Overview
11 DESCRIPTION Cerliponase alfa is a purified human enzyme produced by recombinant DNA technology in a Chinese hamster ovary cell line. The active substance is a recombinant human tripeptidyl peptidase-1 (rhTPP1), a lysosomal exopeptidase. The primary activity of the mature enzyme is the cleavage of N-terminal tripeptides from a broad range of protein substrates.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action CLN2 disease is a neurodegenerative disease caused by deficiency of the lysosomal enzyme tripeptidyl peptidase-1 (TPP1), which catabolizes polypeptides in the CNS. TPP1 has no known substrate specificity. Deficiency in TPP1 activity results in the accumulation of lysosomal storage materials normally metabolized by this enzyme in the central nervous system (CNS), leading to progressive decline in motor function. Cerliponase alfa (rhTTP1), a proenzyme, is taken up by target cells in the CNS and is translocated to the lysosomes through the Cation Independent Mannose-6-Phosphate Receptor (CI-MPR, also known as M6P/IGF2 receptor).
Indications
- 1 INDICATIONS AND USAGE BRINEURA is indicated to slow the loss of ambulation in pediatric patients with neuronal ceroid lipofuscinosis type 2 (CLN2 disease), also known as tripeptidyl peptidase 1 (TPP1) deficiency. BRINEURA is a hydrolytic lysosomal N-terminal tripeptidyl peptidase indicated to slow the loss of ambulation in pediatric patients with neuronal ceroid lipofuscinosis type 2 (CLN2 disease), also known as tripeptidyl peptidase 1 (TPP1) deficiency. ( 1 )
Common Doses
- 300 mg
- 100 mg
- 3.3 mL
- 1.25 mL
Dosage
2 DOSAGE AND ADMINISTRATION Administration of BRINEURA should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. ( 2.1 ) BRINEURA should be administered by or under the supervision of a physician experienced in intraventricular administration. ( 2.1 ) Premedication of patients with antihistamines with or without antipyretics or corticosteroids is recommended. ( 2.1 ) Prior to each infusion, inspect the scalp for signs of intraventricular access device reservoir leakage, failure, or potential infection. ( 2.
Black Box Warning
WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS Patients treated with enzyme replacement therapies have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. Initiate BRINEURA in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. If a severe hypersensitivity reaction (e.g.
Contraindications
- 4 CONTRAINDICATIONS BRINEURA is contraindicated in patients with: any sign or symptom of acute, unresolved localized infection on or around the device insertion site (e.g., cellulitis or abscess); or suspected or confirmed CNS infection (e.g., cloudy CSF or positive CSF gram stain, or meningitis) [see Warnings and Precautions (5.2) ] . any acute intraventricular access device-related complication (e.g., leakage, extravasation of fluid, or device failure) [see Warnings and Precautions (5.3) ]. ventriculoperitoneal shunts.
Side Effects
- 6 ADVERSE REACTIONS The following adverse reactions are described below and elsewhere in the labeling: Hypersensitivity Reactions Including Anaphylaxis [see Warnings and Precautions (5.1) ] Meningitis and Other Intraventricular Access Device-Related Infections [see Warnings and Precautions (5.2) ] Intraventricular Access Device-Related Complications [see Warnings and Precautions (5.3) ] Cardiovascular Adverse Reactions [see Warnings and Precautions (5.4) ] Infusion-Associated Reactions [see Warnings and Precautions (5.
Interactions
- No major interactions listed on the FDA label. Always consult a healthcare professional.