Dabigatran etexilate mesylate

What is Dabigatran etexilate mesylate?

• Dabigatran etexilate mesylate (Pradaxa) Capsules is a direct thrombin inhibitor used to treat and prevent blood clots and to prevent stroke in people with atrial fibrillation.

Dabigatran structure

Dabigatran etexilate structure

Dabigatran etexilate and dabigatran

Dabigatran binding pockets

What are the uses of this medicine?

Pradaxa is a prescription medicine that is used to: in adults:

• reduce the risk of stroke and blood clots in adults who have a medical condition called atrial fibrillation that is not caused by a heart valve problem. With atrial fibrillation, part of the heart does not beat the way it should. This can lead to blood clots forming and increase your risk of a stroke.
• treat blood clots in the veins of your legs (deep vein thrombosis) and lungs (pulmonary embolism) after you have been treated with an injectable medicine to treat your blood clots for 5 to 10 days.
• reduce your risk of blood clots from happening again in the veins of your legs (deep vein thrombosis) and lungs (pulmonary embolism) after you have received treatment for blood clots.
• help prevent blood clots in your legs (venous thrombosis) and lungs (pulmonary embolism) after you have just had hip replacement surgery.

in children:

• treat blood clots in children 8 years to less than 18 years of age who have received an injectable medicine to treat their blood clots for at least 5 days.
• reduce the risk of blood clots from happening again in children 8 years to less than 18 years of age who have received treatment for blood clots.

How does this medicine work?

• Dabigatran (da" bi gat' ran) is a potent direct inhibitor of thrombin, the final intermediate in blood coagulation.
• Dabigatran binds to the active site of thrombin and inactivates both fibrin-bound and unbound thrombin, unlike heparin that binds to the unbound thrombin only.
• Inhibiting thrombin prevents the conversion of fibrinogen to fibrin and subsequent cross linking of fibrin monomers, platelet activation and amplification of coagulation activation.
• Dabigatran itself is not absorbed from the gastrointestinal tract, but the prodrug dabigatran etexillate mesylate is absorbed and then converted to the active form by gut and plasma esterases.
• Dabigatran provides a reliable anticoagulant effect and monitoring of effect is not needed.

Who Should Not Use this medicine ?

This medicine cannot be used in patients who:

• currently have certain types of abnormal bleeding.
• have had a serious allergic reaction to any of the ingredients in Pradaxa.
• have ever had or plan to have a valve in your heart replaced with a mechanical (artificial) prosthetic heart valve.

What drug interactions can this medicine cause?

• The concomitant use of Pradaxa and P-gp inhibitors (e.g., rifampin) in patients with severe renal impairment (CrCl 15-30 mL/min) should be avoided.
• Avoid use of Pradaxa and P-gp inhibitors in patients with CrCl <50 mL/min.
• The concomitant use of Pradaxa and P-gp inhibitors (dronedarone or systemic ketoconazole),in patients with CrCl <50 mL/min should be avoided.
• The concomitant use of Pradaxa with P-gp inhibitors has not been studied in pediatric patients but may increase exposure to dabigatran.

Is this medicine FDA approved?

• Dabigatran etexilate was approved for use in the United States in 2010 and indications are for prevention of stroke and thromboembolic complications in patients with chronic atrial fibrillation not related to valvular heart disease.
• Thereafter, indications were extended to the treatment and prevention of deep venous thrombosis and pulmonary embolism.

How should this medicine be used?

Recommended dosage: Non-valvular Atrial Fibrillation in Adult Patients:

• For patients with CrCl >30 mL/min: 150 mg orally, twice daily
• For patients with CrCl 15-30 mL/min: 75 mg orally, twice daily

Treatment of DVT and PE in Adult Patients:

• For patients with CrCl >30 mL/min: 150 mg orally, twice daily after 5-10 days of parenteral anticoagulation

Reduction in the Risk of Recurrence of DVT and PE in Adult Patients:

• For patients with CrCl >30 mL/min: 150 mg orally, twice daily after previous treatment

Prophylaxis of DVT and PE Following Hip Replacement Surgery in Adult Patients:

• For patients with CrCl >30 mL/min: 110 mg orally first day, then 220 mg once daily

• Treatment of Pediatric VTE:
• For pediatric patients: weight-based dosage, twice daily after at least 5 days of parenteral anticoagulant

Reduction in the Risk of Recurrence of Pediatric VTE:

• For pediatric patients: weight-based dosage, twice daily after previous treatment

Administration:

• Pradaxa comes as capsules and oral pellets. If you have a child who is older than 8 years of age and who is prescribed Pradaxa, your healthcare provider will prescribe the type of Pradaxa that is right for your child.
• Your healthcare provider will decide how long you should take Pradaxa. Do not stop taking Pradaxa Capsules without first talking with your healthcare provider. Stopping Pradaxa may increase your risk of having a stroke or forming blood clots.
• Take Pradaxa Capsules exactly as prescribed by your healthcare provider.
• If Pradaxa is prescribed for your child, your healthcare provider will determine the correct dose of Pradaxa Capsules for your child based on their weight. Your healthcare provider may increase or decrease your child's dose as they grow during treatment and as needed.
• In adults: Take Pradaxa Capsules 2 times a day. If you are taking Pradaxa after hip replacement surgery, take Pradaxa 1 time a day.
• In children: Take Pradaxa Capsules 2 times a day. Take 1 dose in the morning and 1 dose in the evening about every 12 hours, at about the same time each day.
• You can take Pradaxa Capsules with or without food. Taking Pradaxa Capsules with food may help if you have an upset stomach.
• Swallow Pradaxa Capsules whole with a full glass of water. Tell your healthcare provider if you or your child are not able to swallow the capsules whole. Do not break, chew, or empty the pellets from the capsule.
• Do not run out of Pradaxa Capsules. Refill your prescription before you run out. If you plan to have surgery, or a medical or a dental procedure, tell your healthcare provider and dentist that you are taking Pradaxa. You may have to stop taking Pradaxa for a short time.
• If you miss a dose of Pradaxa Capsules, take it as soon as you remember. If your next dose is less than 6 hours away, skip the missed dose. Do not take two doses of Pradaxa Capsules at the same time.
• If you take too much Pradaxa Capsules, go to the nearest hospital emergency room or call your healthcare provider.
• Call your healthcare provider right away if you fall or injure yourself, especially if you hit your head. Your healthcare provider may need to check you.
• Pradaxa Capsules come in a bottle or in a blister package.
• Only open 1 bottle of Pradaxa Capsules at a time. Finish your opened bottle of Pradaxa Capsules before opening a new bottle.
• After opening a bottle of Pradaxa Capsules, use within 4 months.
• When it is time for you to take a dose of Pradaxa Capsules, only remove your prescribed dose of Pradaxa Capsules from your open bottle or blister package.
• Tightly close your bottle of Pradaxa Capsules right away after you take your dose.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Capsules: 75 mg, 110 mg and 150 mg

This medicine is available in fallowing brand namesː

• Pradaxa

What side effects can this medication cause?

The most common side effects of this medicine include: Common side effects of Pradaxa in adults and children include:

• indigestion, upset stomach, or burning
• stomach-area (abdominal) pain or discomfort

In children, common side effects also include:

• nausea, vomiting, or diarrhea

Pradaxa can cause serious side effects include:

• Allergic Reactions

What special precautions should I follow?

• Premature discontinuation of any oral anticoagulant, including Pradaxa, in the absence of adequate alternative anticoagulation increases the risk of thrombotic events.
• Pradaxa increases the risk of bleeding and can cause significant and, sometimes, fatal bleeding. Promptly evaluate any signs or symptoms of blood loss (e.g., a drop in hemoglobin and/or hematocrit or hypotension). Discontinue Pradaxa Capsules in patients with active pathological bleeding.
• When neuraxial anesthesia (spinal/epidural anesthesia) or spinal puncture is employed, patients treated with anticoagulant agents are at risk of developing an epidural or spinal hematoma which can result in long-term or permanent paralysis. If signs or symptoms of spinal hematoma are suspected, initiate urgent diagnosis and treatment including consideration for spinal cord decompression even though such treatment may not prevent or reverse neurological sequelae.
• The use of Pradaxa is contraindicated in all patients with mechanical prosthetic valves.
• Direct-acting oral anticoagulants (DOACs), including Pradaxa, are not recommended for use in patients with triple-positive antiphospholipid syndrome (APS).
• Dabigatran therapy has been associated with a low rate of serum enzyme elevations and rare instances of liver enzyme elevations and jaundice.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• hemorrhagic complications

Management of overdosage:

• In the event of hemorrhagic complications, initiate appropriate clinical support, discontinue treatment with Pradaxa, and investigate the source of bleeding.
• A specific reversal agent (idarucizumab) is available for adult patients.
• Dabigatran is primarily eliminated by the kidneys with a low plasma protein binding of approximately 35%.
• Hemodialysis can remove dabigatran; however, data supporting this approach are limited.

Can this medicine be used in pregnancy?

• The limited available data on Pradaxa use in pregnant women are insufficient to determine drug-associated risks for adverse developmental outcomes.
• It is not known if Pradaxa will harm your unborn baby.

Can this medicine be used in children?

• The safety and effectiveness of Pradaxa Capsules for the treatment and the reduction in risk of recurrence of venous thromboembolism have been established in pediatric patients 8 to less than 18 years of age.
• Safety and effectiveness of Pradaxa Capsules have not been established in pediatric patients with non-valvular atrial fibrillation or those who have undergone hip replacement surgery.

What are the active and inactive ingredients in this medicine?

• Active ingredient: dabigatran etexilate mesylate
• Inactive ingredients: acacia, dimethicone, hypromellose, hydroxypropyl cellulose, talc, and tartaric acid. The capsule shell is composed of carrageenan, hypromellose, potassium chloride, titanium dioxide, black edible ink, and FD&C Blue No. 2 (150 mg and 110 mg capsules only).

Who manufactures and distributes this medicine?

• Distributed by:

Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT USA

• Pradaxa is a registered trademark of and used under license from Boehringer Ingelheim International GmbH.

What should I know about storage and disposal of this medication?

• Store Pradaxa Capsules at room temperature 68°F to 77°F (20°C to 25°C).
• After opening the bottle, use Pradaxa Capsules within 4 months. Safely throw away any unused Pradaxa Capsules after 4 months.
• Keep Pradaxa Capsules in the original bottle or blister package to keep them dry (protect the capsules from moisture). Do not put Pradaxa Capsules in pill boxes or pill organizers.
• Tightly close your bottle of Pradaxa Capsules right away after you take your dose.

• Dailymed label info on Dabigatran etexilate mesylate
• FDA Dabigatran etexilate mesylate

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