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# Direct Oral Anticoagulants (DOACs)
## Overview
DOACs include Direct Factor Xa inhibitors (apixaban, rivaroxaban, edoxaban) and the Direct Thrombin inhibitor (dabigatran). They offer fixed dosing, predictable pharmacokinetics, and no required routine coagulation monitoring compared to warfarin.
## Primary Indications
* Prevention of stroke/systemic embolism in non-valvular atrial fibrillation (NVAF).
* Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE).
* Prophylaxis of DVT following hip or knee replacement surgery.
## Adult Dosing
* **Apixaban (Eliquis):** AFib: 5 mg PO BID. DVT/PE: 10 mg BID for 7 days, then 5 mg BID.
* **Rivaroxaban (Xarelto):** AFib: 20 mg PO daily with evening meal. DVT/PE: 15 mg BID for 21 days, then 20 mg daily.
* **Dabigatran (Pradaxa):** AFib/DVT/PE: 150 mg PO BID (following 5-10 days of parenteral anticoagulation for DVT/PE).
* **Edoxaban (Savaysa):** AFib/DVT/PE: 60 mg PO daily (after 5-10 days of parenteral anticoagulation for DVT/PE).
## Pediatric Dosing
Dosing is weight and age-adjusted and off-label in many jurisdictions; utilize institutions-specific protocols (e.g., CHEST guidelines). Rivaroxaban and dabigatran have FDA-approved pediatric formulations for VTE treatment based on body surface area (BSA) or weight-based nomograms. **Consult pediatric hematology guidelines before prescription.**
## Dose Adjustments
* **Renal:** Mandatory for all DOACs. Apixaban: Reduce to 2.5 mg BID if ≥2 of the following: Age ≥80, Weight ≤60 kg, or Scr ≥1.5 mg/dL. Rivaroxaban/Edoxaban/Dabigatran: Contraindicated or dose-reduced in severe renal impairment (CrCl <15–30 mL/min).
* **Hepatic:** Avoid rivaroxaban and edoxaban in moderate-to-severe hepatic impairment (Child-Pugh B/C).
## Contraindications
* Active pathological bleeding.
* Mechanical prosthetic heart valves.
* Significant mitral stenosis.
* Hypersensitivity to the specific agent.
## Adverse Effects
* Major and minor bleeding (GI, intracranial).
* Dyspepsia (common with dabigatran).
* Elevated liver enzymes (rare).
## Key Drug Interactions
* **CYP3A4/P-gp inhibitors/inducers:** Avoid concomitant use of strong inhibitors or inducers (e.g., ketoconazole, rifampin, carbamazepine, phenytoin) as they significantly alter plasma concentrations.
* **Antiplatelets/NSAIDs:** Increased bleeding risk; use with caution.
## Monitoring
* Baseline and periodic Renal Function (CrCl via Cockcroft-Gault), CBC (Hgb/Hct), and LFTs.
* No routine INR monitoring required.
* *Note:* In life-threatening bleeding, contact a specialized hematology center regarding specialized assays (e.g., anti-Xa activity) or reversal agents (Idarucizumab for dabigatran; Andexanet alfa for Factor Xa inhibitors).
## Clinical Pearls
* **Adherence:** Half-lives are short; missed doses significantly increase thrombosis risk.
* **Rivaroxaban:** Must be taken with food for the 15/20 mg doses to ensure adequate absorption.
* **Edoxaban:** Do not use for NVAF in patients with CrCl >95 mL/min (increased stroke risk vs. warfarin).
* **Surgery:** Generally hold 24–48 hours before elective procedures, depending on renal function and bleeding risk of the procedure.
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**Educational Disclaimer:** This information is for educational purposes only. Always verify drug dosages, contraindications, and interaction profiles by consulting current prescribing information (package inserts), institutional protocols, or clinical decision support resources, as clinical guidelines change frequently.
