Brineura

• Administration of BRINEURA should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. (
  2.1 Recommendations Prior to BRINEURA Treatment

  • Administration of BRINEURA should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis.
  • Initiate BRINEURA in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment

    [see Warnings and Precautions (5.1)]

    .
  • BRINEURA should be administered by or under the supervision of a physician experienced in intraventricular administration via a surgically implanted intraventricular access device system which consists of the reservoir and catheter components
    [see Dosage and Administration (2.6)]
    .
  • Premedication of patients with antihistamines with or without antipyretics or corticosteroids is recommended 30 to 60 minutes prior to the start of infusion
    [see Warnings and Precautions (5.1, 5.5)]
    .
  • Aseptic technique must be strictly observed during preparation and administration
    [see Dosage and Administration (2.6)]
    .
  • Prior to each infusion of BRINEURA, inspect the scalp for signs of intraventricular access device reservoir leakage, failure or potential infection
    [see Warnings and Precautions (5.2, 5.3)]
    .
  • Prior to each infusion of BRINEURA and when clinically indicated, obtain a sample of CSF for cell count and culture
    [see Warnings and Precautions (5.2)]
    .
  • Replace the intraventricular access device reservoir prior to 4 years of single-puncture administrations
    [see Warnings and Precautions (5.3)].
  )
• BRINEURA should be administered by or under the supervision of a physician experienced in intraventricular administration. (
  2.1 Recommendations Prior to BRINEURA Treatment

  • Administration of BRINEURA should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis.
  • Initiate BRINEURA in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment

    [see Warnings and Precautions (5.1)]

    .
  • BRINEURA should be administered by or under the supervision of a physician experienced in intraventricular administration via a surgically implanted intraventricular access device system which consists of the reservoir and catheter components
    [see Dosage and Administration (2.6)]
    .
  • Premedication of patients with antihistamines with or without antipyretics or corticosteroids is recommended 30 to 60 minutes prior to the start of infusion
    [see Warnings and Precautions (5.1, 5.5)]
    .
  • Aseptic technique must be strictly observed during preparation and administration
    [see Dosage and Administration (2.6)]
    .
  • Prior to each infusion of BRINEURA, inspect the scalp for signs of intraventricular access device reservoir leakage, failure or potential infection
    [see Warnings and Precautions (5.2, 5.3)]
    .
  • Prior to each infusion of BRINEURA and when clinically indicated, obtain a sample of CSF for cell count and culture
    [see Warnings and Precautions (5.2)]
    .
  • Replace the intraventricular access device reservoir prior to 4 years of single-puncture administrations
    [see Warnings and Precautions (5.3)].
  )
• Premedication of patients with antihistamines with or without antipyretics or corticosteroids is recommended. (
  2.1 Recommendations Prior to BRINEURA Treatment

  • Administration of BRINEURA should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis.
  • Initiate BRINEURA in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment

    [see Warnings and Precautions (5.1)]

    .
  • BRINEURA should be administered by or under the supervision of a physician experienced in intraventricular administration via a surgically implanted intraventricular access device system which consists of the reservoir and catheter components
    [see Dosage and Administration (2.6)]
    .
  • Premedication of patients with antihistamines with or without antipyretics or corticosteroids is recommended 30 to 60 minutes prior to the start of infusion
    [see Warnings and Precautions (5.1, 5.5)]
    .
  • Aseptic technique must be strictly observed during preparation and administration
    [see Dosage and Administration (2.6)]
    .
  • Prior to each infusion of BRINEURA, inspect the scalp for signs of intraventricular access device reservoir leakage, failure or potential infection
    [see Warnings and Precautions (5.2, 5.3)]
    .
  • Prior to each infusion of BRINEURA and when clinically indicated, obtain a sample of CSF for cell count and culture
    [see Warnings and Precautions (5.2)]
    .
  • Replace the intraventricular access device reservoir prior to 4 years of single-puncture administrations
    [see Warnings and Precautions (5.3)].
  )
• Prior to each infusion, inspect the scalp for signs of intraventricular access device reservoir leakage, failure, or potential infection. (
  2.1 Recommendations Prior to BRINEURA Treatment

  • Administration of BRINEURA should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis.
  • Initiate BRINEURA in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment

    [see Warnings and Precautions (5.1)]

    .
  • BRINEURA should be administered by or under the supervision of a physician experienced in intraventricular administration via a surgically implanted intraventricular access device system which consists of the reservoir and catheter components
    [see Dosage and Administration (2.6)]
    .
  • Premedication of patients with antihistamines with or without antipyretics or corticosteroids is recommended 30 to 60 minutes prior to the start of infusion
    [see Warnings and Precautions (5.1, 5.5)]
    .
  • Aseptic technique must be strictly observed during preparation and administration
    [see Dosage and Administration (2.6)]
    .
  • Prior to each infusion of BRINEURA, inspect the scalp for signs of intraventricular access device reservoir leakage, failure or potential infection
    [see Warnings and Precautions (5.2, 5.3)]
    .
  • Prior to each infusion of BRINEURA and when clinically indicated, obtain a sample of CSF for cell count and culture
    [see Warnings and Precautions (5.2)]
    .
  • Replace the intraventricular access device reservoir prior to 4 years of single-puncture administrations
    [see Warnings and Precautions (5.3)].
  )
• Recommended BRINEURA dosage is 300 mg administered once every other week as an intraventricular infusion. In patients less than 2 years of age, lower doses are recommended. (
  2.2 Recommended Dosage and Administration

  The recommended dosage of BRINEURA in pediatric patients is provided in Table 1. The dose is administered once every other week by intraventricular infusion.

  BRINEURA is not recommended in patients less than 37 weeks post-menstrual age (gestational age at birth plus post-natal age) or those weighing less than 2.5 kg

  [see Use in Specific Populations (8.4)].

  Administer BRINEURA first followed by infusion of the Intraventricular Electrolytes. The complete BRINEURA infusion, including the required infusion of Intraventricular Electrolytes, is approximately 2 to 4.5 hours, depending on the dose and volume administered. See Table 1for the appropriate volume and infusion rate. For volumes that are not whole numbers,

  see Dosage and Administration (2.6)

  .

  Table 1: BRINEURA Dose, Volume, and Infusion Rate by Age

  Age groups	BRINEURA dose administered every other week	Volume of BRINEURA solution	Infusion rate
  Birth to < 6 months	100 mg	3.3 mL	1.25 mL/hr
  6 months to < 1 year	150 mg	5 mL	2.5 mL/hr
  1 year to < 2 years	200 mg (first 4 doses)	6.7 mL (first 4 doses)	2.5 mL/hr
  	300 mg (subsequent doses)	10 mL (subsequent doses)
  2 years and older	300 mg	10 mL	2.5 mL/hr

  Missed Dose

  If one or more doses are missed, restart BRINEURA treatment as soon as possible, maintaining the 2-week interval between infusions thereafter.
  )
• Dosing is not recommended in patients less than 37 weeks post-menstrual age or those weighing less than 2.5 kg. (
  2.2 Recommended Dosage and Administration

  The recommended dosage of BRINEURA in pediatric patients is provided in Table 1. The dose is administered once every other week by intraventricular infusion.

  BRINEURA is not recommended in patients less than 37 weeks post-menstrual age (gestational age at birth plus post-natal age) or those weighing less than 2.5 kg

  [see Use in Specific Populations (8.4)].

  Administer BRINEURA first followed by infusion of the Intraventricular Electrolytes. The complete BRINEURA infusion, including the required infusion of Intraventricular Electrolytes, is approximately 2 to 4.5 hours, depending on the dose and volume administered. See Table 1for the appropriate volume and infusion rate. For volumes that are not whole numbers,

  see Dosage and Administration (2.6)

  .

  Table 1: BRINEURA Dose, Volume, and Infusion Rate by Age

  Age groups	BRINEURA dose administered every other week	Volume of BRINEURA solution	Infusion rate
  Birth to < 6 months	100 mg	3.3 mL	1.25 mL/hr
  6 months to < 1 year	150 mg	5 mL	2.5 mL/hr
  1 year to < 2 years	200 mg (first 4 doses)	6.7 mL (first 4 doses)	2.5 mL/hr
  	300 mg (subsequent doses)	10 mL (subsequent doses)
  2 years and older	300 mg	10 mL	2.5 mL/hr

  Missed Dose

  If one or more doses are missed, restart BRINEURA treatment as soon as possible, maintaining the 2-week interval between infusions thereafter.
  )
• See the full prescribing information for dosage modifications due to hypersensitivity reactions. (
  2.3 Administration Modifications due to Hypersensitivity Reactions Including Anaphylaxis

  In the event of a severe hypersensitivity reaction (e.g., anaphylaxis), immediately discontinue BRINEURA administration and initiate appropriate medical treatment. If the decision is made to readminister BRINEURA after the occurrence of anaphylaxis, initiate the subsequent infusion at approximately one-half the infusion rate at which the anaphylactic reaction occurred with appropriate premedication. For additional recommendations in the event of a hypersensitivity reaction,

  see Warnings and Precautions (5.1)

  .
  )
• See the full prescribing information for preparation and administration instructions. (
  2.4 Preparation Instructions for Intraventricular Administration of the Product

  BRINEURA and the Intraventricular Electrolytes must only be administered by the intraventricular route, using the provided Administration Kit for use with BRINEURA. Each vial of BRINEURA and Intraventricular Electrolytes is intended for a single dose only.

  BRINEURA is administered into the cerebrospinal fluid (CSF) by infusion via a surgically implanted reservoir and catheter (the "intraventricular access device system"). BRINEURA is intended to be administered via the Codman^®HOLTER RICKHAM Reservoirs (Part Numbers: 82-1625, 82-1621, 82-1616) with the Codman^®Ventricular Catheter (Part Number: 82-1650). The intraventricular access device reservoir and catheter must be implanted prior to the first infusion. It is recommended that the first dose be administered at least 5 to 7 days after device implantation.

  BRINEURA is intended to be administered with the B Braun Perfusor^®Space Infusion Pump System (Product Code: 8713030U). If an alternative pump must be used, the essential performance requirements for this syringe pump used to deliver BRINEURA are as follows:

  • Delivery rate of 1.25 or 2.5 mL per hr with delivery accuracy of +/- 1 mL per hr
  • Compatible with 20 mL syringes provided in the Administration Kit for use with BRINEURA
  • Occlusion alarm setting to ≤ 281 mm Hg
  • Cleared for intraventricular route of administration

  Administer BRINEURA and the Intraventricular Electrolytes using the provided Administration Kit for use with BRINEURA components

  [see How Supplied/Storage and Handling (16)]

  .

  Each infusion consists of 3.3 to 10 mL of BRINEURA followed by 2 mL of Intraventricular Electrolytes. The complete infusion must be administered using an infusion set with a 0.2 micron inline filter. The Intraventricular Electrolytes are used to flush the infusion line, port needle, and intraventricular access device in order to fully administer BRINEURA and to maintain patency of the intraventricular access device.

  Supplies for Infusion Preparation

  • BRINEURA and Intraventricular Electrolytes Injection vials (package 1 of 2)
    [see How Supplied/Storage and Handling (16)]
  • Administration Kit for use with BRINEURA (package 2 of 2)
    [see How Supplied/Storage and Handling (16)]
  • Syringe pump (not supplied)
  • Empty sterile single-use luer lock syringe, no larger than 3 mL (not supplied)

  Inspect the Administration Kit infusion components to ensure the components are in the individual packages and have not been compromised.

  Thaw BRINEURA and Intraventricular Electrolytes Injection vials at room temperature 20°C to 25°C (68°F to 77°F) for approximately 60 minutes.

  Do not

  thaw or warm vials any other way.

  Do not

  shake vials. Condensation will occur during thawing period.

  Do not

  re-freeze vials or freeze syringes containing BRINEURA or Intraventricular Electrolytes.

  Inspect fully thawed BRINEURA and Intraventricular Electrolytes Injection vials. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. BRINEURA is a clear to slightly opalescent and colorless to pale yellow solution. Intraventricular Electrolytes is a clear to colorless solution.

  Do not use

  if the solutions are discolored or if there is other foreign particulate matter in the solutions. BRINEURA vials may occasionally contain thin translucent fibers or opaque particles. These naturally occurring particles are cerliponase alfa. These particles are removed via the 0.2 micron inline filter without having a detectable effect on the purity or strength of BRINEURA. Intraventricular Electrolytes may contain particles, which appear during the thaw period; however, these dissolve when the solution reaches room temperature.
  ,
  2.6 Administration Instructions for Intraventricular Infusion

  Intraventricular Infusion of BRINEURA

  Figure 1 represents the intraventricular infusion system set up. Use aseptic technique during the infusion.
  
  Follow the steps below to proceed with the intraventricular infusion.

  Figure 1

  • 1.000000000000000e+00Use aseptic technique when preparing the BRINEURA syringe for infusion. Label one sterile syringe "BRINEURA" and attach the syringe needle.
  • 2.000000000000000e+00
    Confirm required dose and volume based on patient age per Table 1. Remove the green flip-off caps from one or both BRINEURA vials. Each BRINEURA vial contains 150 mg or 5 mL. Use the "BRINEURA" labeled syringe to withdraw the volume of BRINEURA solution from the vial per the required dose (see Table 1). Intermediate volumes that fall between 1 mL increments should be drawn up in the syringe to the nearest whole number, specifically 3.3 mL to 4 mL and 6.7 mL to 7 mL.

    Do not

    dilute BRINEURA.

    Do not

    mix BRINEURA with any other drug.
    
    Discard any unused portion left in the vial.
  • 3.000000000000000e+00Label the infusion line "intraventricular infusion only" (see Figure 1).
  • 4.000000000000000e+00Attach the syringe containing BRINEURA to the extension line (see Figure 2). Then connect the extension line to the infusion set with a 0.2 micron inline filter (see Figure 1).

    Figure 2

  • 5.000000000000000e+00Prime the infusion components with BRINEURA.
  • 6.000000000000000e+00Inspect scalp for signs of intraventricular access device reservoir leakage or failure and for potential infections
    [see Warnings and Precautions (5.2, 5.3)].
  • 7.000000000000000e+00Prepare the scalp for intraventricular infusion per institution standard of care.
  • 8.000000000000000e+00Insert port needle into intraventricular access device reservoir (see Figure 3).

    Figure 3

  • 9.000000000000000e+00Connect a separate empty sterile single-use luer lock syringe, no larger than 3 mL (not provided) to the port needle. Withdraw 0.5 mL to 1 mL of CSF to check patency of intraventricular access device (see Figure 4) and send specimen for culture.
    • Do not
      return CSF to intraventricular access device.
    • Routinely send CSF samples for infection monitoring
      [see Warnings and Precautions (5.2)].

    Figure 4

  • 1.000000000000000e+01Attach the infusion set with 0.2 micron inline filter to the port needle (see Figure 1).
    • Secure the components per institution standard of care.
  • 1.100000000000000e+01
    Place the syringe containing BRINEURA into the syringe pump and program the pump to deliver at an infusion rate of 1.25 or 2.5 mL per hour (Table 1).

    Set the pump volume limit to deliver the exact volume that corresponds to the dose of BRINEURA solution appropriate for the patient's age (Table 1).

    Set the occlusion alarm setting to alert at pressure ≤ 281 mm Hg. See syringe pump operating manual for details.

    Do not

    deliver as a bolus or manually.
  • 1.200000000000000e+01Administer pre-medication 30 to 60 minutes prior to the start of infusion
    .
  • 1.300000000000000e+01Monitor vital signs (blood pressure, heart rate) prior to the start of infusion, periodically during infusion, and post-infusion
    [see Warnings and Precautions (5.4)].
  • 1.400000000000000e+01
    Initiate infusion of BRINEURA at a rate of 1.25 or 2.5 mL per hour (Table 1).
  • 1.500000000000000e+01Periodically inspect the infusion system during the infusion for signs of leakage or delivery failure
    [see Warnings and Precautions (5.3)]
    .
  • 1.600000000000000e+01When the BRINEURA infusion is complete, detach and remove the syringe from the pump and disconnect from the tubing (see Figure 5). Discard the syringe containing any residual drug. Proceed to Step 16 for Intraventricular Electrolytes infusion.

    Figure 5

  

  

  

  

  

  Intraventricular Infusion of Intraventricular Electrolytes

  Administer the Intraventricular Electrolytes provided

  after

  BRINEURA infusion is complete.

  • 1.700000000000000e+01Use aseptic technique when preparing the Intraventricular Electrolytes syringe for infusion. Label one sterile syringe "Intraventricular Electrolytes" and attach the syringe needle. Remove the yellow flip-off cap from the Intraventricular Electrolytes Injection vial. Withdraw 2 mL of Intraventricular Electrolytes. Discard the remaining unused portion.
  • 1.800000000000000e+01Attach the syringe to the extension line (see Figure 6).

    Figure 6

  • 1.900000000000000e+01
    Place the syringe containing Intraventricular Electrolytes into the syringe pump and program pump to deliver at an infusion rate of 1.25 or 2.5 mL per hour (Table 1). Set the pump volume limit to deliver 2 mL. Set the occlusion alarm setting to alert at pressure ≤ 281 mm Hg. See syringe pump operating manual for details.

    Do not

    deliver as a bolus or manually.
  • 2.000000000000000e+01Initiate infusion of Intraventricular Electrolytes at a rate of 2.5 mL per hour.
  • 2.100000000000000e+01Periodically inspect the infusion system during the infusion for signs of leakage or delivery failure.
  • 2.200000000000000e+01When the Intraventricular Electrolytes infusion is complete, detach and remove the empty syringe from the pump and disconnect from the infusion line.
  • 2.300000000000000e+01Remove the port needle. Apply gentle pressure and bandage the infusion site per institution standard of care.

  Dispose of the infusion components, needles, unused solutions and other waste materials in accordance with local requirements.

  

  )

Injection: BRINEURA 150 mg/5 mL (30 mg/mL) solution, two single-dose vials per carton co-packaged with Intraventricular Electrolytes Injection 5 mL in a single-dose vial. BRINEURA is a clear to slightly opalescent and colorless to pale yellow solution. Intraventricular Electrolytes is a clear to colorless solution

There are no available data on BRINEURA use in pregnant women to inform a drug-associated risk of pregnancy-related outcomes. Animal reproduction studies have not been conducted using cerliponase alfa.

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 to 4% and 15 to 20%, respectively.