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# Direct Oral Anticoagulants (DOACs)
## Overview
DOACs include Factor Xa inhibitors (apixaban, rivaroxaban, edoxaban) and direct thrombin inhibitors (dabigatran). They provide predictable anticoagulation without the need for routine INR monitoring, offering a fixed-dosing approach 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).
* Reduction in the risk of recurrent DVT/PE following initial therapy.
* Prophylaxis of DVT/PE following hip or knee replacement surgery.
## Adult Dosing
* **Apixaban (Eliquis):** AFib: 5 mg BID. DVT/PE: 10 mg BID for 7 days, then 5 mg BID.
* **Rivaroxaban (Xarelto):** AFib: 20 mg daily. DVT/PE: 15 mg BID for 21 days, then 20 mg daily.
* **Dabigatran (Pradaxa):** AFib/DVT/PE: 150 mg BID; 75 mg BID for select renal impairment.
* **Edoxaban (Savaysa):** AFib: 60 mg daily (do not use if CrCl > 95 mL/min). DVT/PE: 60 mg daily after parenteral bridge.
## Pediatric Dosing
Dosing is weight-based. Protocols mandate the use of weight-based nomograms (e.g., CHEST guidelines or institutional-specific protocols). **Off-label use is common; consult pediatric hematology specialists for exact mg/kg calculations.**
## Dose Adjustments
Adjustments are primarily renal-based.
* **Apixaban:** Reduce to 2.5 mg BID if ≥ 2 of following: age ≥ 80, weight ≤ 60 kg, or SCr ≥ 1.5 mg/dL.
* **Rivaroxaban/Dabigatran/Edoxaban:** Contraindicated or require significant dose reduction in patients with CrCl < 30 mL/min (or < 15 mL/min depending on the specific agent).
* **Hepatic impairment:** Use caution; avoid in Child-Pugh B or C.
## Contraindications
* Active pathological bleeding.
* Mechanical prosthetic heart valves (dabigatran contraindicated; others generally avoided).
* Moderate-to-severe hepatic impairment.
* Hypersensitivity to the agent.
## Adverse Effects
* Major and minor bleeding (GI, intracranial, mucosal).
* Dyspepsia (common with dabigatran).
* Anemia.
* Elevated liver enzymes (rare).
## Key Drug Interactions
* **Strong Dual Inhibitors/Inducers of P-gp and CYP3A4:** Concomitant use with drugs like ketoconazole, ritonavir, rifampin, or phenytoin significantly alters DOAC plasma levels.
* **Antiplatelets/NSAIDs:** Increased risk of major bleeding.
* **SSRI/SNRIs:** Increased risk of bleeding due to platelet serotonin depletion.
## Monitoring
* **Baseline/Periodic:** Renal function (CrCl via Cockcroft-Gault), LFTs, CBC (to monitor for overt bleeding or anemia).
* **Coagulation Tests:** Routine monitoring is not required. Anti-Xa assays (for Xa inhibitors) and Thrombin Time or ecarin clotting time (for dabigatran) provide semi-quantitative data in emergency settings.
## Clinical Pearls
* **Adherence is critical:** Short half-lives make missed doses high-risk for thromboembolism.
* **Reversal Agents:** Idarucizumab is available for dabigatran; Andexanet alfa is available for apixaban and rivaroxaban.
* **Transitioning:** Utilize institutional protocols for switching between warfarin and DOACs (based on INR values).
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**Educational Disclaimer:** This information is for educational purposes only. Clinical guidelines and prescribing information change frequently. Always verify current dosage, contraindications, and drug interaction data via local institutional protocols, electronic health record prescribing alerts, or current official FDA-approved package inserts before prescribing or administering medication.
