dabigatran


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dabigatran

(da-bye-gat-ran) ,

Pradaxa

(trade name)

Classification

Therapeutic: anticoagulants
Pharmacologic: thrombin inhibitors
Pregnancy Category: C

Indications

To reduce the risk of stroke/systemic embolization associated with nonvalvular atrial fibrillation.

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)

ROUTEONSETPEAKDURATION
POwithin hoursunknown2 days†
†Following discontinuation, 3–5 days in renal impairment.

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Active pathological bleeding;Concurrent use of P-glycoprotein (P-gp) inducers;Prosthetic heart valves (mechanical or bioprosthetic)
Use Cautiously in: Concurrent medications/pre-existing conditions that ↑ bleeding risk (other anticoagulants, antiplatelet agents, antifibrinolytics, heparins, chronic NSAID use, labor and delivery);Renal impairmentSurgical procedures (discontinue 1–2 days prior if CCr ≥50 mL/min or 3–4 days prior if CCr <50 mL/min; Geriatric: ↑ risk of bleeding; Lactation: Use cautiously during breast feeding; Pediatric: Safety and effectiveness not established.

Adverse Reactions/Side Effects

Gastrointestinal

  • abdominal pain (most frequent)
  • diarrhea (most frequent)
  • dyspepsia (most frequent)
  • gastritis (most frequent)
  • nausea

Hematologic

  • bleeding
  • thrombocytopenia

Miscellaneous

  • angioedema (life-threatening)
  • hypersensitivity reactions including anaphylaxis (life-threatening)

Interactions

Drug-Drug interaction

Concurrent use of other anticoagulants, antiplatelet agents, antifibrinolytics, heparins, prasugrel, clopidogrel, or chronic use of NSAIDs ↑ risk of bleeding.Concurrent use of P-gp inducers including rifampin ↓ levels and effectiveness; avoid concurrent use.P-gp inhibitors, including dronedarone and ketoconazole (systemic), may ↑ levels and the risk of bleeding; concomitant use should be avoided in patients with CCr 15–30 mL/min.

Route/Dosage

Oral (Adults) 150 mg twice daily.

Renal Impairment

Oral (Adults) CCr 30–50 mL/min and taking dronedarone or systemic ketoconazole—75 mg twice daily; CCr 15–30 mL/min—75 mg twice daily; CCr 15–30 mL/min and taking P-gp inhibitor—Avoid concomitant use; CCr <15 mL/min—Not recommended.

Availability

Capsules: 75 mg, 110 mg, 150 mg

Nursing implications

Nursing assessment

  • Assess for symptoms of stroke or peripheral vascular disease periodically during therapy.
  • Assess for symptoms of bleeding and blood loss; may be fatal.
  • Lab Test Considerations: Use aPTT or ECT, not INR, to assess anticoagulant activity, if needed.
    • Monitor renal function prior to and periodically during therapy. Patients with renal impairment may require dose reduction or discontinuation.

Potential Nursing Diagnoses

Activity intolerance

Implementation

  • When converting from warfarin, discontinue warfarin and start dabigatran when INR is <2.0.
  • When converting from dabigatran to warfarin, adjust starting time based on creatinine clearance. For CCr >50 mL/min, start warfarin 3 days before discontinuing dabigatran. For CCr 31–50 mL/min, start warfarin 2 days before discontinuing dabigatran. For CCr 15–30 mL/min, start warfarin 1 day before discontinuing dabigatran. For CCr <15 mL/min, no recommendations can be made. INR will better reflect warfarin's effect after dabigatran has been stopped for at least 2 days.
  • When converting from parenteral anticoagulants, start dabigatran up to 2 hr before next dose of parenteral drug is due or at time of discontinuation of parenteral therapy.
  • When converting to dabigatran from parenteral anticoagulants, wait 12 hrs (CCr ≥30 mL/min) or 24 hr (CCr <30 mL/min) after last dose of dabigatran before initiating parenteral anticoagulant therapy.
  • For surgery, discontinue dabigatran 1–2 days (CrCL ≥50 mL/min) or 3–5 days (CCr <50 mL/min) before invasive or surgical procedures; consider longer times for major surgery, spinal puncture, or placement of a spinal or epidural catheter. If surgery cannot be delayed, bleeding risk is ↑. Assess bleeding risk with ecarin clotting time (ECT) or a PTT if ECT is not available.
  • Oral: Administer twice daily without regard to food. Swallow capsule whole; do not open, crush, or chew; may result in increased exposure.
    • If dabigatran is discontinued, consider starting another anticoagulant; discontinuation of dabigatran increases risk of thrombotic events.

Patient/Family Teaching

  • Instruct patient to take dabigatran as directed. Take missed doses as soon as remembered within 6 hr. If <6 hr until next dose, skip dose and take next dose when scheduled; do not double doses. Do not discontinue without consulting health care professional. If temporarily discontinued, restart as soon as possible. Store dabigatran at room temperature. After opening bottle, use within 4 mo; discard unused dabigatran after 4 mo.
  • Inform patient that they may bleed more easily or longer than usual. Advise patient to notify health care professional immediately if signs of bleeding (unusual bruising; pink or brown urine; red or black, tarry stools; coughing up blood; vomiting blood; pain or swelling in a joint; headache; dizziness; weakness; recurring nose bleeds; unusual bleeding from gums; heavier than normal menstrual bleeding; dyspepsia; abdominal pain; epigastric pain) occur..
  • Advise patient to notify health care professional of medication regimen prior to treatment or surgery.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
  • Advise female patient to notify health care professional if pregnancy is planned or suspected or if breast feeding.

Evaluation/Desired Outcomes

  • Reduction in the risk of stroke and systemic embolism.
References in periodicals archive ?
Based on the mean event rate calculated in the result, warfarin had the highest risk of stroke occurrence compared to dabigatran 110 mg and 150 mg.
Germany-based Boehringer Ingelheim, has received approval from the European Commission for its Praxbind (idarucizumab) for the specific reversal of Pradaxa (dabigatran etexilate), it was reported on Friday.
Hence, the race among pharmaceutical manufacturers to find such antidotes with few drug interactions, rapid reversal potential, and minimal adverse effects has accelerated during the past 18 months, and especially after new reports of increased bleeding risks with dabigatran (Pradaxa[R]) highlighted in a series of articles in the British Medical Journal over the last six months (Charlton & Redberg, 2014; Cohen, 2014a, 2014b; McCarthy, 2014; Moore, Cohen, & Mattison, 2014).
At present, there are 3 NOACs available in the United States: dabigatran etexilate (dabigatran; Pradaxa, Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut); rivaroxaban, (Xarelto, Janssen Pharmaceuticals, Titusville, New Jersey); and apixaban (Eliquis, Bristol-Myers Squibb, Princeton, New Jersey).
If we could develop a drug that had the anticoagulant properties of Warfarin but did not cause bleeding, had fewer interactions with other drugs, was not affected by diet, and could be given as a fixed dose that would be highly beneficial for patients." He then explained that four effective Warfarin alternatives -- Dabigatran, Rivaroxaban, Apixaban, Edoxaban -- all require differential dosage depending on a number of variables.
While Apixaban and Edoxaban cause slightly less bleeding than Warfarin, Dabigatran and Rivaroxaban cause about the same amount.
PATIENTS RECEIVING ORAL anticoagulant treatment had the lowest risk of gastrointestinal bleeding when taking apixaban, compared with rivaroxaban, dabigatran, and warfarin, according to a recent study.
Idarucizumab, an agent to reverse the anticoagulant effects of dabigatran, was approved in 2015 for patients who develop serious bleeding or require urgent surgical intervention.
CHICAGO--Apixaban outperformed two other direct-acting oral anticoagulants, dabigatran and rivaroxaban, by preventing more thrombotic events and not causing as many major bleeds in patients with atrial fibrillation who were at least 80 years old.
After the adjustment of antihypertensive therapy, initiation of antibiotics for cystitis and parenteral anticoagulant in the context of AF, the progress was favorable and the patient was discharged on treatment including NOAC (Dabigatran 150 mg twice daily).
Drugs targeting venous or stasis-induced thrombi include the traditional anticoagulants (heparin, low-molecular-weight (LMW) heparins and fondaparinux), the VKAs (warfarin), and more recently the novel or direct-acting oral anticoagulants (DOACs) (dabigatran, rivaroxaban and apixaban).