APIXABAN
Clinical safety rating: caution
Animal studies have proved adverse effects but may be safe for humans
Direct, selective, reversible inhibitor of factor Xa, thereby inhibiting thrombin formation and thrombus development.
| Metabolism | Metabolized primarily by CYP3A4 and CYP3A5, with minor contributions from CYP1A2, CYP2C8, CYP2C9, CYP2C19, and CYP2J2; also subject to hydrolysis and O-demethylation. |
| Excretion | Renal 27% unchanged; fecal/biliary 70% (mostly as unchanged drug via P-glycoprotein/BCRP-mediated secretion); renal clearance accounts for ~25% of total clearance |
| Half-life | 12 hours (range 10–14 h) in healthy subjects; prolonged to 18–24 h in severe renal impairment (CrCl <15 mL/min); half-life supports twice-daily dosing |
| Protein binding | 87% bound to plasma proteins (primarily albumin) |
| Volume of Distribution | 21 L (0.3 L/kg for a 70 kg person); small Vd indicates limited tissue distribution, primarily confined to plasma and extracellular fluid |
| Bioavailability | 50% oral bioavailability (dose-dependent, saturable absorption with high doses); absolute bioavailability at 10 mg is 50%; no injectable formulation available |
| Onset of Action | Oral: 1–3 hours to peak plasma concentration; onset of anticoagulation occurs within 1–2 hours based on anti-Factor Xa activity; immediate anticoagulation effect begins after first dose |
| Duration of Action | Approximately 12 hours (therapeutic effect persists throughout dosing interval); given twice daily, steady state achieved within 3 days; effect diminishes 24 hours after last dose; clinically significant anticoagulation lasts at least 12 hours |
5 mg orally twice daily for most indications; 2.5 mg orally twice daily for patients with at least two of the following: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL.
| Dosage form | TABLET |
| Renal impairment | In patients with severe renal impairment (CrCl 15-29 mL/min): 2.5 mg orally twice daily. Avoid use if CrCl <15 mL/min or on dialysis. |
| Liver impairment | Contraindicated in patients with Child-Pugh class B or C hepatic impairment. Use with caution in mild hepatic impairment (Child-Pugh class A) with no dose adjustment required. |
| Pediatric use | For patients <18 years: safety and efficacy not established. In select pediatric dosing for venous thromboembolism: 10 mg orally twice daily for 7 days then 2.5 mg twice daily for body weight ≥50 kg; weight-based adjustments for lower weights (e.g., 2.5 mg twice daily for 10-20 kg) per clinical studies. |
| Geriatric use | No specific dose adjustment solely for age. Apply renal and body weight criteria; patients ≥80 years are included in the 2.5 mg twice daily dosing criteria (if at least two of: age ≥80, weight ≤60 kg, Cr ≥1.5 mg/dL). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong dual inducers of CYP3A4 and P-gp (eg rifampin) decrease apixaban levels increasing stroke risk Risk of serious and fatal bleeding discontinue if active bleeding occurs.
| Breastfeeding | No human data; apixaban is excreted in rat milk, but M/P ratio unknown. Breastfeeding is not recommended due to risk of bleeding in infant and lack of safety data. |
| Teratogenic Risk | Apixaban is contraindicated in pregnancy due to risk of hemorrhage. Animal studies show no teratogenicity, but human data insufficient. First trimester: potential risk of miscarriage and bleeding; second trimester: risk of placental abruption; third trimester: risk of maternal-fetal hemorrhage, premature labor, fetal death. Use only if no alternative anticoagulant. |
■ FDA Black Box Warning
Increased risk of thrombotic events if prematurely discontinued. Epidural or spinal hematomas in patients receiving neuraxial anesthesia or undergoing spinal puncture.
| Common Effects | VTE treatment |
| Serious Effects |
Active pathological bleeding; severe hypersensitivity to apixaban; strong dual inhibitors of CYP3A4 and P-glycoprotein (e.g., ketoconazole, itraconazole, ritonavir) in patients with mechanical heart valves or moderate to severe mitral stenosis.
| Precautions | Increased risk of bleeding; spinal/epidural hematoma; discontinuation for surgery or invasive procedures; prosthetic heart valves; antiphospholipid syndrome; renal impairment; pregnancy and lactation. |
| Food/Dietary | No specific food interactions requiring dietary restrictions. Apixaban can be taken with or without food. Grapefruit juice has not been shown to cause clinically significant interaction with apixaban. Maintain consistent intake of vitamin K-rich foods if on warfarin, but not applicable to apixaban. Avoid excessive alcohol consumption due to bleeding risk. |
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| Fetal Monitoring | Monitor maternal CBC for anemia, signs of bleeding (hematuria, GI bleeding, ecchymosis). Fetal monitoring via ultrasound for growth and amniotic fluid volume, plus serial non-stress tests. Monitor for placental abruption. |
| Fertility Effects | No effects on fertility in animal studies; no human data. Apixaban does not affect reproductive hormones, but any severe bleeding event could temporarily impair fertility. |
| Clinical Pearls | Apixaban requires dose reduction to 2.5 mg twice daily in patients with at least two of the following: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. Avoid use in patients with mechanical heart valves or moderate-to-severe mitral stenosis. No routine anticoagulation monitoring needed; anti-Factor Xa assay can be used if necessary. Reversal agent: andexanet alfa. Apixaban is not recommended in patients with CrCl <15 mL/min or on dialysis. Strong CYP3A4 and P-gp inducers (e.g., rifampin, phenytoin) reduce apixaban exposure; avoid concomitant use. Strong dual inhibitors of CYP3A4 and P-gp (e.g., ketoconazole, ritonavir) increase exposure; reduce dose if already on reduced dose or avoid if on standard dose. |
| Patient Advice | Take apixaban exactly as prescribed, twice daily, with or without food. · Do not miss doses; if a dose is missed, take it as soon as possible on the same day and resume regular schedule. Do not double dose. · Inform all healthcare providers that you are taking apixaban, especially before surgery or dental procedures. · Watch for signs of bleeding: unusual bruising, nosebleeds, prolonged bleeding from cuts, blood in urine or stool, coughing up blood, or heavy menstrual bleeding. · Seek emergency care for severe bleeding, head injury, or inability to stop bleeding. · Do not stop apixaban without consulting your doctor; stopping increases risk of blood clots. · Avoid alcohol in excess as it can increase bleeding risk. · Tell your doctor about all medications, including over-the-counter drugs and herbal supplements, especially aspirin, NSAIDs, and St. John's wort. |