Rivaroxaban

# Rivaroxaban ## Overview - **Classification**: Direct Oral Anticoagulant (DOAC), Factor Xa Inhibitor - **Mechanism**: Selectively inhibits Factor Xa, preventing thrombin generation and clot formation. Does not require antithrombin III monitoring. ## Primary Indications 1. **Nonvalvular Atrial Fibrillation (NVAF)**: Reduction of stroke and systemic embolism risk. 2. **Treatment of DVT/PE**: Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). 3. **Prevention of DVT/PE**: After hip or knee replacement surgery. 4. **Prevention of DVT/PE Recurrence**: In patients at continued risk. 5. **Coronary Artery Disease (CAD)/Peripheral Artery Disease (PAD)**: Reduction of major CV events in high-risk patients (in combination with aspirin). 6. **Pediatric VTE**: Treatment of VTE and prevention of VTE recurrence (after initial parenteral anticoagulation). ## Adult Dosing ### Standard Dosing **Nonvalvular Atrial Fibrillation (NVAF)** - **Dose**: **20 mg** - **Frequency**: Once daily (QD) - **Route**: Oral, with the evening meal - **Consideration**: CrCl 15-50 mL/min: **15 mg** QD with evening meal. **Treatment of DVT/PE** - **Dose**: **15 mg** - **Frequency**: Twice daily (BID) for the first 21 days - **Route**: Oral, with food - **Follow-up**: Then **20 mg** QD with food for continued treatment. **Prevention of DVT/PE after Hip/Knee Replacement Surgery** - **Hip replacement**: **10 mg** QD for **35 days** - **Knee replacement**: **10 mg** QD for **12 days** - **Route**: Oral, with or without food. **Prevention of DVT/PE Recurrence** - **Dose**: **10 mg** - **Frequency**: Once daily (QD) - **Route**: Oral, with or without food - **Consideration**: After at least 6 months of initial anticoagulant treatment. **CAD/PAD (Reduction of major CV events)** - **Dose**: **2.5 mg** - **Frequency**: Twice daily (BID) - **Route**: Oral, with or without food - **Combination**: Used with aspirin **75-100 mg** QD. ### Dose Adjustments - **Renal Impairment**: - **CrCl >50 mL/min**: No adjustment. - **CrCl 15-50 mL/min**: Adjust for NVAF (**15 mg** QD). For DVT/PE treatment, continue **20 mg** QD after 21 days; for prophylaxis/CAD/PAD, no adjustment. - **CrCl <15 mL/min**: Avoid use. Consider risks/benefits if no other options. - **Hepatic Impairment**: - **Child-Pugh A**: No adjustment. - **Child-Pugh B or C**: Avoid use (increased bleeding risk). - **Elderly Patients**: - Increased bleeding risk, monitor closely. No specific dose adjustment based on age alone. ## Pediatric Dosing *(Approved for VTE treatment and prevention of VTE recurrence after at least 5 days of initial parenteral anticoagulation)* ### Neonates (0-28 days) - **Indication**: VTE treatment/recurrence prevention. - **Dose**: Oral suspension (administer with food). - **2.5 to <3 kg**: **0.8 mg** BID - **3 to <7 kg**: **1.2 mg** BID - **7 to <12 kg**: **1.6 mg** BID - **Frequency**: Twice daily (BID) - **Maximum**: Weight-based dose. - **Special Notes**: Use oral syringe or NG/gastrostomy tube for administration. ### Infants (1-12 months) - **Indication**: VTE treatment/recurrence prevention. - **Dose**: Oral suspension (administer with food). - **3 to <7 kg**: **1.2 mg** BID - **7 to <12 kg**: **1.6 mg** BID - **12 to <30 kg**: **2 mg** BID - **Frequency**: Twice daily (BID) - **Maximum**: Weight-based dose. - **Special Notes**: Use oral syringe or NG/gastrostomy tube for administration. ### Children (1-12 years) - **Indication**: VTE treatment/recurrence prevention. - **Dose**: Oral suspension or tablets (administer with food). - **12 to <30 kg**: **2 mg** BID - **30 to <50 kg**: **5 mg** BID - **≥50 kg**: **10 mg** BID - **Frequency**: Twice daily (BID) - **Maximum**: **10 mg** BID for children <50 kg. - **Special Notes**: Tablets may be considered for children ≥30 kg if able to swallow. ### Adolescents (13-18 years) - **Indication**: VTE treatment/recurrence prevention. - **Dose**: - **<50 kg**: **10 mg** BID with food. - **≥50 kg**: Initial: **15 mg** BID for 21 days, then **20 mg** QD with food. - **Frequency**: BID, then QD for ≥50 kg. - **Maximum**: Adult doses for ≥50 kg patients. ## Safety Information ### Contraindications - **Absolute**: Active pathological bleeding (e.g., major GI bleed, intracranial hemorrhage). - **Absolute**: Severe hypersensitivity reaction to rivaroxaban. - **Absolute**: Severe hepatic impairment (Child-Pugh B and C) with coagulopathy. - **Absolute**: Concomitant use with other anticoagulants (except during switch therapy). - **Absolute**: Artificial heart valves. ### Common Adverse Effects - **Very Common (>10%)**: Bleeding (various sites, e.g., nosebleed, gum bleed), anemia. - **Common (1-10%)**: Nausea, abdominal pain, dyspepsia, increased transaminases, peripheral edema. - **Serious but Rare**: Major bleeding (intracranial, retroperitoneal), epidural/spinal hematoma (with neuraxial anesthesia), anaphylactic reactions. ### Key Drug Interactions - **Strong CYP3A4 and P-gp inhibitors (e.g., ketoconazole, itraconazole, ritonavir, cobicistat)**: Significantly increase rivaroxaban exposure; **avoid concomitant use**. - **Strong CYP3A4 and P-gp inducers (e.g., rifampin, phenytoin, carbamazepine, St. John's Wort)**: Significantly decrease rivaroxaban exposure; **avoid concomitant use**. - **Other Anticoagulants (e.g., warfarin, heparin, other DOACs)**: Increased bleeding risk; **contraindicated except for switching protocols**. - **Antiplatelet agents (e.g., aspirin, clopidogrel)**: Increased bleeding risk; use with caution. - **NSAIDs**: Increased bleeding risk; use with caution. ## Monitoring & Follow-up - **Before Treatment**: Baseline CBC (Hgb, Hct), renal function (CrCl), hepatic function (ALT/AST). - **During Treatment**: - **Regular monitoring**: Periodically monitor CBC and renal function (e.g., annually, or more frequently if clinically indicated). - **Clinical**: Monitor for any signs or symptoms of bleeding. - **Clinical Signs**: Watch for unexplained bruising, petechiae, epistaxis, hematuria, melena, or severe headache. ## Clinical Pearls - 💡 **Administration with food**: Doses **≥15 mg** must be taken with food. The **10 mg** dose can be taken with or without food. Oral suspension *must* be taken with food. - 💡 **Missed Dose**: If **15 mg BID**, take immediately to ensure 30 mg/day, then resume BID. If **QD**, take immediately that day; do NOT double dose. - 💡 **Reversal Agent**: **Andexanet alfa** is available as a specific reversal agent for life-threatening bleeding. - 💡 **Crushing Tablets**: Tablets can be crushed and mixed with water or apple puree, then administered orally or via NG/gastrostomy tube, immediately followed by food. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.