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# Direct Oral Anticoagulants (DOACs)
## Overview
DOACs include Factor Xa inhibitors (apixaban, rivaroxaban, edoxaban) and direct thrombin inhibitors (dabigatran). Unlike warfarin, they have predictable pharmacokinetics, fewer food-drug interactions, and generally do not require routine coagulation monitoring.
## Primary Indications
* Non-valvular atrial fibrillation (stroke/systemic embolism prophylaxis).
* Treatment and secondary prevention 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. DVT/PE: 10 mg PO BID x 7 days, then 5 mg PO BID.
* **Rivaroxaban:** AFib: 20 mg PO daily with evening meal. DVT/PE: 15 mg PO BID x 21 days, then 20 mg PO daily.
* **Dabigatran:** AFib: 150 mg PO BID. DVT/PE (post-parenteral): 150 mg PO BID.
* **Edoxaban:** AFib: 60 mg PO daily. DVT/PE (post-parenteral): 60 mg PO daily.
## Pediatric Dosing
Dosing is weight/age-based and highly complex. Pediatric anticoagulation protocols vary significantly by institution and underlying condition (e.g., thrombophilia vs. congenital heart disease). Use specialized pediatric nomograms or institutional protocols (VTE guidelines). Pediatric anticoagulation should only be managed by experienced teams.
## Dose Adjustments
* **Renal Impairment:** Critical for all DOACs; primary route of clearance. Requires serum creatinine calculated via Cockcroft-Gault.
* *Example:* Apixaban dose reduction (2.5 mg BID) if ≥2 of the following: Age ≥80, Weight ≤60 kg, or SCr ≥1.5 mg/dL.
* **Hepatic Impairment:** Avoid in moderate-to-severe hepatic impairment (Child-Pugh B or C). Reduce/avoid based on specific drug labeling.
## Contraindications
* Active pathological bleeding.
* Mechanical prosthetic heart valves (Dabigatran is strictly contraindicated; others are generally avoided).
* Moderate-to-severe hepatic impairment.
* Concomitant use of strong dual P-gp and CYP3A4 inhibitors (e.g., ketoconazole, ritonavir).
## Adverse Effects
* Major bleeding (gastrointestinal, intracranial).
* Minor bleeding (epistaxis, gingival, bruising).
* Dyspepsia/gastritis (Dabigatran specifically).
* Anemia.
## Key Drug Interactions
* **P-gp and CYP3A4 inhibitors/inducers:** Significant impact on plasma concentrations; consult a checker for specific combinations.
* **Antiplatelet agents/NSAIDs/SSRIs:** Increased bleeding risk.
* **St. John’s Wort:** Potent inducer; reduces efficacy.
## Monitoring
* **Renal function (baseline and periodic):** Essential for dose adjustment.
* **Complete Blood Count (CBC):** To assess for occult blood loss (hemoglobin/hematocrit).
* **Clinical assessment:** Monitor for signs of bleeding, thrombosis, or adherence.
* *Note:* Routine monitoring of PT/INR or aPTT is imprecise and generally not recommended for assessing therapeutic efficacy.
## Clinical Pearls
* **Reversal:** Idarucizumab is the specific reversal agent for dabigatran. Andexanet alfa is used for apixaban and rivaroxaban.
* **Adherence:** DOACs have short half-lives; missed doses significantly increase the risk of thrombotic events.
* **Transitioning:** Utilize institutional bridge-over protocols when transitioning from warfarin to a DOAC (based on INR) or vice versa.
* **Procedural management:** Withhold 24–72 hours prior to elective surgery based on bleeding risk and renal function.
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*Disclaimer: This information is for educational purposes only. Clinical protocols vary; always verify specific dosing, safety information, and contraindications by consulting current FDA-approved labeling (Package Inserts), professional guidelines (e.g., ASH, ACC, CHEST), and internal institutional policies before prescribing.*
