Pradaxa | Pharmacology Mentor

Generic Name

Pradaxa (dabigatran etexilate)

Mechanism

Direct thrombin inhibition: Dabigatran etexilate is a prodrug converted by esterases to dabigatran, which binds the catalytic site of thrombin (factor IIa) with high affinity.
Prevents fibrin formation: By blocking thrombin, it curtails thrombin‑mediated conversion of fibrinogen to fibrin and platelet activation.
Fast onset: Peak plasma concentration in ~2–3 h, giving rapid anticoagulation.

Pharmacokinetics

Parameter	Detail
Absorption	Oral, with 30–35% bioavailability; roughly 1‑2 h to peak.
Metabolism	Predominantly unchanged in plasma; minor carboxylesterase metabolism.
Elimination	Renal excretion (~80% unchanged). Half‑life ≈ 12 h (shorter in dialysis).
Inhibitors/Inducers	CYP?, mainly unaffected; however, co‑administration with strong CYP3A4 inhibitors (e.g., ketoconazole) may modestly increase levels.
Food effect	No significant impact when taken with or without food, but recommended with food to enhance absorption.

Indications

Stroke prophylaxis in patients with non‑valvular atrial fibrillation (NVAF).
Treatment of deep‑vein thrombosis (DVT) and pulmonary embolism (PE).
Secondary prevention of VTE after initial therapy.
Extended prophylaxis post‑orthopedic surgery (hip or knee replacement).

Contraindications

Absolute contraindications: Hypersensitivity to dabigatran, severe renal impairment (CrCl < 15 mL/min), active bleeding, or concomitant use of strong anticoagulants (warfarin, LMWH).
Relative warnings: Significant hepatic impairment, uncontrolled hypertension, pregnancy (not approved), and if patient is on dual antiplatelet therapy with high bleeding risk.

Dosing

Indication	Dose (orog)	Frequency	Renal adjustment	Notes
NVAF	150 mg BID	12 h	CrCl 30–49 mL/min: 75 mg BID; <30 mL/min: not recommended	First dose must be 300 mg (150 mg BID) for 3 days; then 150 mg BID.
DVT/PE	150 mg BID	12 h	CrCl 30–49 mL/min: 75 mg BID; <30 mL/min: not recommended	5‑day loading phase at 150 mg Q12h for patients with CrCl ≥ 50 mL/min; otherwise 75 mg BID.
Orthopedic prophylaxis	150 mg BID	12 h	CrCl 30–49 mL/min: 75 mg BID; <30 mL/min: not recommended	Administer 4 weeks after surgery, starting day 4–7 post‑op.

• Take with ≥ 240 mL of water and a meal to maintain bioavailability.
• Avoid high‑pressure gastric pH modifiers that may alter absorption.

Adverse Effects

Common: Dyspepsia, epigastric pain, nausea, diarrhea, urinary tract pain, mild anemia.
Serious: Major bleeding (intracranial, GI), moderate bleeding, renal dysfunction, hypersensitivity.
Rare: Hepatotoxicity, hypersensitivity rash, acute kidney injury.

Monitoring

Renal function: eGFR/CrCl every 4–6 months; more frequent if CrCl < 50 mL/min.
Bleeding signs: bruising, hematuria, hematochezia.
Lab tests: Routine coagulation labs (PT/INR) not reliable; use activated partial thromboplastin time (aPTT) or dilute thrombin time (DTT) for intense monitoring if necessary.
Weight/BP: Monitor for hypertension.

Clinical Pearls

1. “Dabigatran on the go” – Because Danio (insulin‑like growth factor) is only available as a tablet, paediatric or oropharyngeal patients may use a mouth‑to‑gut feeding tube (if warranted by the case‑specific risk‑benefit assessment).

2. Renal‑safe switch – In patients with CrCl 30–49 mL/min, simply downsizing the dose to 75 mg BID preserves therapeutic effect while mitigating renal elimination risk.

3. No reversal agent, yet – idarucizumab (Praxbind) is the specific antidote for dabigatran; read the emergency protocol if massive hemorrhage is suspected.

4. Drug‑drug interplay – Avoid NSAIDs or other GI‑irritants; they can accentuate dyspepsia or increase GI bleeding risk.

5. Patient education – Emphasize the importance of continuous daily intake; interruption >24 h may reset the anticoagulant effect, especially in patients with low eGFR.

--
• *This drug card is intended for educational purposes only and should not replace clinical judgment or up‑to‑date guidelines.*