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Cerliponase Alfa

Medically reviewed by Drugs.com. Last updated on May 20, 2020.

Pronunciation

(ser LIP oh nase AL fa)

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)

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

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

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

Adverse reactions are reported from a small study population.

>10%:

Cardiovascular: ECG abnormality (71%)

Gastrointestinal: Vomiting (63%)

Hematologic & oncologic: Hematoma (21%)

Hypersensitivity: Hypersensitivity reaction (46%; reactions may not be consistent with classic immune mediated hypersensitivity)

Immunologic: Antibody development (serum: 79%; CSF: 33%)

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

Miscellaneous: Fever (71%)

1% to 10%:

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

Nervous system: Jitteriness (8%)

Respiratory: Hypoxia

Postmarketing: Hypersensitivity: Anaphylaxis

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 anaphylaxis, have been reported during and up to 24 hours after completion of cerliponase alfa infusion. Some patients also experienced pyrexia with vomiting, pleocytosis, or irritability. Pretreat with antihistamines with or without antipyretics or corticosteroids 30 to 60 minutes prior to start of infusion. Discontinue therapy immediately for severe hypersensitivity reactions or anaphylaxis and treat appropriately. 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 one-half the initial infusion rate at which anaphylactic reaction occurred.

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

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, 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.

Pregnancy Considerations

Animal reproduction studies have not been conducted with cerliponase alfa.

Patient Education

What is this drug used for?

• It is used to slow the loss of being able to walk around in some children.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• Meningitis like headache with fever, stiff neck, nausea, confusion, or sensitivity to light.

• Abnormal heartbeat

• Fast heartbeat

• Slow heartbeat

• Severe dizziness

• Passing out

• Seizures

• Irritability

• Anxiety

• Vomiting

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

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