Cerliponase alfa

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 ] .

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 ] . 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 ] . 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 ] .

Replace the intraventricular access device reservoir prior to 4 years of single-puncture administrations [see Warnings and Precautions ].

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 ].

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 1 for the appropriate volume and infusion rate. For volumes that are not whole numbers, see Dosage and Administration . [See table below.] 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.

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 .

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 ] .

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 ] Administration Kit for use with BRINEURA (package 2 of 2) [see How Supplied/Storage and Handling ] 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.

Storage Instructions for the Thawed Product and Product in Syringe Storage of Thawed Product Use thawed BRINEURA and Intraventricular Electrolytes immediately. If thawed BRINEURA and Intraventricular Electrolytes is not used immediately, store in the refrigerator at 2°C to 8°C (36°F to 46°F) for no more than 24 hours. Discard the thawed product after 24 hours if refrigerated.

Storage of Product in Syringe Use product held in labeled syringes immediately. If product held in labeled syringe is not used immediately, store in the refrigerator at 2°C to 8°C (36°F to 46°F) for no more than 4 hours prior to infusion. Discard the product held in labeled syringe after 4 hours if refrigerated.