"The U.S. Food and Drug Administration today approved Kcentra (Prothrombin Complex Concentrate, Human) for the urgent reversal of vitamin K antagonist (VKA) anticoagulation in adults with acute major bleeding. Plasma is the only other product appr"...
- Clinician Information:
Eliquis Side Effects Center
Reviewed by Melissa Conrad Stöppler, MD
Eliquis (apixaban) is a blood thinner medicine that reduces blood clotting and reduces the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Eliquis belongs to a class of medicines called anticoagulant medications. CYP3A4 inhibitor drugs such as Serzone, Sporanox, Nizoral, Vfend, Reyataz, Biaxan and Ketek should not be taken while a patient is taking Eliquis. Patients may have a higher risk of bleeding if Eliquis is taken alongside other medicines that increase the risk of bleeding, such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin (Coumadin), heparin, selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs), and other medicines to help prevent or treat blood clots. The most common side effects seen with the use of Eliquis are related to bleeding.
The recommended dose of Eliquis is 5 mg taken orally, twice daily. The dosage may be adjusted based on the weight of the patient. There are no adequate and well-controlled studies of Eliquis in pregnant women. Treatment is likely to increase the risk of hemorrhage during pregnancy and delivery. Eliquis should be used during pregnancy only if the potential benefit outweighs the potential risk to the mother and fetus. Women should be instructed either to discontinue breastfeeding or to discontinue Eliquis therapy, taking into account the importance of the drug to the mother.
Our Eliquis (apixaban) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What is Prescribing information?
The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.
Eliquis FDA Prescribing Information: Side Effects
The most serious adverse reactions reported with ELIQUIS were related to bleeding [see WARNINGS AND PRECAUTIONS].
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.
The safety of ELIQUIS was evaluated in the ARISTOTLE and AVERROES studies [see Clinical Studies], 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 year) in ARISTOTLE and AVERROES.
Major bleeding was defined as clinically overt bleeding that was accompanied by one or more of the following: a decrease in hemoglobin of 2 g/dL or more; a transfusion of 2 or more units of packed red blood cells; bleeding that occurred in at least one of the following critical sites: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal; or bleeding that was fatal. Intracranial hemorrhage included intracerebral (hemorrhagic stroke), subarachnoid, and subdural bleeds.
Table 1: Bleeding Events in
Patients with Nonvalvular Atrial Fibrillation in ARISTOTLE
|Hazard Ratio (95% CI*)||P-value|
|Major†||327 (2.13)||462 (3.09)||0.69
|Gastrointestinal (GI)‡||128 (0.83)||141 (0.93)||0.89
|Intracranial||52 (0.33)||125 (0.82)||0.41
|Intraocular§||32 (0.21)||22 (0.14)||1.42
|Fatal¶||10 (0.06)||37 (0.24)||0.27
|CRNM **||318 (2.08)||444 (3.00)||0.70
|* Confidence interval.
† International Society on Thrombosis and Hemostasis (ISTH) major bleed assessed by sequential testing strategy for superiority designed to control the overall type I error in the trial.
‡ GI bleed includes upper GI, lower GI, and rectal bleeding.
§ Intraocular bleed is within the corpus of the eye (a conjunctival bleed is not an intraocular bleed).
¶Fatal bleed is an adjudicated death because of bleeding during the treatment period and includes both fatal extracranial bleeds and fatal hemorrhagic stroke.
**CRNM = clinically relevant nonmajor bleeding.
Events associated with each endpoint were counted once per subject, but subjects may have contributed events to multiple endpoints.
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, ELIQUIS dose, type of atrial fibrillation (AF), and aspirin use at randomization (Figure 1). Subjects treated with apixaban with diabetes bled more (3.0% per year) than did subjects without diabetes (1.9% per year).
Figure 1: Major Bleeding Hazard Ratios by Baseline
Characteristics - ARISTOTLE Study
Table 2: Bleeding Events in Patients with Nonvalvular
Atrial Fibrillation in AVERROES
|Hazard Ratio (95% CI)||P-value|
|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)||-|
|Events associated with each endpoint were counted once per subject, but subjects may have contributed events to multiple endpoints.|
Other Adverse Reactions
Read the entire FDA prescribing information for Eliquis (Apixaban Tablets) »
Additional Eliquis Information
Report Problems to the Food and Drug Administration
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