Version July 2025
Patients treated with enzyme replacement therapies have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement and after extended duration of therapy. Initiate cerliponase alfa in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. If a severe hypersensitivity reaction (eg, anaphylaxis) occurs, discontinue cerliponase alfa and immediately initiate appropriate medical treatment, including use of epinephrine. Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur.
Dosage guidance:
Safety: Premedicate with antihistamines with or without antipyretics or corticosteroids 30 to 60 minutes prior to start of infusion.
Neuronal ceroid lipofuscinosis type 2: Neonates: PMA ≥37 weeks and weighing ≥2.5 kg: Intraventricular: 100 mg once every other week via implanted reservoir and infusion device specific for cerliponase alfa; begin therapy (first dose) 5 to 7 days after device implantation. Following cerliponase alfa infusion, administer 2 mL intraventricular electrolytes (included in administration kit).
Dosing: Altered Kidney Function: Neonatal: There are no dosage adjustments provided in the manufacturer's labeling.
Dosing: Altered Liver Function: Neonatal: There are no dosage adjustments provided in the manufacturer's labeling.
Note: Premedicate with antihistamines with or without antipyretics or corticosteroids 30 to 60 minutes prior to start of infusion.
Neuronal ceroid lipofuscinosis type 2:
Infants weighing ≥2.5 kg, Children, and Adolescents: Intraventricular: Dose based on age (see table); administer once every other week infused via implanted reservoir and infusion device specific for cerliponase alfa; begin therapy (first dose) 5 to 7 days after device implantation. Following cerliponase alfa infusion, administer 2 mL intraventricular electrolytes (included in administration kit).
|
Age |
Initial 4 doses every other week |
Subsequent doses every other week |
|---|---|---|
|
<6 months |
100 mg |
100 mg |
|
6 months to <1 year |
150 mg |
150 mg |
|
1 year to <2 years |
200 mg |
300 mg |
|
≥2 years |
300 mg |
300 mg |
Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling.
Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in children.
>10%:
Cardiovascular: ECG abnormality
Gastrointestinal: Vomiting
Hematologic & oncologic: Hematoma
Hypersensitivity: Hypersensitivity reaction (reactions may not be consistent with classic immune-mediated hypersensitivity), infusion-related reaction
Immunologic: Antibody development (including neutralizing antibodies)
Nervous system: Abnormal cerebrospinal fluid (pleocytosis), abnormal proteins in cerebrospinal fluid (increased or decreased), headache, irritability, seizure
Miscellaneous: Fever
1% to 10%:
Cardiovascular: Bradycardia, hypotension
Nervous system: Jitteriness
Respiratory: Hypoxia
Postmarketing: Hypersensitivity: Anaphylaxis
Sign or symptom of acute, unresolved localized infection on or around device insertion site (eg, cellulitis, abscess); suspected or confirmed CNS infection (eg, meningitis, cloudy CSF or positive CSF gram stain); acute intraventricular access device-related complications (eg, leakage, extravasation of fluid, device failure); ventriculoperitoneal shunts
Canadian labeling: Additional contraindications (not in US labeling): Severe hypersensitivity to cerliponase or any component of the formulation
Concerns related to adverse effects:
• Cardiovascular adverse reactions: Hypotension has been reported up to 8 hours after the completion of cerliponase alfa infusion; monitor vital signs. Use with caution in patients with a history of bradycardia, conduction disorder, or structural heart disease; monitor EKG during infusion.
• Device-related complications: Device-related complications, including device leakage and failure, extravasation of CSF fluid, and bulging of the scalp near the intraventricular access device, have been reported with cerliponase alfa. Monitor the device for signs of leakage or device failure. Discontinue use of cerliponase alfa and refer to device manufacturer's labeling if device-related complications occur. Material degradation of the intraventricular access device reservoir may occur with prolonged use; the device should be replaced prior to 4 years of single-puncture administrations (approximately 105 perforations).
• Device-related infections: Device-related infections, including bacterial meningitis and other infections requiring antibiotic treatment and device removal, have been reported with cerliponase alfa. In reported cases, patients were able to resume treatment after administration of antibiotics and removal and replacement of the intraventricular access device. Obtain a CSF sample for cell count and culture prior to each infusion and when clinically indicated; patients with CLN2 disease may not display signs and symptoms of infection. Monitor device insertion site for signs of infection. Use is contraindicated with signs of localized infection (eg, erythema, tenderness, discharge) on or near the device insertion site or suspected or confirmed CNS infection (eg, meningitis, cloudy CSF or positive CSF gram stain).
• Hypersensitivity reactions: Hypersensitivity reactions, including anaphylaxis, have been reported upon initiation of enzyme therapy and also later in the course of therapy. Hypersensitivity reactions were reported more frequently in patients <3 years of age and have included anaphylaxis. Reactions have occurred during and up to 24 hours after completion of cerliponase alfa infusion. Initial therapy should be administered in a health care setting that includes cardiopulmonary monitoring and can provide resuscitation if necessary. Some patients also experienced pyrexia with vomiting, pleocytosis, or irritability. If the decision is made to readminister after anaphylaxis, appropriately trained personnel and emergency medications should be immediately available.
• Infusion-related reactions: Cerliponase alfa may cause infusion-related reactions, including fever, rash, seizure, and vomiting.
Other warnings/precautions:
• Appropriate use: Administer cerliponase alfa by FDA-approved infusion pump system via intraventricular implanted catheter access (consult prescribing information for device details); health care providers should be experienced with intraventricular drug administration.
Administration in patients PMA <37 weeks or weighing <2.5 kg is not recommended as physiologic immaturity may increase the risk of hypersensitivity reactions as well as serious, clinically significant adverse effects.
An extension study (5 years exposure) of the primary multicenter, open-label dose-escalation study (n=23, age range: 3.1 to 8.9 years) reported that 100% of subjects had ≥1 adverse event; most common adverse effects were hypersensitivity-type reactions and complications related to the indwelling intracerebroventricular device (necessitating device removal, anti-infective treatment, and subsequent device replacement); however, no adverse events led to dose reduction, study discontinuation, or death (Schulz 2024).
Higher titers of anti-drug antibodies (ADAs) in serum and cerebrospinal fluid have been reported in patients <3 years of age compared to patients ≥3 years; the clinical significance and safety implications of these are not defined. A multicenter, open-label dose-escalation study (n=23, age range: 3.1 to 8.9 years) reported that ADA status did not correspond to the likelihood or severity of hypersensitivity adverse events (Cherukuri 2018).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intraventricular [preservative free]:
Brineura: 150 mg/5 mL (1 ea)
No
Kit (Brineura Intraventricular)
2 X 150 mg/5 mL (per each): $41,704.80
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Kit, Intraventricular:
Brineura: 2 X 150 MG/5ML
Note: Premedicate with antihistamines with or without antipyretics or corticosteroids 30 to 60 minutes prior to infusion. Monitor patients closely for infusion-related or hypersensitivity reactions. Initiate therapy in a health care setting that includes cardiopulmonary monitoring and can provide resuscitation if necessary.
Intraventricular: For intraventricular use only; administer to the intraventricular space by infusion pump via a surgically implanted reservoir and catheter (see manufacturer labeling for specific product codes of reservoir, catheter, and infusion pump system required for cerliponase alfa administration). Inspect scalp prior to each infusion for leakage or failure of intraventricular access device or signs of infection. Use a 0.2 micron inline filter (provided in kit); after completion of dose, administer intraventricular electrolytes (2 mL volume, included in administration kit) at 2.5 mL/hour; total infusion time (combined drug and electrolyte infusions) is approximately 3.5 to 4.5 hours. See manufacturer labeling for details on intraventricular infusion.
|
Age |
Dose |
Dose volume |
Infusion rate |
Minimum total infusion time |
|---|---|---|---|---|
|
a Infusion times adapted from dose volumes and infusion rates presented in manufacturer labeling. | ||||
|
Birth to <6 months |
100 mg |
3.3 mL |
1.25 mL/hour |
2.7 hours |
|
6 months to <1 year |
150 mg |
5 mL |
2.5 mL/hour |
2 hours |
|
1 year to <2 years, initial doses |
200 mg |
6.7 mL |
2.5 mL/hour |
2.7 hours |
|
1 year to <2 years, subsequent doses |
300 mg |
10 mL |
2.5 mL/hour |
4 hours |
|
≥2 years |
300 mg |
10 mL |
2.5 mL/hour |
4 hours |
Rate adjustment for infusion-related reactions or hypersensitivity:
Mild to moderate hypersensitivity or moderate infusion-related reactions: Treatment of hypersensitivity reactions should be based on the severity of the reaction and may include temporarily interrupting the infusion and/or antihistamines, antipyretics, and/or corticosteroids. If the decision is made to readminister after anaphylaxis, appropriately trained personnel and emergency medications should be immediately available; initiate subsequent infusion at approximately 1/2 the initial infusion rate at which anaphylactic reaction occurred.
Anaphylaxis or severe hypersensitivity or infusion-related reaction: Discontinue therapy immediately for severe hypersensitivity reactions or anaphylaxis and treat appropriately.
Missed doses: If one or more doses are missed, restart therapy as soon as possible, maintaining the 2-week dosing interval.
Store cerliponase alfa injection and intraventricular electrolytes injection upright in a freezer at -25°C to -15°C (-13°F to 5°F) in original carton and protect from light. Store administration kit in original carton separately from cerliponase alfa. Do not freeze kit. Thaw cerliponase alfa and intraventricular electrolytes vials at room temperature for approximately 60 minutes. Preferably, administer immediately after thawing. May store thawed vials at 2°C to 8°C (36°F to 46°F) for up to 24 hours; discard after 24 hours. Use product held in labeled syringes immediately. If not used immediately, store in syringes at 2°C to 8°C (36°F to 46°F) and use within 4 hours; discard after 4 hours. Vials are single use only.
To delay the loss of ambulation in symptomatic patients with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2, or tripeptidyl peptidase 1 [TPP1] deficiency) (FDA approved in pediatric patients starting at birth).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
There are no known significant interactions.
Animal reproduction studies have not been conducted with cerliponase alfa.
Symptoms of anaphylaxis and hypersensitivity reactions (during infusion and within 24 hours following infusion); vital signs (blood pressure, heart rate) prior to start of infusion and periodically during infusion and postinfusion; skin integrity and signs of infection, device leakage or failure (prior to infusion); routine cerebrospinal fluid samples prior to each infusion and when clinically indicated (to detect subclinical device infections); in patients with cardiac abnormalities, ECG during infusion, and every 6 months in patients without cardiac abnormalities.
Cerliponase alfa is a proenzyme that, once activated, cleaves tripeptides from the N-terminus of proteins. This leads to the breakdown of lysosomal storage materials that otherwise accumulate in patients with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), leading to progressive decline in motor function.
Intraventricular electrolytes (included in the administration kit) are used to flush the infusion line, port needle, and intraventricular access device in order to fully administer cerliponase alfa and maintain patency of the intraventricular access device.
Distribution: Pediatric patients ≥3 years: VSS: CSF: Median range: 186 to 245 mL; with repeat dosing, volume was observed to decrease
Metabolism: Degraded via peptide hydrolysis
Half-life elimination: CSF: 6.2 to 7.7 hours
Time to peak: Pediatric patients ≥3 years: CSF: Median range: 4.3 to 4.5 hours after start of infusion; Plasma: Median range: 12 to 12.3 hours after start of infusion
Pediatric: When administered at therapeutic doses, the cerebrospinal fluid (CSF) Cmax and AUC0-t in patients <3 years of age was lower compared to patients ≥3 years of age, whereas plasma Cmax and AUC0-t was elevated. The clinical significance of higher systemic exposure (ie, lower CSF:plasma Cmax and CSF:plasma AUC0-t) in patients <3 years of age is undefined in terms of efficacy or safety.
