cerliponase alfa

ser-LIP-oh-nase AL-fa

Therapeutic Classification: none assigned

Pharmacologic Classification: enzymes

REMS

Neuronal ceroid lipofuscinosis type 2 (CLN2) (or tripeptidyl peptidase 1 [TPP1] deficiency).

Proenzyme is activated in the lysosomes and then cleaves tripeptides from a broad range of proteins. This leads to the breakdown of lysosomal storage materials that otherwise accumulate in patients with late infantile neuronal CLN2, leading to progressive decline in motor function.

Therapeutic effects:

Slowed decline in ambulation.

Absorption: Unknown.

Distribution: Distributed into CSF following intraventricular administration.

Metabolism/Excretion: Degraded through peptide hydrolysis.

Half-Life: 6.2–7.7 hr.

(CSF concentrations)

ROUTE	ONSET	PEAK	DURATION
Intraventricular	unknown	4.3–4.5 hr	unknown

Contraindicated in:

Acute infection around device insertion site or CNS infection;
Acute intraventricular access device-related complication;
Ventriculoperitoneal shunts.

Use Cautiously in:

Bradycardia, conduction disorder, or structural heart disease (↑ risk of conduction disorder or heart disease).

CV: ECG abnormalities, bradycardia, hypotension

GI: vomiting

Hemat: hematoma

Neuro: headache, irritability, pleocytosis, seizures, jitteriness, MENINGITIS

Misc: fever, hypersensitivity reactions (including anaphylaxis), infusion-associated reactions (including anaphylaxis), device-related complication (including device leakage, bulging of scalp around device, device failure), device-related infection

Drug-drug:

None reported.

Intraventricular(Children ≥2 yr): 300 mg every other wk. Follow each infusion with infusion of intraventricular electrolytes.
Intraventricular(Children 1–<2 yr): 200 mg every other wk for 1st four doses, then 300 mg every other wk. Follow each infusion with infusion of intraventricular electrolytes.
Intraventricular(Children 6 mo–<1 yr): 150 mg every other wk. Follow each infusion with infusion of intraventricular electrolytes.
Intraventricular(Children Birth–<6 mo): 100 mg every other wk. Follow each infusion with infusion of intraventricular electrolytes.

Solution for intraventricular infusion: 30 mg/mL (with 5-mL vial of intraventricular electrolyte solution for intraventricular infusion)

Obtain a sample of CSF for cell count and culture prior to each infusion and as clinically indicated.
Monitor BP and HR before infusion starts, periodically during infusion, and up to 8 hr postinfusion in a health care setting. On completion of infusion, clinically assess patient. Continue observation if clinically indicated.
Monitor ECG during infusion in patients with history of bradycardia, conduction disorder, or structural heart disease. Monitor regular 12-lead ECG every 6 mo in patients without cardiac abnormalities.
Assess scalp for signs of intraventricular access device leakage or failure (extravasation of CSF fluid, bulging of the scalp around or above intraventricular access device) or potential infection (erythema, tenderness, discharge, suspected or confirmed CNS infection) before each infusion. If signs occur, discontinue infusion.
Monitor for infusion-associated reactions (vomiting, seizure, rash, pyrexia, anaphylaxis) during and after infusion. If occurs, discontinue and immediately initiate appropriate medical treatment (epinephrine).
Monitor for signs and symptoms of hypersensitivity reactions (hypotension, generalized urticaria, dysphagia, dyspnea, flushing, chest discomfort, pruritus, nasal congestion) during and after infusion. Treatment depends on reaction severity; may include temporarily interrupting infusion and/or treatment with antihistamines, antipyretics, and/or corticosteroids. Consider the risks and benefits of readministering following severe hypersensitivity reactions.

Pretreat patients with antihistamines with or without antipyretics or corticosteroids 30–60 min before starting the infusion.
Administer in a health care setting by or under the direction of a health care professional knowledgeable in intraventricular administration; aseptic technique must be strictly observed during preparation and administration. Medical monitoring and supportive measures (cardiopulmonary resuscitation equipment, seizure precautions) available during administration.
Cerliponase alfa is infused into the CSF via a surgically implanted reservoir and catheter. 1st infusion is usually 5–7 days after device implantation. Replace the device reservoir before 4 yr of single-puncture administrations.
Intraventricular: Thaw cerliponase alfa and intraventricular electrolytes vials at room temperature for about 60 min. Do not thaw or warm any other way; do not shake vials. Condensation will occur during thawing period. Do not refreeze vials or freeze syringes containing cerliponase alfa or intraventricular electrolytes. Solution is clear to slightly opalescent and colorless to pale yellow; do not infuse solutions that are discolored, cloudy, or contain particulate matter. May occasionally contain thin translucent fibers or opaque particles removed by 0.2-micron filter. Infuse with the B Braun Perfusor Space Infusion Pump System. Solution can be stored in syringes in refrigerator for up to 4 hr before infusion, and vials can be stored in refrigerator for up to 24 hr. Use compatible 20-mL syringes provided in the administration kit. Do not dilute or mix with any other drug.
Rate: Infuse at 1.25 or 2.5 mL/hr with delivery accuracy of +/- 1 mL/hr through a 0.2-micron in-line filter. Set occlusion alarm setting to ≤281 mm Hg. Following the cerliponase alfa infusion, administer intraventricular electrolytes using the provided administration kit. Both infusions require a total of 2–4.5 hr. Intraventricular electrolytes are used to flush infusion line, port needle, and intraventricular access device to fully administer medication and maintain patency of intraventricular access device.

Explain purpose and side effects to patient and caregivers. Advise patient and caregivers to read Patient Information before starting therapy. If one or more doses are missed, restart treatment as soon as possible; maintain the 2 wk interval between infusions.
Advise patient and caregivers to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Instruct patient and caregivers to notify health care professional immediately if signs and symptoms of infection, hypotension, bradycardia, infusion-associated reactions, and hypersensitivity reactions occur.
Advise patients and caregivers of the risk of device-related infections. If any signs of infection are present, instruct to immediately contact a health care provider.

Slowed decline in ambulation.

Brineura

NDC Code

68135- BioMarin Pharmaceutical Inc.
- 68135-502-
  - 68135-502-00- 2000 mL in 1 BOTTLE (68135-502-00)

68135- BioMarin Pharmaceutical Inc.
- 68135-811- Brineura
  - 68135-811-02- 1 KIT in 1 CARTON (68135-811-02) * 5 mL in 1 VIAL, GLASS (68135-500-00) * 5 mL in 1 VIAL, GLASS (68135-495-04)

71931- BioMarin International Limited
- 71931-820-
  - 71931-820-99- 2000 mL in 1 BOTTLE (71931-820-99)

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