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# Direct Oral Anticoagulants (DOACs)
## Overview
DOACs are potent, target-specific anticoagulants. Dabigatran is a direct thrombin inhibitor (Factor IIa); Rivaroxaban, Apixaban, and Edoxaban are direct Factor Xa inhibitors. Unlike warfarin, they have predictable pharmacokinetics, fewer food/drug interactions, and no routine requirement for coagulogram monitoring.
## Primary Indications
* Non-valvular atrial fibrillation (stroke prophylaxis).
* Treatment and secondary prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE).
* Prophylaxis post-orthopedic surgery (selected agents).
## Adult Dosing
* **Apixaban (Eliquis):** AFib: 5 mg BID (reduce to 2.5 mg BID if ≥2 of: age ≥80, weight ≤60 kg, or Scr ≥1.5 mg/dL). VTE Treatment: 10 mg BID x 7 days, then 5 mg BID.
* **Rivaroxaban (Xarelto):** AFib: 20 mg daily with dinner. VTE Treatment: 15 mg BID x 21 days, then 20 mg daily. Max dose: 20 mg/day for AFib.
* **Dabigatran (Pradaxa):** AFib: 150 mg BID. VTE Treatment: 150 mg BID after 5-10 days of parenteral anticoagulation.
* **Edoxaban (Savaysa):** AFib: 60 mg daily (do not use if CrCl >95 mL/min). VTE Treatment: 60 mg daily after 5-10 days of parenteral anticoagulation.
## Pediatric Dosing
Dosing is highly weight-based and restricted to specific formulations (or manipulated crushed dosing). **Refer to institutional pediatric hematology guidelines or current clinical trials (e.g., EINSTEIN-Jr/RE-扉EDUCE) before prescribing.** Off-label use requires expert oversight; doses are typically extrapolated from body surface area or weight-based nomograms.
## Dose Adjustments
* **Renal Impairment:** Mandatory. All DOACs require dose reduction or avoidance in severe renal impairment (CrCl <30 mL/min; Dabigatran <15 mL/min or 30 mL/min depending on clinical setting).
* **Hepatic Impairment:** Avoid or exercise extreme caution in Child-Pugh B or C.
## Contraindications
* Active pathological bleeding.
* Mechanical prosthetic heart valves (significant morbidity/mortality risk).
* Moderate-to-severe mitral stenosis.
* Hypersensitivity.
* High-risk pregnancy (Category: Avoid/Caution).
## Adverse Effects
* Major and minor hemorrhage (GI, intracranial).
* Dyspepsia (most common with Dabigatran due to tartaric acid core).
* Anemia.
## Key Drug Interactions
* **P-gp and CYP3A4 inhibitors/inducers:** Combined P-gp/strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) significantly increase DOAC exposure.
* **P-gp/CYP3A4 inducers:** (e.g., rifampin, carbamazepine, St. John's wort) decrease efficacy.
* **Antiplatelets/NSAIDs:** Increase bleeding risk synergistically.
## Monitoring
* Baseline: CBC (baseline anemia risk), Scr/CrCl (Cockcroft-Gault), LFTs.
* Routine: Annual renal/hepatic function check.
* No routine INR/PT/aPTT monitoring; specific coagulation assays (e.g., anti-Xa levels for Xa inhibitors) exist but are not validated for routine dose titration.
## Clinical Pearls
* **Reversal:** Idarucizumab is specific to Dabigatran; Andexanet alfa is the reversal agent for Apixaban/Rivaroxaban (if criteria are met).
* **Glomerular Hyperfiltration:** Edoxaban should not be used in AFib patients with CrCl >95 mL/min due to increased risk of ischemic stroke despite therapeutic dosing.
* **Compliance:** Short half-lives make missed doses high-risk for thromboembolism.
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*Disclaimer: This information is for educational purposes. Always verify current prescribing information, institutional protocols, and patient-specific contraindications via official FDA-approved labeling or clinical decision support tools before prescribing.*
