Direct%2525252525252520oral%2525252525252520anticoagulants

# Direct Oral Anticoagulants (DOACs) ## Overview Direct oral anticoagulants (DOACs) include direct thrombin inhibitors (dabigatran) and Factor Xa inhibitors (apixaban, rivaroxaban, edoxaban). They offer a predictable pharmacokinetic profile, fixed dosing, and minimal food/drug interactions compared to warfarin, eliminating the need for routine INR monitoring. ## Primary Indications * Non-valvular atrial fibrillation (stroke/systemic embolism prophylaxis). * Treatment and secondary prophylaxis of deep vein thrombosis (DVT) and pulmonary embolism (PE). * Prophylaxis of DVT/PE following hip or knee replacement surgery. ## Adult Dosing * **Apixaban (Eliquis):** * Afib: 5 mg PO BID. (Reduce to 2.5 mg BID if ≥2 of: age ≥80, weight ≤60 kg, or Scr ≥1.5 mg/dL). * VTE Rx: 10 mg PO BID for 7 days, then 5 mg PO BID. * **Rivaroxaban (Xarelto):** * Afib: 20 mg PO daily with evening meal. * VTE Rx: 15 mg PO BID for 21 days, then 20 mg PO daily. * **Dabigatran (Pradaxa):** * Afib: 150 mg PO BID. * VTE Rx: 150 mg PO BID (after 5-10 days of parenteral anticoagulation). * **Edoxaban (Savaysa):** * Afib/VTE Rx: 60 mg PO daily. ## Pediatric Dosing Dosing is highly variable based on weight and age; generally weight-based protocols (e.g., ARCH guidelines) are used. * **Dabigatran:** Indicated for venous thromboembolism (pediatric patients 3 months to <18 years). Dosing is based on nomograms using BSA and weight. * **Rivaroxaban:** Approved for DVT/PE prophylaxis and treatment in children ≥1 month. * *Note: Consult institution-specific pediatric hematology protocols.* ## Dose Adjustments * **Renal Impairment:** Mandatory dose reductions or contraindications based on CrCl (Cockcroft-Gault). * Rivaroxaban/Edoxaban generally require dose reduction or discontinuation at CrCl <30 mL/min (or <15 for edoxaban). * Apixaban: No adjustment unless meeting specific "Dose Reduction" criteria above. * **Hepatic Impairment:** Avoid or exercise caution in Child-Pugh B or C. ## Contraindications * Active pathological bleeding. * Mechanical heart valves (dabigatran is strictly contraindicated). * Moderate-to-severe hepatic impairment (Child-Pugh B/C). * Severe renal impairment (CrCl <15–30 mL/min depending on specific agent). ## Adverse Effects * Major and minor bleeding (GI bleeding risk is higher with rivaroxaban/dabigatran compared to warfarin). * Dyspepsia/gastritis (notably with dabigatran due to tartaric acid core). * Elevated LFTs (rare). ## Key Drug Interactions * **Strong Dual Inhibitors/Inducers:** Avoid concomitant use with strong P-gp and strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) or inducers (e.g., carbamazepine, rifampin). * **Antiplatelets/NSAIDs:** Increased bleeding risk. ## Monitoring * **Baseline:** CBC, baseline renal function (Scr/CrCl), LFTs, and PT/aPTT. * **Ongoing:** Annual renal/hepatic function tests. No routine coagulation monitoring required; however, specific assays (e.g., Anti-Xa for FXa inhibitors, ecarin clotting time for dabigatran) may be used in urgent settings or surgery. ## Clinical Pearls * **Transitioning:** DOACs have rapid onset; initiate once parenteral anticoagulation is stopped (or per specific switch protocols). * **Non-valvular Afib:** DOACs are ineffective in patients with mechanical heart valves or moderate-to-severe mitral stenosis. * **Adherence:** Due to short half-lives, missed doses significantly increase stroke risk. * **Reversal:** Use Andexanet alfa for apixaban/rivaroxaban and Idarucizumab for dabigatran in life-threatening bleeding. *** **Educational Disclaimer:** This information is for educational purposes only. Always consult current institutional protocols, the package insert, and clinical decision support tools before prescribing or administering medication.