ELIQUIS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ELIQUIS (ELIQUIS).
Apixaban is a selective, reversible direct inhibitor of factor Xa (FXa). It inhibits both free and clot-bound FXa, thereby reducing thrombin generation and thrombus formation.
| Metabolism | Apixaban is metabolized primarily via CYP3A4/5 and to a lesser extent by CYP1A2, CYP2C8, CYP2C9, CYP2C19, and CYP2J2. It is also a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). |
| Excretion | Approximately 27% of the dose is excreted renally as unchanged drug; 25% is excreted as metabolites via the biliary/fecal route (total fecal excretion ~50% of absorbed dose). Renal clearance accounts for ~27% of total clearance; also a substrate for P-glycoprotein (P-gp). |
| Half-life | Terminal elimination half-life is 12 hours (range 9–14 hours) after multiple oral doses; supports twice-daily dosing. In elderly patients, half-life may extend by ~30%. |
| Protein binding | Approximately 87% bound to plasma proteins (albumin). |
| Volume of Distribution | Steady-state volume of distribution (Vss) is approximately 21 L (0.3 L/kg for a 70 kg individual), indicating limited tissue distribution primarily in extracellular fluid. |
| Bioavailability | Oral bioavailability is approximately 50% (range 45–58%) for the 5 mg tablet; not administered parenterally in clinical use. |
| Onset of Action | Peak plasma concentrations (Cmax) occur 3–4 hours after oral administration; anticoagulant effect (anti-Factor Xa activity) correlates with plasma concentration, with near-maximal effect at 3–4 hours. |
| Duration of Action | Anticoagulant effect persists for 12–24 hours after oral dose, corresponding to the dosing interval of 12 hours. Clinically, the effect is maintained with steady state achieved within 2–3 days. |
| Action Class | Oral Factor Xa Inhibitors |
5 mg orally twice daily for most indications; 2.5 mg orally twice daily for patients with at least two of the following characteristics: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL.
| Dosage form | SUSPENSION |
| Renal impairment | For patients with CrCl 15-29 mL/min: 2.5 mg orally twice daily; avoid use if CrCl <15 mL/min or on dialysis. |
| Liver impairment | Avoid use in patients with severe hepatic impairment (Child-Pugh C). Not recommended in patients with moderate hepatic impairment (Child-Pugh B) unless no alternative. |
| Pediatric use | Not approved for pediatric use; no FDA-approved pediatric dosing. |
| Geriatric use | Age alone does not require dose adjustment, but consider concomitant factors (e.g., low body weight, renal function); use 2.5 mg twice daily if ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ELIQUIS (ELIQUIS).
| Breastfeeding | Apixaban is excreted in human milk. The M/P ratio is unknown. Due to potential risk of bleeding in the nursing infant, breastfeeding is not recommended during apixaban therapy. |
| Teratogenic Risk | Apixaban is contraindicated in pregnancy due to the risk of hemorrhage and potential teratogenicity. Use in the first trimester may be associated with spontaneous abortion; second and third trimester use increases fetal and maternal hemorrhage risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
Premature discontinuation of apixaban increases the risk of thrombotic events. Epidural or spinal hematomas may occur in patients receiving anticoagulants and undergoing neuraxial anesthesia or spinal puncture, which can result in long-term or permanent paralysis.
| Serious Effects |
["Active pathological bleeding","History of hypersensitivity to apixaban or any component of the formulation","Severe hypersensitivity reaction (e.g., anaphylaxis) to apixaban","Concomitant use with other anticoagulants (e.g., unfractionated heparin, low molecular weight heparins, heparin derivatives, direct thrombin inhibitors, warfarin) unless transitioning therapy or for specific indications per guidelines"]
| Precautions | ["Increased risk of hemorrhagic events including intracranial, gastrointestinal, and retroperitoneal bleeding","Discontinuation for active pathological bleeding","Patients with prosthetic heart valves should not use apixaban","Dose reduction recommended in patients with severe renal impairment (CrCl 15-29 mL/min) or those receiving dual strong CYP3A4 and P-gp inhibitors","Not recommended in patients with moderate or severe hepatic impairment","Increased thromboembolic risk if apixaban is discontinued prematurely without adequate alternative anticoagulation"] |
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| Monitor for signs of bleeding in both mother and fetus. Perform periodic complete blood counts (CBC), coagulation parameters (if indicated), and assess for unexplained decreases in hemoglobin or hematocrit. Consider fetal ultrasound if hemorrhage suspected. |
| Fertility Effects | Apixaban has no known direct effect on fertility. However, anticoagulation may impair implantation or increase risk of early pregnancy loss due to bleeding at the implantation site. |