dabigatran (da-bi-gat-ran) Pradaxa

 Indications

To reduce the risk of stroke/systemic embolization associated

with nonvalvular atrial fibrillation. Treatment

of deep vein thrombosis or pulmonary embolism in patients

who have been treated with parenteral anticoagulant

for 5–10 days. To reduce the risk of recurrence of

deep vein thrombosis or pulmonary embolism in patients

who have been previously treated. Prevention of

deep vein thrombosis and pulmonary embolism following

hip replacement surgery.

Action

Acts as a direct inhibitor of thrombin. Therapeutic

Effects: Lowered risk of thrombotic sequelae (stroke

and systemic embolization) of nonvalvular atrial fibrillation.

Pharmacokinetics

Absorption: 3–7% absorbed following oral administration.

Distribution: Unknown.

Metabolism and Excretion: Of the amount absorbed,

mostly excreted by kidneys (80%); 86% of ingested

dose is eliminated in feces due to poor bioavailability.

Half-life: 12–17 hr.

TIME/ACTION PROFILE (effects on

coagulation)

ROUTE ONSET PEAK DURATION

PO within hours unknown 2 days†

†Following discontinuation, 3–5 days in renal impairment.

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Active pathological

bleeding; Concurrent use of P-glycoprotein (Pgp)

inducers; Prosthetic heart valves (mechanical or

bioprosthetic).

Use Cautiously in: Neuroaxial spinal anesthesia or

spinal puncture, especially if concurrent with an indwelling

epidural catheter, drugs affecting hemostasis,

history of traumatic/repeated spinal puncture or spinal

deformity (qrisk of spinal hematoma); Concurrent

medications/pre-existing conditions thatqbleedingrisk

(other anticoagulants, antiplatelet agents, fibrinolytics,

heparins, chronic NSAID use, labor and delivery);

Renal impairment; Surgical procedures (discontinue

1–2 days prior if CCr 50 mL/min or 3–4 days prior if

CCr 50 mL/min; Geri:qrisk of bleeding; Lactation:

Use cautiously during breast feeding; Pedi: Safety and

effectiveness not established.

Adverse Reactions/Side Effects

GI: abdominal pain, diarrhea, dyspepsia, gastritis,

esophageal ulceration, nausea. Hemat: BLEEDING,

thrombocytopenia. Misc: ANGIOEDEMA, hypersensitivity

reactions including ANAPHYLAXIS.

Interactions

Drug-Drug: Concurrent use of other anticoagulants,

antiplatelet agents, fibrinolytics, heparins,

prasugrel, clopidogrel, or chronic use of NSAIDsq

risk of bleeding. Concurrent use of P-gp inducers including

rifampinplevels and effectiveness; avoid concurrent

use. P-gp inhibitors, including dronedarone,

ketoconazole (systemic), verapamil,

quinidine, and ticagrelor mayqlevels and the risk of

bleeding; concomitant use should be avoided in patients

with CCr 15–30 mL/min.

Route/Dosage

Reduction in Risk of Stroke/Systemic Embolism

in Nonvalvular Atrial Fibrillation

PO (Adults): 150 mg twice daily.

Renal Impairment

PO (Adults): CCr 30–50 mL/min and taking dronedarone

or systemic ketoconazole—75 mg twice

daily; CCr 30 mL/min and taking P-gp inhibitor—

Avoid concomitant use; CCr 15–30 mL/min—75 mg

twice daily; CCr 15 mL/min or on dialysis—Not

recommended.

Treatment of and Reduction in Risk of Recurrence

of Deep Vein Thrombosis or Pulmonary

Embolism

PO (Adults): 150 mg twice daily.

Renal Impairment

PO (Adults): CCr 50 mL/min and taking P-gp inhibitor—

Avoid concomitant use; CCr 30 mL/min or

on dialysis—Not recommended.

Prevention of Deep Vein Thrombosis and

Pulmonary Embolism Following Hip Replacement

Surgery

PO (Adults): 110 mg taken 1–4 hr after surgery and

once hemostasis achieved, then 220 mg once daily for

28–35 days; if unable to start on day of surgery, once

hemostasis achieved, start with 220 mg once daily.

Renal Impairment

PO (Adults): CCr 30 mL/min or on dialysis—Not

recommended; CCr 50 mL/min and taking P-gp inhibitor—

Avoid concomitant use.

Availability

Capsules: 75 mg, 110 mg, 150 mg.