Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intraventricular [preservative free]:
Brineura: 150 mg/5 mL (1 ea)
Pharmacology
Mechanism of Action
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.
Pharmacokinetics/Pharmacodynamics
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
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
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
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
Dosage and Administration
Dosing: Pediatric
Note: 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 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).
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 (serum: 79%; CSF: 33%)
Miscellaneous: Fever (71%)
1% to 10%:
Cardiovascular: Bradycardia (8%), hypotension (8%)
Central nervous system: Jitteriness (8%)
Local: Catheter infection (8%)
<1%, postmarketing, and/or case reports: Hypoxia, meningitis
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: 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 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, signs of infection, device leakage or failure (prior to infusion); routine CSF samples prior to each infusion and when clinically indicated (to detect subclinical device infections); 12-lead EKG every 6 months or during infusion with cardiac abnormalities.
Pregnancy
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, signs of meningitis (headache with fever, stiff neck, nausea, confusion, or sensitivity to light), abnormal heartbeat, fast heartbeat, slow heartbeat, 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.
