Usage
- Apixaban is prescribed for the prevention and treatment of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). It is also used to prevent stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF). It is sometimes prescribed for several days after hip or knee replacement surgery while the patient is unable to walk, as this is a time when blood clots are most likely to form.
- Pharmacological Classification: Apixaban is an anticoagulant, specifically a direct factor Xa inhibitor.
- Mechanism of Action: Apixaban selectively and reversibly inhibits factor Xa, a key enzyme in the coagulation cascade. By inhibiting factor Xa, apixaban prevents the formation of thrombin, thereby reducing the formation of blood clots.
Alternate Names
- International Nonproprietary Name (INN): Apixaban
- Brand Names: Eliquis
How It Works
- Pharmacodynamics: Apixaban exerts its anticoagulant effect by selectively inhibiting factor Xa, which plays a crucial role in the coagulation cascade. This inhibition reduces thrombin generation and ultimately prevents the formation of fibrin clots.
- Pharmacokinetics: Apixaban is rapidly absorbed after oral administration, reaching peak plasma concentrations within 3 to 4 hours. It has a bioavailability of approximately 50%. Apixaban is metabolized primarily via CYP3A4/5 with minor contributions from CYP1A2, 2C8, 2C9, 2C19, and 2J2. It is eliminated through multiple pathways, including renal excretion (approximately 27% as unchanged drug) and hepatic metabolism with biliary/fecal excretion. It has a half-life of about 12 hours.
- Mode of Action: Apixaban directly binds to the active site of factor Xa, preventing it from converting prothrombin to thrombin.
- Receptor Binding/Enzyme Inhibition: Apixaban’s mechanism of action involves direct, selective, and reversible inhibition of free and clot-bound factor Xa. No direct receptor binding is involved.
- Elimination Pathways: Apixaban is eliminated through both renal and hepatic routes. About 27% of the drug is excreted unchanged in the urine, while the remainder is metabolized by CYP3A4/5 (primarily) and other CYP enzymes and subsequently eliminated in the feces via biliary excretion.
Dosage
Standard Dosage
Adults:
- NVAF: 5 mg twice daily.
- DVT/PE: 10 mg twice daily for 7 days, followed by 5 mg twice daily.
- Post-surgical thromboprophylaxis (hip/knee replacement): 2.5 mg twice daily.
Children: Apixaban is not approved for use in pediatric patients except for treatment of VTE in patients weighing ≥ 35 kg and some specific pediatric uses off label. The dose is weight based.
Special Cases:
- Elderly Patients (≥ 80 years) or patients with a body weight ≤ 60 kg or serum creatinine ≥ 1.5 mg/dL: 2.5 mg twice daily for NVAF.
- Patients with Renal Impairment (moderate, CrCl 15-29 mL/min): 2.5 mg twice daily.
- Patients with Hepatic Dysfunction (moderate): Use with caution; no dose adjustment is recommended for mild to moderate hepatic impairment but Apixaban is not recommended in patients with severe hepatic impairment (Child-Pugh C).
- Patients with Comorbid Conditions: Dose adjustments may be necessary based on specific comorbid conditions and concomitant medications.
Clinical Use Cases
Dosages provided above apply to the clinical use cases of NVAF, DVT/PE treatment, and thromboprophylaxis after hip/knee surgery. Dosages for other procedures/conditions not addressed in the sources.
Dosage Adjustments
- Dose adjustments are required for elderly patients, patients with low body weight, renal impairment, and those taking interacting medications. Refer to the “Special Cases” section above.
Side Effects
Common Side Effects
- Bleeding (e.g., nosebleeds, easy bruising, increased menstrual bleeding)
- Nausea
- Hematuria
- Anemia
- Dizziness
- Rash
Rare but Serious Side Effects
- Intracranial hemorrhage
- Gastrointestinal bleeding
- Spinal/epidural hematoma (especially in patients with epidural catheters)
Long-Term Effects
- Long-term use may increase the risk of osteoporosis.
Adverse Drug Reactions (ADR)
- Any signs of serious bleeding (e.g., blood in urine or stool, severe headache, neurological symptoms) require immediate medical attention.
- Allergic reactions (e.g., angioedema, urticaria)
Contraindications
- Active pathological bleeding
- Severe hypersensitivity to apixaban
- Hepatic disease associated with coagulopathy and a clinically relevant bleeding risk (including severe hepatic impairment)
Drug Interactions
- CYP3A4 Inhibitors/Inducers: Strong inhibitors (e.g., ketoconazole, ritonavir) and inducers (e.g., rifampin, phenytoin) of CYP3A4 can increase and decrease apixaban levels, respectively.
- Anticoagulants/Antiplatelets: Concomitant use with other anticoagulants (e.g., warfarin, heparin) or antiplatelets (e.g., aspirin, clopidogrel) increases the risk of bleeding.
- NSAIDs: Nonsteroidal anti-inflammatory drugs (NSAIDs) can increase the risk of bleeding.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: There is no established FDA Pregnancy Safety Category for apixaban; sources suggest it has shown potential for fetal risk in some animal models, and apixaban has been assigned pregnancy category C in other jurisdictions. Apixaban is generally not recommended during pregnancy.
- Breastfeeding: Apixaban may be excreted in human milk. Due to potential risks to the infant, breastfeeding is not recommended while taking apixaban.
Drug Profile Summary
- Mechanism of Action: Direct factor Xa inhibitor.
- Side Effects: Bleeding, nausea, anemia, dizziness, rash.
- Contraindications: Active bleeding, hypersensitivity, severe hepatic impairment.
- Drug Interactions: CYP3A4 inhibitors/inducers, other anticoagulants/antiplatelets, NSAIDs.
- Pregnancy & Breastfeeding: Not recommended during pregnancy or breastfeeding.
- Dosage: Refer to dosage section above.
- Monitoring Parameters: No routine monitoring is typically required; however, factor Xa activity levels can be measured if needed.
Popular Combinations
- Apixaban is often used as monotherapy. Combination use with other anticoagulants or antiplatelets is generally avoided due to the increased risk of bleeding.
Precautions
- General Precautions: Assess for bleeding risk factors, renal and hepatic function before initiating therapy.
- Specific Populations: Use with caution in elderly patients, patients with renal or hepatic impairment, and pregnant/breastfeeding women.
- Lifestyle Considerations: Patients should avoid activities that increase bleeding risk. Alcohol consumption should be limited.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Apixaban?
A: The dosage depends on the indication. For NVAF, it is 5 mg twice daily, reduced to 2.5 mg twice daily in specific patient populations. For DVT/PE treatment, it is 10 mg twice daily for 7 days followed by 5 mg twice daily. Post hip or knee replacement, the dose is 2.5 mg twice daily.
Q2: What are the most common side effects?
A: Bleeding (e.g., nosebleeds, bruising, hematuria) and nausea.
Q3: What are the contraindications for apixaban?
A: Active bleeding, hypersensitivity to apixaban, and severe hepatic impairment.
Q4: How does apixaban interact with other medications?
A: It can interact with CYP3A4 inhibitors/inducers, other anticoagulants/antiplatelets, and NSAIDs.
Q5: Can apixaban be used during pregnancy or breastfeeding?
A: It is generally not recommended during pregnancy or breastfeeding.
Q6: How is apixaban eliminated from the body?
A: Through both renal and hepatic routes (renal excretion of unchanged drug and hepatic metabolism followed by fecal excretion).
Q7: What is the mechanism of action of apixaban?
A: Apixaban is a direct factor Xa inhibitor.
Q8: What should I do if a patient experiences a major bleeding event while taking apixaban?
A: Discontinue apixaban immediately and provide supportive care. There is no specific reversal agent readily available, but consider administering prothrombin complex concentrate (PCC), activated PCC or recombinant factor VIIa, if needed. Consult a hematologist immediately.
Q9: What should I counsel my patients on regarding lifestyle while on Apixaban?
A: Advise patients to avoid activities that increase bleeding risk, inform all healthcare providers that they are taking Apixaban, and limit alcohol intake. Provide them with a medical alert bracelet indicating Apixaban use. They should also report any signs or symptoms of unusual bleeding immediately.
