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# Direct Oral Anticoagulants (DOACs)
## Overview
DOACs include Factor Xa inhibitors (apixaban, rivaroxaban, edoxaban) and the direct thrombin inhibitor (dabigatran). Unlike warfarin, they do not require routine INR monitoring and have fewer dietary interactions.
## 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:** 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. DVT/PE treatment: 10 mg BID x 7 days, then 5 mg BID.
* **Rivaroxaban:** AFib: 20 mg PO daily with evening meal. DVT/PE treatment: 15 mg BID x 21 days, then 20 mg daily.
* **Dabigatran:** AFib: 150 mg PO BID. DVT/PE treatment: 150 mg BID after 5–10 days of parenteral anticoagulation.
* **Edoxaban:** AFib: 60 mg PO daily. Treatment: 60 mg daily after 5–10 days parenteral anticoagulation.
## Pediatric Dosing
Dosing is highly protocol-dependent. Use weight-based regimens (often via nomograms like the ETP-based or anti-Xa based protocols). Apixaban and dabigatran have FDA-approved pediatric formulations for VTE treatment in specific populations; always consult institutional pediatric hematology guidelines before ordering.
## Dose Adjustments
* **Renal Impairment:** Requires dose reductions or avoidance based on CrCl (Cockcroft-Gault). Contraindicated in severe renal impairment (CrCl <15–30 mL/min depending on agent).
* **Hepatic Impairment:** Avoid in moderate-to-severe hepatic impairment (Child-Pugh B or C).
## Contraindications
* Active pathological bleeding.
* Mechanical heart valves (dabigatran contraindicated; others generally avoided).
* Moderate-to-severe hepatic impairment.
* Hypersensitivity.
## Adverse Effects
* Major and minor bleeding (GI, intracranial).
* Anemia.
* Dyspepsia (most common with dabigatran).
* Elevated liver enzymes (rare).
## Key Drug Interactions
* **P-gp and Strong CYP3A4 inhibitors/inducers:** Concomitant use (e.g., ketoconazole, rifampin, phenytoin) significantly alters plasma concentrations.
* **Antiplatelets/NSAIDs/SSRIs:** Increase the risk of major bleeding due to pharmacodynamic synergy.
## Monitoring
* Baseline: CBC, SCr, LFTs, PT/INR, aPTT.
* Ongoing: Periodic renal and hepatic function (at least annually; more frequently in elderly or renal impairment). Assess drug adherence.
* Emergency: No routine monitoring exists, though anti-Xa levels (for FXa inhibitors) or diluted thrombin time (for dabigatran) may be used in specific clinical contexts.
## Clinical Pearls
* **Reversal Agents:** Idarucizumab reverses dabigatran; andexanet alfa reverses apixaban and rivaroxaban.
* **Perioperative Management:** Hold doses 24–72 hours prior to elective procedures depending on bleeding risk and renal function.
* **Renal Function:** Always calculate CrCl personally; electronic health record values may occasionally utilize different formulas (e.g., eGFR calculation instead of Gault).
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**Educational Disclaimer:** This information is for educational purposes only. Direct oral anticoagulants are high-alert medications. Always verify current prescribing information, institutional protocols, and patient-specific factors (e.g., renal function, weight, concomitant meds) via official drug monographs or clinical pharmacy resources before prescribing or administering.
