Prescription Drug Information: Pradaxa (Page 4 of 9)

6.2 Postmarketing Experience

The following adverse reactions have been identified during post approval use of PRADAXA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following adverse reactions have been identified during post approval use of PRADAXA: angioedema, thrombocytopenia, esophageal ulcer, alopecia, neutropenia, agranulocytosis.

7 DRUG INTERACTIONS

7.1 Reduction of Risk of Stroke and Systemic Embolism in Non-valvular Atrial Fibrillation in Adult Patients

The concomitant use of PRADAXA with P-gp inducers (e.g., rifampin) reduces exposure to dabigatran and should generally be avoided [see Clinical Pharmacology (12.3)].

P-gp inhibition and impaired renal function are the major independent factors that result in increased exposure to dabigatran [see Clinical Pharmacology (12.3)]. Concomitant use of P-gp inhibitors in patients with renal impairment is expected to produce increased exposure of dabigatran compared to that seen with either factor alone.

In patients with moderate renal impairment (CrCl 30-50 mL/min), reduce the dose of PRADAXA to 75 mg twice daily when administered concomitantly with the P-gp inhibitors dronedarone or systemic ketoconazole. The use of the P-gp inhibitors verapamil, amiodarone, quinidine, clarithromycin, and ticagrelor does not require a dose adjustment of PRADAXA. These results should not be extrapolated to other P-gp inhibitors [see Warnings and Precautions (5.5), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].

The concomitant use of PRADAXA and P-gp inhibitors in patients with severe renal impairment (CrCl 15-30 mL/min) should be avoided [see Warnings and Precautions (5.5), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].

7.2 Treatment and Reduction in the Risk of Recurrence of Deep Venous Thrombosis and Pulmonary Embolism in Adult Patients

Avoid use of PRADAXA and P-gp inhibitors in patients with CrCl <50 mL/min [see Warnings and Precautions (5.5), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].

7.3 Prophylaxis of Deep Vein Thrombosis and Pulmonary Embolism in Adult Patients Following Hip Replacement Surgery

In patients with CrCl ≥50 mL/min who have concomitant administration of P-gp inhibitors such as dronedarone or systemic ketoconazole, it may be helpful to separate the timing of administration of PRADAXA and the P-gp inhibitor by several hours. The concomitant use of PRADAXA and P-gp inhibitors in patients with CrCl <50 mL/min should be avoided [see Warnings and Precautions (5.5), Use in Specific Populations (8.6) and Clinical Pharmacology (12.2, 12.3)].

7.4 Treatment and Reduction in Risk of Recurrence of VTE in Pediatric Patients

The concomitant use of PRADAXA with P-gp inhibitors has not been studied in pediatric patients but may increase exposure to dabigatran [see Warnings and Precautions (5.5)].

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

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).

8.2 Lactation

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.

8.3 Females and Males of Reproductive Potential

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.

8.4 Pediatric Use

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.

8.5 Geriatric Use

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)].

8.6 Renal Impairment

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/1.73m2. 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)].

RxDrugLabels.com provides trustworthy package insert and label information about marketed prescription drugs as submitted by manufacturers to the U.S. Food and Drug Administration. Package information is not reviewed or updated separately by RxDrugLabels.com. Every individual prescription drug label and package insert entry contains a unique identifier which can be used to secure further details directly from the U.S. National Institutes of Health and/or the FDA.

As a leading independent provider of trustworthy medication information, we source our database directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. RxDrugLabels.com provides the full prescription-only subset of the FDA's repository. Medication information provided here is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2023. All Rights Reserved.