Pradaxa: Package Insert and Label Information

PRADAXA- dabigatran etexilate mesylate pellet
Boehringer Ingelheim Pharmaceuticals, Inc.

(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. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:

• use of indwelling epidural catheters
• concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants
• a history of traumatic or repeated epidural or spinal punctures
• a history of spinal deformity or spinal surgery
• optimal timing between the administration of PRADAXA and neuraxial procedures is not known [see Warnings and Precautions (5.3)].

Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary [see Warnings and Precautions (5.3)].

Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated [see Warnings and Precautions (5.3)].

1 INDICATIONS AND USAGE

1.1 Treatment of Venous Thromboembolic Events in Pediatric Patients

PRADAXA Oral Pellets are indicated for the treatment of venous thromboembolic events (VTE) in pediatric patients aged 3 months to less than 12 years of age who have been treated with a parenteral anticoagulant for at least 5 days.

1.2 Reduction in the Risk of Recurrence of Venous Thromboembolic Events in Pediatric Patients

PRADAXA Oral Pellets are indicated to reduce the risk of recurrence of VTE in pediatric patients aged 3 months to less than 12 years of age who have been previously treated.

2 DOSAGE AND ADMINISTRATION

2.1 Important Dosage Information

Dabigatran etexilate is available in different dosage forms and not all dosage forms are approved for the same indications and age groups. In addition, there are differences between the dosage forms with respect to dosing due to differences in bioavailability. Do not substitute different dosage forms (for example, capsules) for oral pellets on a milligram-to-milligram basis and do not combine more than one dosage form to achieve the total dose [see Clinical Pharmacology (12.3)].

2.2 Recommended PRADAXA Oral Pellets Dose for Pediatric Patients

PRADAXA Oral Pellets can be used in pediatric patients aged 3 months to less than 12 years as soon as they are able to swallow soft food. For the treatment of VTE in pediatric patients, treatment should be initiated following treatment with a parenteral anticoagulant for at least 5 days. For reduction in risk of recurrence of VTE, treatment should be initiated following previous treatment.

The recommended dose of PRADAXA Oral Pellets is based on the patient’s age and actual weight as shown in the tables below. PRADAXA Oral Pellets is administered twice daily. Adjust the dose according to age and actual weight as treatment progresses.

Table 1 Age- and Weight-Based Dosing for PRADAXA Oral Pellets for Pediatric Patients less than 2 Years Old

Actual Weight (kg)	Age (in months)	Dose (mg) twice daily	Number of Packets Needed
3 kg to less than 4 kg	3 to less than 6 months	30 mg	one 30 mg packet twice daily
4 kg to less than 5 kg	3 to less than 10 months	40 mg	one 40 mg packet twice daily
5 kg to less than 7 kg	3 to less than 5 months	40 mg	one 40 mg packet twice daily
	5 to less than 24 months	50 mg	one 50 mg packet twice daily
7 kg to less than 9 kg	3 to less than 4 months	50 mg	one 50 mg packet twice daily
	4 to less than 9 months	60 mg	two 30 mg packets twice daily
	9 to less than 24 months	70 mg	one 30 mg packet plus one 40 mg packet twice daily
9 kg to less than 11 kg	5 to less than 6 months	60 mg	two 30 mg packets twice daily
	6 to less than 11 months	80 mg	two 40 mg packets twice daily
	11 to less than 24 months	90 mg	one 40 mg packet plus one 50 mg packet twice daily
11 kg to less than 13 kg	8 to less than 18 months	100 mg	two 50 mg packets twice daily
	18 to less than 24 months	110 mg	one 110 mg packet twice daily
13 kg to less than 16 kg	10 to less than 11 months	100 mg	two 50 mg packets twice daily
	11 to less than 24 months	140 mg	one 30 mg packet plus one 110 mg packet twice daily
16 kg to less than 21 kg	12 to less than 24 months	140 mg	one 30 mg packet plus one 110 mg packet twice daily
21 kg to less than 26 kg	18 to less than 24 months	180 mg	one 30 mg packet plus one 150 mg packet twice daily

Table 2 Weight-Based Dosing for PRADAXA Oral Pellets for Pediatric Patients between 2 Years to less than 12 Years Old

Actual Weight (kg)	Dose (mg) twice daily	Number of Packets Needed
7 kg to less than 9 kg	70 mg	one 30 mg packet plus one 40 mg packet twice daily
9 kg to less than 11 kg	90 mg	one 40 mg packet plus one 50 mg packet twice daily
11 kg to less than 13 kg	110 mg	one 110 mg packet twice daily
13 kg to less than 16 kg	140 mg	one 30 mg packet plus one 110 mg packet twice daily
16 kg to less than 21 kg	170 mg	one 20 mg packet plus one 150 mg packet twice daily
21 kg to less than 41 kg	220 mg	two 110 mg packets twice daily
41 kg or greater	260 mg	one 110 mg packet plus one 150 mg packet twice daily

Evaluation of the extent of anticoagulation in pediatric patients on PRADAXA Oral Pellets may be accomplished using dTT or ECT, and not INR [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.2)].

2.3 Dosage Adjustments

Pediatric Patients with Renal Impairment

Assess renal function prior to initiation of treatment with PRADAXA Oral Pellets. Periodically assess renal function as clinically indicated (i.e., more frequently in clinical situations that may be associated with a decline in renal function) and adjust therapy accordingly. Discontinue PRADAXA Oral Pellets in patients who develop acute renal failure while on PRADAXA Oral Pellets and consider alternative anticoagulant therapy.

Prior to the initiation of treatment with PRADAXA Oral Pellets, estimate the glomerular filtration rate (eGFR) using the Schwartz formula, eGFR (Schwartz) = (0.413 × height in cm) / serum creatinine in mg/dL.

Due to lack of data in pediatric patients with an eGFR < 50 mL/min/1.73m² and the risk of increased exposure, avoid use of PRADAXA Oral Pellets in these patients. Treat patients with an eGFR > 50 mL/min/1.73m² with the dose according to Tables 1 and 2 [see Dosage and Administration (2.2)].

2.4 Administration

PRADAXA Oral Pellets are administered twice daily, one dose in the morning and one dose in the evening, at approximately the same time every day. The dosing interval should be as close to 12 hours as possible.

If a dose of PRADAXA Oral Pellets is not taken at the scheduled time, the dose should be taken as soon as possible on the same day; the missed dose should be skipped if it cannot be taken at least 6 hours before the next scheduled dose. The dose of PRADAXA Oral Pellets should not be doubled to make up for a missed dose.

If a partial dose has been taken, a second dose should not be administered at that time. The next dose should be taken as scheduled approximately 12 hours later.

The prepared medication should be given before meals to ensure that the patient takes the full dose.

PRADAXA Oral Pellets should be administered immediately after mixing or within 30 minutes after mixing. If the PRADAXA dose is not administered within 30 minutes of mixing, the dose should be discarded, and a new dose prepared.

PRADAXA Oral Pellets should be administered with only specific soft foods or apple juice.

Administration with soft foods

PRADAXA Oral Pellets may be mixed with two teaspoons of the following soft foods at room temperature:

• Mashed carrots
• Apple sauce
• Mashed banana

Administration with apple juice

PRADAXA Oral Pellets may be spooned directly into the patient’s mouth and swallowed with apple juice or added to approximately 1-2 ounces of apple juice for drinking.

PRADAXA Oral Pellets should not be administered:

• via syringes or feeding tubes
• with milk, milk products, or soft foods containing milk products

Instruct patients/caregivers to discard the desiccant once the package is opened.

See Instructions for Use.

2.5 Converting from or to Warfarin

When converting patients from warfarin therapy to PRADAXA Oral Pellets, discontinue warfarin and start PRADAXA Oral Pellets when the INR is below 2.0.

When converting from PRADAXA Oral Pellets to warfarin, adjust the starting time of warfarin as follows:

• For eGFR ≥50 mL/min/1.73m² , start warfarin 3 days before discontinuing PRADAXA Oral Pellets.
• Patients with an eGFR <50 mL/min/1.73m² have not been studied. Avoid use of PRADAXA Oral Pellets in these patients.

Because PRADAXA Oral Pellets can increase INR, the INR will better reflect warfarin’s effect only after PRADAXA Oral Pellets have been stopped for at least 2 days [see Clinical Pharmacology (12.2)].

2.6 Converting from or to Parenteral Anticoagulants

For pediatric patients currently receiving a parenteral anticoagulant, start PRADAXA Oral Pellets 0 to 2 hours before the time that the next dose of the parenteral drug was to have been administered or at the time of discontinuation of a continuously administered parenteral drug (e.g., intravenous unfractionated heparin).

For pediatric patients currently taking PRADAXA Oral Pellets, wait 12 hours after the last dose before switching to a parenteral anticoagulant [see Clinical Pharmacology (12.3)].

2.7 Discontinuation for Surgery and Other Interventions

If possible, discontinue PRADAXA Oral Pellets before invasive or surgical procedures because of the increased risk of bleeding. For pediatric patients, PRADAXA Oral Pellets should be stopped 24 hours before an elective surgery (eGFR > 80 mL/min/1.73m²) or 2 days before an elective surgery (eGFR 50-80 mL/min/1.73m²). Pediatric patients with an eGFR < 50 mL/min/1.73m² have not been studied, avoid use of PRADAXA Oral Pellets in these patients.

Consider longer times for patients undergoing major surgery, spinal puncture, or placement of a spinal or epidural catheter or port, in whom complete hemostasis may be required [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

If surgery cannot be delayed, there is an increased risk of bleeding [see Warnings and Precautions (5.2)]. This risk of bleeding should be weighed against the urgency of intervention [see Warnings and Precautions (5.1, 5.3)]. In adults, a specific reversal agent (idarucizumab) is available in case of emergency surgery or urgent procedures when reversal of the anticoagulant effect of dabigatran is needed. Efficacy and safety of idarucizumab have not been established in pediatric patients [see Warnings and Precautions (5.2)]. Refer to the idarucizumab prescribing information for additional information. Restart PRADAXA Oral Pellets as soon as medically appropriate.

3 DOSAGE FORMS AND STRENGTHS

PRADAXA Oral Pellets are available in the following strengths:

• 20 mg yellowish pellets in a packet
• 30 mg yellowish pellets in a packet
• 40 mg yellowish pellets in a packet
• 50 mg yellowish pellets in a packet
• 110 mg yellowish pellets in a packet
• 150 mg yellowish pellets in a packet