Dabigatran Etexilate

Class and Category

Pharmacologic Class: Direct thrombin inhibitor

Therapeutic Class: Anti-coagulant

Indications and Dosages

To reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation

CAPSULES

Adults: 

Adults with creatinine clearance greater than 30 ml/min.: 150 mg twice daily.

Adults with creatinine clearance between 15 and 30 ml/min.: 75 mg twice daily.

Dosage Adjustment:

For patients with a creatinine level between 30 and 50 ml/min and taking dronedarone or systemic ketoconazole concomitantly, the dosage decreased to 75 mg twice daily.

To treat deep vein thrombosis and pulmonary emboliin patients who have been treated with a parenteral anticoagulant for 5 to 10 days; to reduce risk of recurrence of deep vein thrombosis and pulmonary emboli in patients who have been previously treated

CAPSULES

Adults: 

Adults with creatinine clearance greater than 30 ml/min.: 150 mg twice daily.

To prevent deep vein thrombosis and pulmonary embolism following a hip replacement 

CAPSULES

Adults: 

Adults with creatinine clearance greater than 30 ml/min.: 150 mg twice daily.

110 mg 1 to 4 hr after surgery and after hemostasis has been achieved on the first day, then 220 mg once daily for 28 to 35 days.

Dosage Adjustment:

For patients with creatinine clearance less than 50 ml/min and prescribed a P-gp inhibitor, dabigatran was discontinued.

Mechanism of Action

Directly inhibits thrombin from converting fibrinogen into fibrin during the coagulation cascade. Inhibition of this activity prevents the development of a blood clot.

Contraindications

Active pathologic bleeding, hypersensitivity to dabigatran or its components, presence of mechanical prosthetic heart valve.

Interactions

DRUGS

P-gp inducers such as rifampin: Decreased exposure to dabigatran

P-gp inhibitors such as dronedarone, ketoconazole: Increased exposure to dabigatran in patients with renal impairment

Adverse Reactions

CNS: Intracranial or intraspinal hemorrhage

CV: Pericardial bleeding

EENT: Intraocular bleeding

GI: Diarrhea, dyspepsia, esophageal ulcer, gastritis-like symptoms, gastrointestinal hemorrhage, nausea, retroperitoneal bleeding, upper abdominal pain

HEME: Bleeding (serious), thrombocytopenia

MS: Intra-articular bleeding, intramuscular bleeding with compartment syndrome

SKIN: Pruritus, rash, urticaria

Other: Anaphylactic reaction or shock, angioedema

Childbearing Considerations

PREGNANCY

• It is not known if the drug causes fetal harm although the use of anticoagulants such as dabigatran may increase the risk of bleeding in the fetus.
• Drugs should be used with caution during pregnancy only if the benefit to the mother outweighs the potential risk to the fetus.

LABOR & DELIVERY

• The drug may cause maternal bleeding and hemorrhage if given during labor and delivery.
• Know that the drug should be temporarily withheld or a shorter-acting anticoagulant substituted as delivery approaches or if neuraxial anesthesia is expected to be used during delivery.

LACTATION

• It is not known if drug is present in breast milk.
• Breastfeeding is not recommended during drug therapy.

Nursing Considerations

• Be aware that dabigatran should not be used in patients with triple-positive antiphospholipid syndrome because of the increased risk for recurrent thrombosis.
• Assess renal function, as ordered, prior to beginning dabigatran therapy because dose is based on the patient’s creatinine level. Continue to monitor the patient’s serum creatinine level throughout therapy, as ordered, and expect frequency of serum creatinine tests to increase if a patient develops a condition that affects renal function because a dosing adjustment may be required. Know that the drug should be discontinued if the patient develops acute renal failure.
• Be aware that patients converting from warfarin to dabigatran therapy should begin dabigatran therapy when their international normalized ratio (INR) is below 2.0.
• Expect patients converting from dabigatran to warfarin therapy to do so based on their creatinine clearance level. For patients who have a creatinine clearance level greater than 50 ml/min, expect warfarin to be started 3 days before dabigatran is discontinued. For patients who have a creatinine clearance level of 31 to 50 ml/min, expect warfarin to be started 2 days before dabigatran is discontinued. For patients who have a creatinine clearance level of 15 to 30 ml/min, expect warfarin to be started 1 day before dabigatran is discontinued. No recommendations are available for patients who have a creatinine clearance level of less than 15 ml/min.
• Be aware that degree of anticoagulation does not need to be assessed by routine laboratory testing with dabigatran use. However, when necessary, expect the prescriber to use activated partial thromboplastin time (aPTT) or ecarin clotting time (ECT), and not INR, to assess for anticoagulant activity for the patient receiving dabigatran therapy.
• Know that dabigatran can elevate the patient’s INR. Therefore, when patients are transitioned, dabigatran must be stopped for at least 2 days before the most accurate effects of warfarin can be known.
• Begin dabigatran therapy, as ordered, for a patient currently receiving a parenteral anticoagulant, such as heparin, within 2 hours before the next dose of the parenteral drug was to have been administered. If the parenteral anticoagulant being used is continuous in nature, expect to begin dabigatran therapy upon discontinuation of the continuously administered parenteral anticoagulant.

• Expect to begin treatment with a parenteral anticoagulant, if ordered, 12 hours after the patient’s final dabigatran dose if the patient has a creatinine clearance of 30 ml/min or greater, and 24 hours after the patient’s final dabigatran dose if the patient’s creatinine clearance is less than 30 ml/min.
• Know that dabigatran therapy should be discontinued, if possible, 1 to 2 days before invasive or surgical procedures for patients with a creatinine clearance of 50 ml/min or more, and 3 to 5 days for patients whose creatinine clearance is less than 50 ml/min because of the increased risk for bleeding. Longer times may be required for patients undergoing major surgery, spinal puncture, or placement of a spinal or epidural catheter or port, in whom complete hemostasis is required. If surgery cannot be postponed, monitor patient closely for bleeding and assess bleeding risk with the ECT. If an ECT measurement is not possible, know that the aPTT can provide an approximation of dabigatran’s anticoagulant activity.

WARNING: Monitor patient closely for bleeding because dabigatran increases risk for bleeding, which can become severe. Bleeding risk increases in patients taking concurrent antiplatelet drugs, fibrinolytic therapy, heparin, or with chronic use of NSAIDs. It also increases during labor and delivery. Monitor patient very closely. Promptly report any signs or symptoms of bleeding such as a drop in hemoglobin and/or hematocrit or the development of hypotension or overt bleeding. Expect to discontinue drug if active bleeding  occurs and is persistent or serious. Know that protamine sulfate and vitamin K will not affect the anticoagulant activity of dabigatran. Instead, the prescriber may prescribe platelet concentrates if thrombocytopenia is present or the patient has been exposed to long-acting antiplatelet drugs. If bleeding is life-threatening or uncontrolled or emergency surgery or urgent procedures are necessary, expect to administer idarucizumab to reverse the anticoagulant effect of dabigatran.

• Know that premature discontinuation of dabigatran increases the risk of thrombotic events. Be aware that patients receiving spinal/epidural anesthesia or a spinal puncture are at risk of developing an epidural or spinal hematoma, which can result in long-term or permanent paralysis. Monitor patient frequently for signs or symptoms of neurologic impairment. Notify prescriber immediately if patient complains of bladder or bowel dysfunction, midline back pain, or numbness, tingling, or weakness in the lower extremities.
• Assess patient closely for stroke if dabigatran therapy must be discontinued temporarily because of an active bleed, elective surgery, or an invasive procedure. Also, be aware that premature discontinuation of the drug increases risk of thrombotic events. Know that therapy should be restarted as soon as possible. If the drug must be discontinued for reasons other than pathological bleeding, expect patient to receive coverage with another anticoagulant to decrease the risk of thrombotic events, such as stroke.

WARNING: Be on the alert for an epidural or spinal hematoma formation in patients receiving dabigatran and neuraxial anesthesia or undergoing spinal puncture. This hematoma may result in long-term or permanent paralysis. Assess patient frequently for signs and symptoms of neurological impairment. If present, notify prescriber immediately as urgent treatment is necessary.

PATIENT TEACHING

• Tell the patient to take dabigatran exactly as prescribed.
• Instruct the patient to swallow the capsule whole without breaking, chewing, or emptying the contents of the capsule prior to ingestion.
• Tell the patient that if she misses a dose, she should take it as soon as she remembers on the same day she missed the dose unless it is within 6 hours of the next dose. She should never double a dose to make up for a missed dose.
• Instruct patient to keep bottle tightly closed when not in use and store in the original package to protect from moisture. Have the patient date the bottle when opened and tell her to discard any remaining drug if not used within 4 months of initially opening the bottle.
• Urge the patient to take precautions against bleeding, such as using an electric shaver and a soft-bristled toothbrush.
• Caution patient to avoid activities that could cause traumatic injury and bleeding.
• Urge the patient to notify the prescriber immediately about unusual bleeding and any unexplained symptoms, such as abnormal vaginal bleeding; dizziness; easy bruising; gum bleeding; red or dark brown urine; stools that are black or tarry; vomiting blood or vomit that looks like coffee grounds; and weakness.
• Caution patient not to stop taking dabigatran abruptly.
• Urge the patient to carry medical identification that reveals she is taking dabigatran.
• Tell the patient to inform all healthcare providers that she is taking dabigatran and not to take any medication, including OTC drugs, without first consulting the prescriber.
• Warn mothers not to breastfeed while taking dabigatran because of the increased risk of bleeding in the infant.