Apixa

Approved Indications:

• Prevention of Stroke and Systemic Embolism in Non-Valvular Atrial Fibrillation (NVAF):
  For patients with NVAF at risk for stroke or systemic embolism.
• Treatment of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE):
  For the initial treatment and continued therapy of acute DVT and PE.
• Prevention of Recurrent DVT and PE:
  For reducing the risk of recurrent DVT and PE following initial therapy.
• Prophylaxis of Venous Thromboembolism (VTE) after Hip or Knee Replacement Surgery:
  To prevent postoperative VTE in adults undergoing elective hip or knee replacement.

Important Off-Label or Clinically Accepted Uses:

• Extended prophylaxis in medically ill patients at risk for thromboembolism (investigational or per specific guidelines).
• Use in patients with cancer-associated thrombosis under specialist guidance (off-label in some regions).

Adults:

• Non-valvular Atrial Fibrillation (Stroke Prevention):
  5 mg orally twice daily.
  Dose reduction to 2.5 mg twice daily for patients meeting ≥2 of the following: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL.
• Treatment of DVT and PE:
  10 mg orally twice daily for the first 7 days, followed by 5 mg twice daily.
• Prevention of Recurrent DVT and PE:
  2.5 mg orally twice daily after at least 6 months of treatment.
• VTE Prophylaxis Post Hip or Knee Replacement Surgery:
  2.5 mg orally twice daily, starting 12–24 hours after surgery, continued for 12 days (knee) or 35 days (hip).

Pediatrics:

• Safety and efficacy not established.

Elderly:

• No initial dose adjustment; dose reductions as above apply based on renal function and clinical factors.

Renal Impairment:

• Mild to Moderate (CrCl ≥30 mL/min): No adjustment needed.
• Severe (CrCl 15–29 mL/min): Use with caution; avoid if CrCl <15 mL/min or on dialysis.

Hepatic Impairment:

• Avoid use in patients with moderate to severe hepatic impairment (Child-Pugh B or C) or with coagulopathy.

Administration:

• Oral route only.
• Can be taken with or without food.
• Swallow tablets whole; do not crush or chew.

Apixaban is a selective, direct, reversible inhibitor of activated Factor Xa (FXa), a key enzyme in the coagulation cascade. By inhibiting FXa, apixaban prevents the conversion of prothrombin to thrombin, reducing thrombin generation and subsequent fibrin clot formation. This anticoagulant effect disrupts the coagulation process, thereby preventing thrombosis without directly affecting platelet aggregation.

• Absorption:
  Oral bioavailability approximately 50%; peak plasma concentrations achieved 3–4 hours post-dose.
• Distribution:
  Volume of distribution approximately 21 L; highly protein-bound (~87%).
• Metabolism:
  Metabolized primarily via CYP3A4/5 with minor contributions from CYP1A2, 2C8, 2C9, 2C19, and 2J2.
• Elimination:
  Half-life approximately 12 hours.
  Excretion routes: ~25% renal; remainder via feces and metabolism.
• Steady-State:
  Achieved within 3 days of twice-daily dosing.

• Pregnancy:
  No FDA pregnancy category assigned; limited human data. Animal studies indicate potential for fetal harm. Use only if clearly needed.
• Lactation:
  Unknown if excreted in human milk; breastfeeding not recommended during treatment.
• Caution:
  Use only when benefits outweigh risks.

• Primary Class: Anticoagulant
• Subclass: Direct oral anticoagulant (DOAC), direct Factor Xa inhibitor.

• Active pathological bleeding.
• Severe hypersensitivity to apixaban or any excipients.
• Hepatic disease associated with coagulopathy and clinically relevant bleeding risk.
• Mechanical prosthetic heart valves (not indicated).
• Concomitant use with other anticoagulants (except under specific monitored settings).

• Bleeding Risk:
  Increased risk of serious and potentially fatal bleeding; monitor closely.
• Spinal/Epidural Hematoma:
  Risk in patients undergoing neuraxial anesthesia or spinal puncture; monitor neurological status.
• Renal Impairment:
  Use caution; increased bleeding risk in severe impairment.
• Hepatic Impairment:
  Avoid in moderate to severe impairment.
• Discontinuation:
  Risk of thrombotic events if stopped abruptly; consider bridging if appropriate.

• Common:
  Bleeding events including minor bleeding, bruising, epistaxis, and gastrointestinal bleeding.
• Serious:
  Major bleeding (intracranial, gastrointestinal), hypersensitivity reactions.
• Rare:
  Anemia, thrombocytopenia.
• Onset & Dose-Dependence:
  Bleeding risk increases with higher doses and concurrent use of other anticoagulants or antiplatelet agents.

• CYP3A4 and P-glycoprotein (P-gp) substrates:
  Strong inhibitors (e.g., ketoconazole, ritonavir) increase apixaban levels → increased bleeding risk.
  Strong inducers (e.g., rifampin, carbamazepine) decrease apixaban levels → reduced efficacy.
• Anticoagulants and Antiplatelets:
  Additive bleeding risk with agents like aspirin, NSAIDs, clopidogrel.
• Food & Alcohol:
  No significant food interaction. Alcohol may increase bleeding risk.

• FDA (2022):
  Updated labeling highlights bleeding risks and recommends caution in renal impairment.
• NICE and ESC Guidelines (2023):
  Endorsed apixaban as first-line oral anticoagulant for stroke prevention in NVAF and treatment of VTE.
• EMA:
  Supports expanded indications and dosing adjustments based on renal function.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in original container until use.
• Do not freeze.
• Keep out of reach of children.