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# Direct Oral Anticoagulants (DOACs)
## Overview
DOACs are target-specific anticoagulants consisting of direct thrombin inhibitors (dabigatran) and Factor Xa inhibitors (apixaban, rivaroxaban, edoxaban). They are preferred over warfarin for non-valvular atrial fibrillation (NVAF) and venous thromboembolism (VTE) due to predictable pharmacokinetics, lack of routine INR monitoring, and fewer dietary interactions.
## Primary Indications
* Stroke prophylaxis in NVAF.
* Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE).
* Prevention of recurrent DVT/PE.
* Thromboprophylaxis following hip or knee replacement (rivaroxaban, apixaban, dabigatran).
## Adult Dosing
* **Apixaban (Eliquis):**
* NVAF: 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):**
* NVAF: 20 mg daily with the evening meal.
* VTE treatment: 15 mg BID x 21 days, then 20 mg daily.
* **Dabigatran (Pradaxa):**
* NVAF/VTE treatment: 150 mg BID. (110 mg BID if age >80 or high bleed risk).
* **Edoxaban (Savaysa):**
* NVAF: 60 mg daily (Do not use if CrCl >95 mL/min due to reduced efficacy).
## Pediatric Dosing
Pediatric dosing is highly protocol-dependent and weight-based.
* **Dabigatran:** Approved for children 3 months to <18 years (capsules >8 years). Dosing is based on weight-based nomograms.
* **Rivaroxaban:** Approved for children birth to <18 years (suspension/tablets). Dosing is strictly weight-based.
* *Note: Consult institution-specific pediatric hematology/oncology guidelines or specialized dosing calculators (e.g., Lexicomp/NeoFax) before prescribing.*
## Dose Adjustments
* **Renal Impairment:** Crucial for all DOACs.
* Apixaban: No specific adjustment until CrCl <15 mL/min (use with caution).
* Rivaroxaban/Edoxaban/Dabigatran: Require significant dosage reductions or avoidance based on CrCl (refer to specific package inserts).
* **Hepatic Impairment:** Avoid in Child-Pugh Class B or C; verify labeling per agent.
## Contraindications
* Active pathological bleeding.
* Mechanical heart valves (dabigatran is strictly contraindicated).
* Moderate to severe hepatic impairment (variable by agent).
* Severe renal impairment (CrCl <15–30 mL/min depending on agent).
* Concurrent use of strong dual P-gp and CYP3A4 inhibitors/inducers.
## Adverse Effects
* Major and clinically relevant non-major bleeding.
* Gastrointestinal distress (dabigatran is associated with dyspepsia).
* Anemia.
## Key Drug Interactions
* **P-gp and CYP3A4 Inhibitors (e.g., ketoconazole, ritonavir, clarithromycin):** May increase DOAC levels and bleed risk.
* **P-gp and CYP3A4 Inducers (e.g., rifampin, phenytoin, carbamazepine, St. John’s Wort):** May significantly decrease DOAC efficacy.
* **Antiplatelets/NSAIDs:** Increase combined risk of bleeding.
## Monitoring
* **Baseline:** CBC (baseline/periodic), CrCl (Cockcroft-Gault), LFTs.
* **Routine:** Periodic assessment of renal function is mandatory (at least annually; more frequently in elderly or CKD).
* **Emergencies:** No routine coagulation test (PT/INR) is reliable. Use Ecarin Clotting Time or Thrombin Time for dabigatran; anti-Xa activity assays for Xa inhibitors.
## Clinical Pearls
* **Dabigatran:** Must be stored in the original bottle with the desiccant cap; it is sensitive to moisture. Never crush/open capsules.
* **Non-valvular AF:** Ensure "non-valvular" qualification; DOACs are not indicated for mitral stenosis or mechanical prosthetic valves.
* **Adherence:** DOACs have short half-lives; missed doses lead to rapid loss of anticoagulant effect.
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**Educational Disclaimer:** This information is for educational purposes only. Always verify dosing, contraindications, and drug interactions using current prescribing information (package inserts) and local institutional protocols before clinical use.
