PRADAXA- dabigatran etexilate mesylate capsule

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

DABIGATRAN ETEXILATE MESYLATE (UNII: SC7NUW5IIT) (DABIGATRAN - UNII:I0VM4M70GC)

Available from:

Boehringer Ingelheim Pharmaceuticals Inc.

INN (International Name):

DABIGATRAN ETEXILATE MESYLATE

Composition:

DABIGATRAN ETEXILATE 75 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

PRADAXA Capsules is indicated to reduce the risk of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation. PRADAXA Capsules is indicated for the treatment of deep venous thrombosis and pulmonary embolism in adult patients who have been treated with a parenteral anticoagulant for 5-10 days. PRADAXA Capsules is indicated to reduce the risk of recurrence of deep venous thrombosis and pulmonary embolism in adult patients who have been previously treated. PRADAXA Capsules is indicated for the prophylaxis of deep vein thrombosis and pulmonary embolism in adult patients who have undergone hip replacement surgery. PRADAXA Capsules is indicated for the treatment of venous thromboembolic events (VTE) in pediatric patients 8 to less than 18 years of age who have been treated with a parenteral anticoagulant for at least 5 days [see Dosage and Administration (2.3)] . PRADAXA Capsules is indicated to reduce the risk of recurrence of VTE in pediatric patients 8 to less than 18 years of age who have been previously treated [see Dosage and Administration (2.3)] . PRADAXA is contraindicated in patients with: - Active pathological bleeding [see Warnings and Precautions (5.2) and Adverse Reactions (6.1)] - History of a serious hypersensitivity reaction to dabigatran, dabigatran etexilate, or to one of the excipients of the product (e.g., anaphylactic reaction or anaphylactic shock) [see Adverse Reactions (6.1)] - Mechanical prosthetic heart valve [see Warnings and Precautions (5.4)] Risk Summary The limited available data on PRADAXA use in pregnant women are insufficient to determine drug-associated risks for adverse developmental outcomes. There are risks to the mother associated with untreated venous thromboembolism in pregnancy and a risk of hemorrhage in the mother and fetus associated with the use of anticoagulants (see Clinical Considerations) . In pregnant rats treated from implantation until weaning, dabigatran increased the number of dead offspring and caused excess vaginal/uterine bleeding close to parturition at an exposure 2.6 times the human exposure. At a similar exposure, dabigatran decreased the number of implantations when rats were treated prior to mating and up to implantation (gestation Day 6). Dabigatran administered to pregnant rats and rabbits during organogenesis up to exposures 8 and 13 times the human exposure, respectively, did not induce major malformations. However, the incidence of delayed or irregular ossification of fetal skull bones and vertebrae was increased in the rat (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Pregnancy confers an increased risk for thromboembolism that is higher for women with underlying thromboembolic disease and certain high-risk pregnancy conditions. Published data describe that women with a previous history of venous thrombosis are at high risk for recurrence during pregnancy. Fetal/Neonatal adverse reaction Use of anticoagulants, including PRADAXA, may increase the risk of bleeding in the fetus and neonate. Monitor neonates for bleeding [see Warnings and Precautions (5.2)]. Labor or delivery All patients receiving anticoagulants, including pregnant women, are at risk for bleeding. PRADAXA use during labor or delivery in women who are receiving neuraxial anesthesia may result in epidural or spinal hematomas. Consider discontinuation or use of shorter acting anticoagulant as delivery approaches [see Warnings and Precautions (5.2, 5.3)] . Data Animal Data Dabigatran has been shown to decrease the number of implantations when male and female rats were treated at a dosage of 70 mg/kg (about 2.6 to 3.0 times the human exposure at MRHD of 300 mg/day based on area under the curve [AUC] comparisons) prior to mating and up to implantation (gestation Day 6). Treatment of pregnant rats after implantation with dabigatran at the same dose increased the number of dead offspring and caused excess vaginal/uterine bleeding close to parturition. Dabigatran administered to pregnant rats and rabbits during organogenesis up to maternally toxic doses of 200 mg/kg (8 and 13 times the human exposure, respectively, at a MRHD of 300 mg/day based on AUC comparisons) did not induce major malformations, but increased the incidence of delayed or irregular ossification of fetal skull bones and vertebrae in the rat. Death of offspring and mother rats during labor in association with uterine bleeding occurred during treatment of pregnant rats from implantation (gestation Day 7) to weaning (lactation Day 21) with dabigatran at a dose of 70 mg/kg (about 2.6 times the human exposure at MRHD of 300 mg/day based on AUC comparisons). Risk Summary There are no data on the presence of dabigatran in human milk, the effects on the breastfed child, or on milk production. Dabigatran and/or its metabolites were present in rat milk. Breastfeeding is not recommended during treatment with PRADAXA. Females of reproductive potential requiring anticoagulation should discuss pregnancy planning with their physician. The risk of clinically significant uterine bleeding, potentially requiring gynecological surgical interventions, identified with oral anticoagulants including PRADAXA should be assessed in females of reproductive potential and those with abnormal uterine bleeding. 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. Use of PRADAXA for this indication is supported by evidence from adequate and well-controlled studies in pediatric patients. These studies included an open-label, randomized, parallel-group study and an open-label, single-arm safety study [see Adverse Reactions (6.1) and Clinical Studies (14.4, 14.5)] . Other age-appropriate pediatric dosage forms of dabigatran etexilate are available for pediatric patients less than 8 years of age for these indications. 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. Of the total number of patients in the RE-LY study, 82% were 65 and over, while 40% were 75 and over. The risk of stroke and bleeding increases with age, but the risk-benefit profile is favorable in all age groups [see Warnings and Precautions (5), Adverse Reactions (6.1), and Clinical Studies (14.1)] . Reduction of Risk of Stroke and Systemic Embolism in Non-valvular Atrial Fibrillation in Adult Patients No dose adjustment of PRADAXA is recommended in patients with mild or moderate renal impairment [see Clinical Pharmacology (12.3)] . Reduce the dose of PRADAXA in patients with severe renal impairment (CrCl 15-30 mL/min) [see Dosage and Administration (2.2, 2.4) and Clinical Pharmacology (12.3)] . Dosing recommendations for patients with CrCl < 15 mL/min or on dialysis cannot be provided. Adjust dose appropriately in patients with renal impairment receiving concomitant P-gp inhibitors [see Warnings and Precautions (5.5), Drug Interactions (7.1), and Clinical Pharmacology (12.3)]. Treatment and Reduction in the Risk of Recurrence of Deep Venous Thrombosis and Pulmonary Embolism in Adult Patients Patients with severe renal impairment (CrCl ≤ 30 mL/min) were excluded from RE-COVER. Dosing recommendations for patients with CrCl ≤ 30 mL/min or on dialysis cannot be provided. Avoid use of PRADAXA with concomitant P-gp inhibitors in patients with CrCl < 50 mL/min [see Warnings and Precautions (5.5), Drug Interactions (7.2), and Clinical Pharmacology (12.3)]. Prophylaxis of Deep Vein Thrombosis and Pulmonary Embolism in Adult Patients Following Hip Replacement Surgery Patients with severe renal impairment (CrCl < 30 mL/min) were excluded from RE-NOVATE and RE-NOVATE II. Dosing recommendations for patients with CrCl < 30 mL/min or on dialysis cannot be provided. Avoid use of PRADAXA with concomitant P-gp inhibitors in patients with CrCl < 50 mL/min [see Warnings and Precautions (5.5), Drug Interactions (7.3), and Clinical Pharmacology (12.2, 12.3)]. Treatment and Reduction in the Risk of Recurrence of VTE in Pediatric Patients PRADAXA has not been studied in pediatric patients with eGFR < 50 mL/min/1.73 m2 . Reduced renal function could increase exposure. Dosing recommendations cannot be provided for treatment of these patients. Avoid use of PRADAXA Capsules in these patients [see Dosage and Administration (2.4)].

Product summary:

PRADAXA 75 mg capsules have a white opaque cap imprinted with the Boehringer Ingelheim company symbol and a white opaque body imprinted with "R75". The color of the imprinting is black. The capsules are supplied in the packages listed: PRADAXA 110 mg capsules have a light blue opaque cap imprinted with the Boehringer Ingelheim company symbol and a light blue opaque body imprinted with "R110". The color of the imprinting is black. The capsules are supplied in the packages listed: PRADAXA 150 mg capsules have a light blue opaque cap imprinted with the Boehringer Ingelheim company symbol and a white opaque body imprinted with "R150". The color of the imprinting is black. The capsules are supplied in the packages listed: Bottles Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Once opened, the product must be used within 4 months. Keep the bottle tightly closed. Store in the original package to protect from moisture. Blisters Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Store in the original package to protect from moisture.

Authorization status:

New Drug Application

Patient Information leaflet

Boehringer Ingelheim Pharmaceuticals Inc.
----------
This Medication Guide has been approved by the U.S. Food and Drug
Administration.
Revised:
November 2023
MEDICATION GUIDE
PRADAXA (pra dax a)
(dabigatran etexilate)
Capsules
This Medication Guide is for PRADAXA Capsules. If your healthcare
provider prescribes PRADAXA
Oral Pellets for you, read the Medication Guide that comes with your
medicine.
Read this Medication Guide before you start taking PRADAXA Capsules
and each time you get a refill.
There may be new information. This Medication Guide does not take the
place of talking with your
healthcare provider about your medical condition or your treatment.
What is the most important information I should know about PRADAXA?
•
People with atrial fibrillation (a type of irregular heartbeat) are at
an increased risk of forming a
blood clot in the heart, which can travel to the brain, causing a
stroke, or to other parts of the
body. PRADAXA lowers your chance of having a stroke by helping to
prevent clots from
forming. If you stop taking PRADAXA, you may have increased risk of
forming a clot in your
blood.
Do not stop taking PRADAXA Capsules without talking to the healthcare
provider who
prescribes it for you. Stopping PRADAXA increases your risk of having
a stroke.
PRADAXA may need to be stopped, if possible, before surgery or a
medical or dental procedure.
Ask the healthcare provider who prescribed PRADAXA for you when you
should stop taking it.
Your healthcare provider will tell you when you may start taking
PRADAXA again after your
surgery or procedure. If you have to stop taking PRADAXA, your
healthcare provider may
prescribe another medicine to help prevent a blood clot from forming.
•
PRADAXA can cause bleeding which can be serious, and sometimes lead to
death. This is
because PRADAXA is a blood thinner medicine that lowers the chance of
blood clots forming in
your body.
•
You may have a higher risk of bleeding if you take PRADAXA and:
•
are over 75 years old
•
have kidney problems
•
have stomach or

Summary of Product characteristics

PRADAXA- DABIGATRAN ETEXILATE MESYLATE CAPSULE
BOEHRINGER INGELHEIM PHARMACEUTICALS INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
PRADAXA CAPSULES
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR PRADAXA
CAPSULES.
PRADAXA (DABIGATRAN ETEXILATE) CAPSULES, FOR ORAL USE
INITIAL U.S. APPROVAL: 2010
WARNING: (A) PREMATURE DISCONTINUATION OF PRADAXA INCREASES THE RISK
OF
THROMBOTIC EVENTS, AND (B) SPINAL/EPIDURAL HEMATOMA
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING_
(A) PREMATURE DISCONTINUATION OF PRADAXA INCREASES THE RISK OF
THROMBOTIC
EVENTS: PREMATURE DISCONTINUATION OF ANY ORAL ANTICOAGULANT, INCLUDING
PRADAXA,
INCREASES THE RISK OF THROMBOTIC EVENTS. TO REDUCE THIS RISK, CONSIDER
COVERAGE WITH
ANOTHER ANTICOAGULANT IF PRADAXA IS DISCONTINUED FOR A REASON OTHER
THAN PATHOLOGICAL
BLEEDING OR COMPLETION OF A COURSE OF THERAPY (2.6, 2.7, 2.8, 5.1).
(B) SPINAL/EPIDURAL HEMATOMA: EPIDURAL OR SPINAL HEMATOMAS MAY OCCUR
IN PATIENTS
TREATED WITH PRADAXA WHO ARE RECEIVING NEURAXIAL ANESTHESIA OR
UNDERGOING SPINAL
PUNCTURE. THESE HEMATOMAS MAY RESULT IN LONG-TERM OR PERMANENT
PARALYSIS (5.3).
MONITOR PATIENTS FREQUENTLY FOR SIGNS AND SYMPTOMS OF NEUROLOGICAL
IMPAIRMENT AND IF
OBSERVED, TREAT URGENTLY. CONSIDER THE BENEFITS AND RISKS BEFORE
NEURAXIAL INTERVENTION
IN PATIENTS WHO ARE OR WHO NEED TO BE ANTICOAGULATED (5.3).
INDICATIONS AND USAGE
PRADAXA Capsules is a direct thrombin inhibitor indicated:
To reduce the risk of stroke and systemic embolism in adult patients
with non-valvular atrial fibrillation
(1.1)
For the treatment of deep venous thrombosis (DVT) and pulmonary
embolism (PE) in adult patients
who have been treated with a parenteral anticoagulant for 5-10 days
(1.2)
To reduce the risk of recurrence of DVT and PE in adult patients who
have been previously treated (1.3)
For the prophylaxis of DVT and PE in adult patients who have undergone
hip replacement surgery (1.4)
For the treatment of venous thromboembolic