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# Direct Oral Anticoagulants (DOACs)
## Overview
DOACs include Direct 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
* Prevention of stroke/systemic embolism in non-valvular atrial fibrillation (NVAF).
* Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE).
* Reduction in risk of recurrence of DVT and PE.
* Prophylaxis of DVT following hip or knee replacement surgery.
## Adult Dosing
* **Apixaban (Eliquis):** NVAF: 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 PO BID for 7 days, then 5 mg PO BID.
* **Rivaroxaban (Xarelto):** NVAF: 20 mg PO daily (with evening meal). DVT/PE treatment: 15 mg PO BID for 21 days, then 20 mg PO daily.
* **Dabigatran (Pradaxa):** NVAF: 150 mg PO BID. (110 mg BID may be considered for select patients/countries). DVT/PE treatment (post-parenteral): 150 mg PO BID.
* **Edoxaban (Savaysa):** NVAF: 60 mg PO daily. Avoid if CrCl >95 mL/min (increased stroke risk). DVT/PE treatment: 60 mg PO daily (post-parenteral).
## Pediatric Dosing
Dosing is highly weight-based and age-dependent. Typically reserved for specialized centers. **Rivoraxaban and Dabigatran** have FDA-approved pediatric formulations for VTE treatment; dosing is calculated per body surface area (BSA) and weight. **Consult institutional protocols and current guidelines (e.g., ISTH, ASH) due to high-risk nature.**
## Dose Adjustments
* **Renal Impairment:** Most DOACs require dose reduction or avoidance based on CrCl (Cockcroft-Gault preferred). Dabigatran is 80% renal-cleared (contraindicated in severe renal failure).
* **Hepatic Impairment:** Avoid in Child-Pugh Class B or C (varies by drug).
## Contraindications
* Active pathological bleeding.
* Mechanical prosthetic heart valves (Dabigatran is explicitly contraindicated; others used with caution/not recommended).
* Severe renal impairment (CrCl <15–30 mL/min depending on agent).
* Moderate-to-severe hepatic impairment (Child-Pugh B/C).
## Adverse Effects
* Major and minor bleeding.
* Gastrointestinal distress (Dabigatran: dyspepsia).
* Anemia.
## Key Drug Interactions
* **Strong Dual P-gp and CYP3A4 inhibitors/inducers:** Co-administration (e.g., ketoconazole, rifampin, phenytoin, carbamazepine, St. John’s Wort) can significantly alter DOAC serum concentrations.
* **Antiplatelets/NSAIDs/SSRIs:** Increase bleeding risk synergistically.
## Monitoring
* Baseline: CBC (baseline/regularly), SCr, LFTs, PT/aPTT (not for routine efficacy, but useful to assess if presence of drug is suspected).
* Compliance: Essential, as DOACs have short half-lives; missed doses increase acute stroke/embolism risk.
* Renal function: At least annually (or more frequently in elderly/renal dysfunction).
## Clinical Pearls
* **Reversal:** Idarucizumab (Praxbind) for Dabigatran; Andexanet alfa (Andexxa) for FXa inhibitors.
* **Surgery:** Usually "hold" 48 hours prior to elective procedures with average bleeding risk (longer if renal impairment or high-risk procedure).
* **Transitioning:** Use "switch calculators" or clinical decision support tools when transitioning from warfarin or parenteral anticoagulants.
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*Disclaimer: This information is for educational purposes for healthcare professionals. Clinical practice guidelines are subject to change; always verify current prescribing information in the package insert or institutional drug formulary before making prescribing decisions.*
