hemorrhage, metrorrhagia, menometrorrhagia, genital hemorrhage

Vascular disorders: hemorrhage

Skin and subcutaneous tissue disorders: ecchymosis, skin hemorrhage, petechiae

Eye disorders: conjunctival hemorrhage, retinal hemorrhage, eye hemorrhage

Investigations: blood urine present, occult blood positive, occult blood, red blood cells urine positive

General disorders and administration-site conditions: injection-site hematoma, vessel puncture-site hematoma

Key Highlight

Most common adverse reactions (>1%) are related to bleeding. (6.1)


To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 orwww.fda.gov/medwatch.

DOSAGE & ADMINISTRATION SECTION

LOINC: 34068-7Updated: 11/26/2019

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dose

Reduction of Risk of Stroke and Systemic Embolism in Patients with

Nonvalvular Atrial Fibrillation

The recommended dose of ELIQUIS for most patients is 5 mg taken orally twice daily.

The recommended dose of ELIQUIS is 2.5 mg twice daily in patients with at least two of the following characteristics:

age greater than or equal to 80 years

body weight less than or equal to 60 kg

serum creatinine greater than or equal to 1.5 mg/dL

Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement

Surgery

The recommended dose of ELIQUIS is 2.5 mg taken orally twice daily. The initial dose should be taken 12 to 24 hours after surgery.

In patients undergoing hip replacement surgery, the recommended duration of treatment is 35 days.

In patients undergoing knee replacement surgery, the recommended duration of treatment is 12 days.

Treatment of DVT and PE

The recommended dose of ELIQUIS is 10 mg taken orally twice daily for the first 7 days of therapy. After 7 days, the recommended dose is 5 mg taken orally twice daily.

Reduction in the Risk of Recurrence of DVT and PE

The recommended dose of ELIQUIS is 2.5 mg taken orally twice daily after at least 6 months of treatment for DVT or PE [see Clinical Studies (14.3)].

2.2 Missed Dose

If a dose of ELIQUIS is 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. The dose should not be doubled to make up for a missed dose.

2.3 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 [see Warnings and Precautions (5.2)]. ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be non- critical in location and easily controlled. 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.

2.4 Converting from or to ELIQUIS

Switching from warfarin to ELIQUIS: Warfarin should be discontinued and ELIQUIS started when the international normalized ratio (INR) is below 2.0.

Switching from ELIQUIS to warfarin: ELIQUIS affects INR, so that initial INR measurements during the transition to warfarin may not be useful for determining the appropriate dose of warfarin. One approach is to discontinue ELIQUIS and begin both a parenteral anticoagulant and warfarin at the time the next dose of ELIQUIS would have been taken, discontinuing the parenteral anticoagulant when INR reaches an acceptable range.

Switching from ELIQUIS to anticoagulants other than warfarin (oral or parenteral): Discontinue ELIQUIS and begin taking the new anticoagulant other than warfarin at the usual time of the next dose of ELIQUIS.

Switching from anticoagulants other than warfarin (oral or parenteral) to ELIQUIS: Discontinue the anticoagulant other than warfarin and begin taking ELIQUIS at the usual time of the next dose of the anticoagulant other than warfarin.

2.5 Combined P-gp and Strong CYP3A4 Inhibitors

For patients receiving ELIQUIS doses of 5 mg or 10 mg twice daily, reduce the dose by 50% when ELIQUIS is coadministered with drugs that are combined P-glycoprotein (P-gp) and strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ketoconazole, itraconazole, ritonavir) [see Clinical Pharmacology (12.3)].

In patients already taking 2.5 mg twice daily, avoid coadministration of ELIQUIS with combined P-gp and strong CYP3A4 inhibitors [see Drug Interactions (7.1)].

2.6 Administration Options

For patients who are unable to swallow whole tablets, 5 mg and 2.5 mg ELIQUIS tablets may be crushed and suspended in water, 5% dextrose in water (D5W), or apple juice, or mixed with applesauce and promptly administered orally [see Clinical Pharmacology (12.3)]. Alternatively, ELIQUIS tablets may be crushed and suspended in 60 mL of water or D5W and promptly delivered through a nasogastric tube [see Clinical Pharmacology (12.3)].

Crushed ELIQUIS tablets are stable in water, D5W, apple juice, and applesauce for up to 4 hours.

Key Highlight

Reduction of risk of stroke and systemic embolism in nonvalvular atrial fibrillation:

The recommended dose is 5 mg orally twice daily. (2.1)

In patients with at least 2 of the following characteristics: age greater than or equal to 80 years, body weight less than or equal to 60 kg, or serum creatinine greater than or equal to 1.5 mg/dL, the recommended dose is 2.5 mg orally twice daily. (2.1)

Prophylaxis of DVT following hip or knee replacement surgery:

The recommended dose is 2.5 mg orally twice daily. (2.1)

Treatment of DVT and PE:

The recommended dose is 10 mg taken orally twice daily for 7 days, followed by 5 mg taken orally twice daily. (2.1)

Reduction in the risk of recurrent DVT and PE following initial therapy:

The recommended dose is 2.5 mg taken orally twice daily. (2.1)

DOSAGE FORMS & STRENGTHS SECTION

LOINC: 43678-2Updated: 4/24/2017

3 DOSAGE FORMS AND STRENGTHS

2.5 mg, yellow, round, biconvex, film-coated tablets with “893” debossed on one side and “2½” on the other side.

5 mg, pink, oval-shaped, biconvex, film-coated tablets with “894” debossed on one side and “5” on the other side.
Key Highlight

Tablets: 2.5 mg and 5 mg (3)

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ELIQUIS - FDA Drug Approval Details