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# Direct Oral Anticoagulants (DOACs)
## Overview
DOACs include Factor Xa inhibitors (apixaban, rivaroxaban, edoxaban) and a direct thrombin inhibitor (dabigatran). They provide predictable anticoagulation without 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/knee replacement surgery.
## Adult Dosing
* **Apixaban:** AFib: 5 mg BID. DVT/PE: 10 mg BID for 7 days, then 5 mg BID.
* **Rivaroxaban:** AFib: 20 mg daily with the evening meal. DVT/PE: 15 mg BID for 21 days, then 20 mg daily.
* **Dabigatran:** AFib: 150 mg BID. DVT/PE: 150 mg BID (following ≥5 days of parenteral anticoagulation).
* **Edoxaban:** AFib: 60 mg daily. DVT/PE: 60 mg daily (following ≥5 days of parenteral anticoagulation).
## Pediatric Dosing
Dosing is age/weight-based. Use is generally restricted to specialized centers or FDA-approved protocols (e.g., age ≥3 months). **Consult institutional protocols and current guidelines (e.g., ASH or CHEST) as dosing is weight-tapped and requires parenteral bridge.** DO NOT initiate without pediatric hematology consultation.
## Dose Adjustments
* **Renal Impairment:** Required for all agents based on CrCl. Use with extreme caution or avoid in end-stage renal disease (dialysis status varies by agent; apixaban has limited data, others generally contraindicated).
* **Hepatic Impairment:** Contraindicated in Child-Pugh B or C (varies by agent).
* **Apixaban:** Reduce to 2.5 mg BID if ≥2 of: age ≥80, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL.
## Contraindications
* Active pathological bleeding.
* Mechanical prosthetic heart valves (dabigatran contraindicated in all; others generally avoided).
* Moderate-to-severe hepatic impairment (Child-Pugh B/C).
* Hypersensitivity to the specific agent.
## Adverse Effects
* Major and clinically relevant non-major bleeding.
* Gastrointestinal distress (common with dabigatran).
* Elevated liver enzymes (rare).
## Key Drug Interactions
* **P-gp and Strong CYP3A4 inhibitors/inducers:** Co-administration (e.g., ketoconazole, rifampin, phenytoin, carbamazepine) significantly alters plasma concentrations and should be avoided or managed with caution.
* **Antiplatelets/NSAIDs:** Increased bleeding risk; avoid dual therapy unless clearly indicated (e.g., ACS).
## Monitoring
* **Baseline:** CBC, renal function (CrCl), liver function tests (LFTs), and coagulation panel (PT/aPTT - note that DOACs do not correlate linearly with these tests).
* **Ongoing:** Annual renal function assessment (more frequent in elderly/CKD). Adherence is critical due to short half-lives.
## Clinical Pearls
* **Reversal:** Idarucizumab is specific for dabigatran. Andexanet alfa is indicated for reversal of apixaban/rivaroxaban.
* **Missed Doses:** Review institutional protocol; general rule for daily dosing is to take as soon as remembered if before the next scheduled dose. Never double the dose.
* **Transitioning:** Utilize standard conversion protocols when switching from warfarin (target INR <2.0).
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*Disclaimer: This information is for educational purposes. Dosing and clinical practices vary by institution and local formularies. Always verify current prescribing information, package inserts, and hospital guidelines before prescribing or administering medications.*
