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Cerliponase Alfa

Pronunciation

(ser LIP oh nase AL fa)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intraventric [preservative free]:

Brineura: 150 mg/5 mL (1 ea)

Brand Names: U.S.

  • Brineura

Pharmacologic Category

  • Hydrolytic Lysosomal N-terminal Tripeptidyl Peptidase

Pharmacology

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

VSS: CSF: 186 to 245 mL

Metabolism

Degraded via peptide hydrolysis

Time to Peak

CSF: 4.3 to 4.5 hours after start of infusion; Plasma: 12 to 12.3 hours after start of infusion

Half-Life Elimination

CSF: 6.2 to 7.7 hours

Use: Labeled Indications

Neuronal ceroid lipofuscinosis type 2: Delay the loss of ambulation in symptomatic pediatric patients ≥3 years of age with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2)

Contraindications

Acute intraventricular access device-related complications (eg, leakage, device failure, device-related infection); ventriculoperitoneal shunts

Dosing: Pediatric

Note: Administer the first dose 5 to 7 days after device implantation. Pretreat with antihistamines with or without antipyretics or corticosteroids 30 to 60 minutes prior to start of infusion.

Neuronal ceroid lipofuscinosis type 2: Children ≥3 years and Adolescents: Intraventricular: 300 mg (10 mL) once every other week; following cerliponase alfa infusion, administer 2 mL intraventricular electrolytes (included in administration kit)

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer's labeling.

Reconstitution

Thaw cerliponase alfa and intraventricular electrolyte vials at room temperature for approximately 60 minutes. Do not shake or refreeze vials; do not dilute cerliponase alfa or mix with any other drug. Cerliponase alfa may contain thin translucent fibers or opaque particles. Intraventricular electrolytes may contain particles, which appear during the thawing period but should dissolve when the solution reaches room temperature.

Administration

Intraventricular: For intraventricular use only; administer to the intraventricular space by infusion pump via a surgically-implanted reservoir and catheter. Infuse utilizing 0.2 micron inline filter (provided in kit) at a rate of 2.5 mL/hour; following cerliponase alfa dose, administer intraventricular electrolytes (included in administration kit) at the same rate. See prescribing information for details on intraventricular infusion.

Storage

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 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 Vials are single use only.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

>10%:

Cardiovascular: ECG abnormality (71%)

Central nervous system: Abnormal proteins in cerebrospinal fluid (decreased: 71%; increased: 21%), seizure (50%), abnormal cerebrospinal fluid (pleocytosis: 17%), headache (17%), irritability (17%)

Gastrointestinal: Vomiting (63%)

Hematologic & oncologic: Hematoma (21%)

Hypersensitivity: Hypersensitivity reaction (46%; not consistent with classic immune mediated hypersensitivity; included pyrexia with vomiting, pleocytosis, irritability)

Immunologic: Antibody development (33% to 79%)

Miscellaneous: Fever (71%)

1% to 10%:

Cardiovascular: Bradycardia (8%), hypotension (8%)

Central nervous system: Jitteriness (8%)

Local: Catheter infection (8%)

<1% (Limited to important or life-threatening): Hypoxia

Warnings/Precautions

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: Complications can occur with intraventricular access devices. Device-related infections have been reported with cerliponase alfa and may be subclinical. Administer using aseptic technique to minimize infection. Monitor access point skin integrity and send CSF samples routinely for signs of infection. Management of infection may include antibiotic treatment and device replacement before resumption of therapy. Monitor the device for signs of leakage or device failure. Material degradation of the intraventricular access device reservoir may occur with prolonged use (≥105 perforations), requiring replacement of the device.

• Hypersensitivity reactions: Hypersensitivity reactions, including pyrexia, vomiting, pleocytosis and irritability, have been reported in patients, during and up to 24 hours after completion of cerliponase alfa infusion. Pretreat with antihistamines with or without antipyretics or corticosteroids 30 to 60 minutes prior to start of infusion.

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.

Monitoring Parameters

Vital signs (blood pressure, heart rate) prior to start of infusion, periodically during infusion and post-infusion; skin integrity (prior to infusion); routine CSF samples (to detect subclinical device infections); 12-lead EKG every 6 months or during infusion with cardiac abnormalities.

Pregnancy Considerations

Animal reproduction studies have not been conducted with cerliponase alfa.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache. Have patient report immediately to prescriber signs of infection, abnormal heartbeat, tachycardia, bradycardia, severe dizziness, passing out, seizures, irritability, anxiety, or vomiting (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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