Generic Name

Xarelto (rivaroxaban)

Mechanism

Xarelto (rivaroxaban) is a direct Factor Xa inhibitor. It selectively and reversibly blocks the active site of Factor Xa, thereby inhibiting the conversion of prothrombin to thrombin and halting the final steps of the coagulation cascade. Unlike vitamin‑K antagonists, it does not require monitoring of coagulation parameters and has a predictable dose‑response relationship.

Pharmacokinetics

• Absorption: Peak plasma concentrations reached in 2–4 h; 66 % bioavailability when taken with food.
• Distribution: Highly protein‑bound (≈ 85 %) with modest volume of distribution (~ 50 L).
• Metabolism & Excretion: Metabolized via CYP3A4/5, CYP2J2, and CYP2C8; partially cleared by kidney (≈ 35 %) and liver (≈ 65 %).
• Half‑life: 5–9 h in healthy adults; 11–13 h in patients with renal impairment.
• Drug interactions: Strong P‑gp inhibitors/inducers and CYP3A4 inducers alter exposure (e.g., ketoconazole ↑ exposure; rifampin ↓ exposure).

Indications

• Treatment of acute DVT and PE, with 21 days of 15 mg q24h (≤ 3 days to 15 mg) then 20 mg q24h.
• Prevention of DVT/PE after major orthopedic surgery (2.5 mg q12h for 10 days post‑hip or knee replacement).
• Stroke & systemic embolism prevention in non‑valvular atrial fibrillation (20 mg q24h).
• Treatment & prevention of recurrent DVT/PE in patients with prolonged anticoagulation needs.

Contraindications

• Absolute contraindications: Active bleeding, hypersensitivity to rivaroxaban, severe hepatic impairment (Child‑Pugh C).
• Relative contraindications: Severe renal impairment (CrCl < 15 mL/min), pregnancy (use only if benefits outweigh risks).
• Warnings: Major bleeding risk; use caution with concomitant anticoagulants, antiplatelets, or NSAIDs. No licensed reversal agent; consider PCC or activated PCC if life‑threatening hemorrhage.

Dosing

• Take orally with a full glass of water; food increases absorption.
• Continue therapy for ≥ 6 months for DVT/PE unless contraindicated.

Adverse Effects

• Common: Nausea, dyspepsia, hematuria, anemia, bruising.
• Serious: Major GI bleeding, intracranial hemorrhage, thrombocytopenia, hypersensitivity reactions.
• Rare: Hepatic injury, tendon rupture (low‑risk).
• Bleeding risk modifiers: Age >75 yrs, renal dysfunction, concomitant antithrombotic drugs, high alcohol intake.

Monitoring

• Routine coagulation labs not required for routine therapy.
• Baseline: CBC, CMP, CrCl.
• Follow‑up: Re‑check LFTs and renal function after 3 months, then annually.
• In anticoagulant overlap or bridging: Do not use INR; monitor bleeding signs.
• Special case: If renal/hepatic function changes markedly, adjust dose accordingly.
• Procedural planning: Stop 24–48 h prior to low‑risk surgery; 48–72 h for high‑risk.

Clinical Pearls

• No routine monitoring: Rivaroxaban’s pharmacokinetics allow omission of PT/INR, reducing clinic visits—great for patients in remote areas.
• Use with P‑gp/CYP3A4 inhibitors: Ketoconazole or clarithromycin can nearly double exposure; consider dose reduction or avoid. Conversely, rifampin decreases levels—use 10‑mg regimen with caution.
• Tissue factor‑triggered coagulation assays may underestimate effect; point‑of‑care anti‑Xa assays timed at 4–6 h post‑dose give the most reliable snapshot.
• Peri‑operative cessation: For elective procedures, 24–48 h holds suffice; for urgent surgery, administer 4‑10 mg PCC (if available) to mitigate hemorrhage.
• Frailty & fall risk: In elderly with fall risk, favor low-dose 2.5 mg BID for surgical prophylaxis to balance thrombosis/bleed risk.
• Pregnancy: Data limited; consider warfarin if safe dosage is established; otherwise, alternative mechanical prophylaxis.
• Drug‑specific: Rivaroxaban is not recommended in patients with mechanical heart valves; use a vitamin‑K antagonist or low‑molecular‑weight heparin instead.

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• *This drug card covers key pharmacologic concepts and practical guidance for Xarelto (rivaroxaban), enabling efficient review for medical students and clinicians alike.*