Dabigatran Etexilate for Preventing Stroke and Systemic Embolism

Overview:

Dabigatran etexilate is a customarily advocated oral pill to obviate stroke (brain attack where brain blood flow gets intercepted). Likewise, Dabigatran etexilate could also hold back systemic embolism (an awful condition where the blood clot traverses through the active bloodstream) risks. Dabigatran etexilate could palliate and bring down systemic embolism and stroke encounters in those with apparent risk quotients. The United States (US) Food and Drug Administration (FDA) validated and scrutinized Dabigatran etexilate’s therapeutic application. It gained FDA endorsement as a preventive strategy for systemic embolism and stroke. Dabigatran etexilate acquired its marketing sanction from the US FDA on October 19th, 2010.

Drug Group:

Direct thrombin inhibitor (DTI) drug class board and accommodate Dabigatran etexilate within. Direct thrombin inhibitor, a novel antithrombotic drug class, potentially halts aberrant blood clots from emerging within the vessel. Dabigatran etexilate supersedes and overthrows Warfarin, the customarily advocated blood thinner medication.

Available Doses and Dosage Forms:

• Dosage Forms: Pill form (pellets and capsules).

• Available Dose: 75 milligrams (mg) pill.

• Administration Route: Oral ingestion.

For Patients:

What Is Stroke and Systemic Embolism?

Being a critical organ, the brain could not bear and condone the slightest downfall in blood flow. Any form of interception in the channeling and conveyance of blood to the brain cells can pull off a stroke, otherwise called a brain attack. Oxygen and nutrient deprivation within the brain cells are the prime culprits that could bring forth a stroke. Sometimes, the brain's bloodstream may get intercepted and shut off by blood vessel puncture. Such instances may also instigate brain stroke. Brain stroke could bring out irrevocable harm to the brain. Owing to the degree of brain insult and oxygen deprivation, the outcome of stroke differs. It may prompt permanent incapacity, disablement, or, at times, even abrupt loss of life.

Systemic embolism is another peculiar condition where the aberrantly emerged blood clot channels and course through the bloodstream. These blood clots may then occlude and plug thin blood vessels, delimiting patency in the bloodstream by narrowing the stream. The particulate (blood clot) that impedes and intercepts the blood flow is regarded as an embolus. A heart problem called atrial fibrillation could provoke and instigate systemic embolism. Atrial fibrillation is stamped by unsteady and erratic heartbeats emerging from the atria (the heart’s upper chambers). This unrhythmic beating may deepen one’s propensity to stroke and systemic embolism by favoring clot formation.

How Does Dabigatran Etexilate Work?

Being a direct thrombin inhibitor, Dabigatran etexilate works by holding up the coagulation (blood clotting) process. The fibrinogen (a glycoprotein) gets transmuted into fibrin (proteinaceous insoluble structure) under the thrombin enzyme’s catalytic activity. Thus, formed fibrin molecules interact and collaborate to establish blood clots. Thrombin enzymes, therefore, project a decisive role in buttressing blood clot formation. Dabigatran etexilate intercepts and hampers clot formation owing to its thrombin-inhibitory effect.

What Is the Dosage of Dabigatran Etexilate?

150 milligrams of Dabigatran etexilate is the advocated dose. Dabigatran etexilate has to be employed at a daily frequency of two if and only if the creatinine clearance rate (reflects the kidney’s creatinine extracting efficacy) is beyond 30 milliliters per minute. Owing to one’s creatinine clearance rate, appropriate down regulations in the Dabigatran etexilate dose are instituted to ensure that the kidneys are not weighted down.

How Effective Is Dabigatran Etexilate?

Dabigatran etexilate is a validated direct thrombin inhibitor. Dabigatran holds superior anticoagulant and safety outcomes. It even surpasses the potency offered by Warfarin, which is often the customarily chosen anticoagulant drug. Despite projecting superior therapeutic aspects, Dabigatran etexilate does not draw out alarming side effects. Dabigatran molecules check thrombin activity and thereby intercept and seal blood clotting. Therefore, Dabigatran etexilate therapy is claimed to be a promising standby for Warfarin. Unlike Warfarin, Dabigatran etexilate therapy does not require repeated scrutiny and assessment. Additionally, the foreseeable nature of Dabigatran’s pharmacological specifications further upgraded its safety traits in systemic embolism and stroke.

What Are the Things to Inform the Doctor Before Taking the Drug?

• Dabigatran Allergy: Instances of aberrant and overstated reactivity with Dabigatran. This guides the physician in drug selection.

• Medical History: Health information records comprehending ailments (like bleeding issues, kidney disease, and stomach ulcers), disabilities, replaced heart valves, and cured comorbidities. These health documents serve as blueprints of one’s health status.

• Drug Allergy: Allergic response is when confronted with any medications (pill, injection, or ointment forms).

• Drug History: Records documenting one’s medications. It should cover all medicines, supplements, and even plant-based products.

• Pregnancy: Pregnancy plans and conception status are two key pieces of information the physician should be aware of.

• Lactation: Nursing women must bring it to the physician’s notice. This prevents unintended harm or toxicity issues for the baby as well.

How Is Dabigatran Etexilate Administered?

Dabigatran etexilate ought to be delivered via the mouth. With a tumbler of water, ingest and engulf the pill (capsule form). Fragmenting, powdering, or grinding the pill turns up the Dabigatran exposure, which may surpass the intended Dabigatran exposure range. Adhere to a fixed Dabigatran ingestion time all through the drug course. Dabigatran etexilate can be incorporated with apple juice, mashed banana, or other soft meals when delivered in pellet form. It must be ingested within 30 minutes after incorporation into edibles. Milk products and milk should not be employed for Dabigatran incorporation.

What Are the Side Effects of Dabigatran Etexilate?

Side effects confronted with Dabigatran etexilate include the following:

• Bleeding tendency.

• Stomach upset.

• Abdominal pain.

• Heartburn (bringing up the gut content).

• Nausea (tendency to throw up).

The above-quoted Dabigatran etexilate’s side effects often resolve and settle down. However, Dabigatran may also bring forth certain alarming side effects, which would bring forth health complications:

• Black or bloody stool.

• Bloody vomit.

• Blood-tinged urine.

• Bleedy gums.

• Uncontrollable bleeding from cuts.

• Nosebleeds.

• Skin rash.

• Labored breathing.

• Abnormal periods bleed.

• Headache.

• Chest discomfort.

• Facial puffiness.

• Exhausted feeling.

Dietary Considerations:

Dabigatran etexilate is advocated alongside or without meals. If one encounters stomach upset and discomfort, Dabigatran should be served with meals to scale down such discomfort. Dabigatran etexilate should never be clubbed with milk products or milk.

Missed Dose:

Assuming that one unknowingly passes over the Dabigatran dose, look into and estimate the time left for the upcoming Dabigatran dose. If the succeeding Dabigatran dose is close by, disregard and bypass the overlooked dose. Ingest the overlooked Dabigatran dose only if the subsequent dose is over six hours away.

Overdose:

Dabigatran etexilate overdose may bring out overstated bleeding. Bloody vomit and stool often signal internal bleeding. The absence of a specific counteragent to tie down Dabigatran’s anticoagulant aspects showcases challenges in upturning the Dabigatran overdose intricacies. Nevertheless, dialysis (machine-aided blood filtering) can be instituted to extract and clear off Dabigatran etexilate.

Storage:

• Dabigatran Packaging: Blister strips and medicine bottles.

• Storage Temperature: 15 to 30 degrees Celsius (59 to 86 degrees Fahrenheit).

• Storage Condition: Away from moisture.

For Doctors:

Indications:

• Stroke (preventive - to gear down the risk in the presence of atrial fibrillation).

• Systemic embolism (preventive - for one with atrial fibrillation).

Dose:

• Creatinine Clearance Exceeding 30 Milliliters per Minute: 150 milligrams of Dabigatran etexilate twice a day.

• Creatinine Clearance Ranging Across 15 to 30 Milliliters per Minute: 75 milligrams of Dabigatran etexilate twice daily.

Dosing Considerations:

• Switching From Warfarin: Withdraw Warfarin and ensure that the INR (international normalized ratio) falls under two while actuating Dabigatran etexilate therapy.

• Switching From Parenteral Anticoagulant: Initiate Dabigatran therapy around two hours ahead of the estimated upcoming infusion time.

• Before Invasive Surgery: Suspend and hold up Dabigatran etexilate therapy up to five days before surgery to mark down the bleeding risk. The exact withdrawal period is contingent on the creatinine clearance rate and extensiveness of the surgery.

What Are the Pharmacological Aspects of Dabigatran Etexilate?

• Mechanism of Action: Dabigatran etexilate’s direct thrombin inhibitory aspects confer its capabilities to hold off thrombin from bringing out its coagulative potentialities. Dabigatran knocks around the thrombin molecules and secures bonds with them. This interaction restricts the thrombin’s potency to catalyze fibrinogen-fibrin transmutation. Furthermore, Dabigatran-thrombin interaction would also hamper the thrombin’s ability to actuate coagulation factors and disable thrombin’s actions. All these collaboratively subjugate the propensity for clot formation. It is these blood clots that could pull off a stroke or systemic embolism. This is how Dabigatran etexilate obviates systemic embolism and stroke.

• Pharmacodynamics: Being a latent drug form, Dabigatran etexilate hangs on in its dormant form until it gets hydrolyzed. Dabigatran secures a reversible mode of association with thrombin. Dabigatran could even intensify the fibrinolysis, thereby bolstering the disunion of fibrin-bound thrombin.

• Pharmacokinetics: Liver hydrolysis yieldsDabigatran etexilate’s therapeutically active element, Dabigatran. Three to seven percent is valued as Dabigatran’s bioavailability percentage. Upon Dabigatran’s delivery over an empty gut, the utmost Dabigatran concentration is brought off in one hour. Fatty meals could hold back Dabigatran’s utmost concentration. Dabigatran’s distribution is carried through plasma proteins. The transmutation of Dabigatran etexilate (pro-drug) to its reactive counterpart is fueled by liver esterase. Dabigatran etexilate’s conjugation may also bring out acyl glucuronides. It is through fecal and urinary pathways that Dabigatran gets expelled.

Toxicity:

Dabigatran etexilate’s toxicity profile unfolded an overdrawn hemorrhagic tendency. Dabigatran could even instigate a fatal bleed. The absence of specific Dabigatran antidote therapy makes Dabigatran etexilate toxicity troublesome. Plasma transfusion, dialysis, red blood cell transfusion, platelet concentrates, and surgical hemostasis are employed to offset the bleeding and blood loss.

Through animal studies, Dabigatran’s mutagenicity (inducing mutation), tumorigenicity (favoring tumor growth), and carcinogenicity (cancer-causing) have been looked over. Dabigatran was discovered to be immune to such toxic potentialities.

Clinical Studies:

The “randomized evaluation of long-term anticoagulant therapy (RE-LY)” extracted and documented Dabigatran’s efficacity. The study probed and weighted Dabigatran’s potency in opposition to Warfarin therapy. Those possessing the risk quotients for systemic embolism and stroke were methodically nominated for Dabigatran’s clinical study. The study endpoints showcased that Dabigatran could pull off speedy and superior anticoagulant traits. Both systemic embolism and stroke encounter projected substantial downturns with Dabigatran than Warfarin therapy. Furthermore, considering the safety concerns, Dabigatran revealed nominal side effects, unlike Warfarin, where one has to evaluate the coagulative specifications throughout the regimen systematically.

What Are the Contraindications of Dabigatran Etexilate?

• Dabigatran etexilate allergies.

• Active pathological bleeding.

Warnings and Precautions:

• Bleeding: As Dabigatran etexilate tapers down the blood’s coagulative potential, it heightens one’s hemorrhagic risk. Overstated bleeding is grave and exposes one to risk. Labor and multiple anticoagulant usage may escalate the bleeding risk. Bleeding signs must be scrutinized, and if needed, the Dabigatran etexilate dose ought to be offset. Dabigatran etexilate therapy must be lifted upon active pathological bleeding. Long-term Dabigatran etexilate therapy could pull off “life-threatening bleed.” Hypotension, anemia, and fatigue are often confronted as a repercussion of overstated bleeding.

• Surgery: One undergoing Dabigatran etexilate therapy is not straight away advocated for surgery. Having said that, surgery could be called for when Dabigatran's urgency surpasses the anticipated hemorrhage risk. Customarily, three to five days ahead of an operative procedure, Dabigatran etexilate ought to be suspended. This aids in turning down the anticoagulant traits charged by Dabigatran etexilate therapy. With Dabigatran etexilate suspension, superior hemostasis could be attained.

What Are the Drug Interactions of Dabigatran Etexilate?

• With P-Glycoprotein Inducers: Dabigatran’s exposure is reversed when advocated concurrently with the P-glycoprotein inducer. On that account, concurrent therapy may call forth Dabigatran dose revisions.

• With P-Glycoprotein Inhibitors: P-glycoprotein inhibitor and Dabigatran, when employed together, could substantially heighten Dabigatran’s exposure. Renal impairment may further inflate Dabigatran exposure, prompting toxicity threats. Therefore, it is cautioned to scale down the Dabigatran dose to half its recommended value. Nevertheless, deflect concurrent P-glycoprotein inhibitor and Dabigatran in severe renal impairment cases.

Specific Considerations:

• Dabigatran Etexilate During Pregnancy: Owing to pregnancy, Dabigatran etexilate is seated under category C. Nevertheless, there does not seem to be satisfactory data that uncovers Dabigatran etexilate’s dangers when advocated during pregnancy. Animal studies underscored fetal harm and stillbirth reports. Dabigatran shall be looked into in-depth for a definitive judgment, particularly about pregnant women.

• Dabigatran Etexilate During Lactation: Research data does not support Dabigatran’s behavior in nursing women. Dabigatran should only be advocated when the positive aspects override its anticipated complications.

• Dabigatran Etexilate in Pediatric Patients: Dabigatran’s therapeutic traits are questionable in pediatric patients. Hence, it stipulates additional scrutiny and is customarily not advocated.

• Dabigatran Etexilate in Geriatric Patients: Dabigatran etexilate therapy entails caution in elderly ones owing to renal impairment and other comorbidities. Geriatric patients reflected a heightened propensity for Dabigatran toxicities.