Overview
11 DESCRIPTION Olipudase alfa-rpcp is a hydrolytic lysosomal sphingomyelin-specific enzyme consisting of 570 amino acids produced in a Chinese hamster ovary cell line by recombinant DNA technology. The molecular weight of olipudase alfa-rpcp is approximately 76 kDa. XENPOZYME (olipudase alfa-rpcp) for injection is supplied as a sterile, preservative-free, white to off-white lyophilized powder for...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action ASMD is a lysosomal storage disease that results from reduced activity of the enzyme acid sphingomyelinase (ASM), caused by pathogenic variants in the sphingomyelin phosphodiesterase 1 gene. ASM degrades sphingomyelin to ceramide and phosphocholine. The deficiency of ASM causes an intra-lysosomal accumulation of sphingomyelin (as well as cholesterol and other cell membrane lipids) in various tissues. XENPOZYME provides an exogenous source of ASM. XENPOZYME is not expected to cross the blood-brain barrier or modulate the CNS manifestations of ASMD. 12.2 Pharmacodynamics Plasma Ceramide Levels Ceramide is elevated in plasma of adult and pediatric patients with ASMD.
Indications
- 1 INDICATIONS AND USAGE XENPOZYME is indicated for treatment of non–central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in adult and pediatric patients. XENPOZYME is a hydrolytic lysosomal sphingomyelin-specific enzyme indicated for treatment of non–central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in adult and pediatric patients. ( 1 )
Common Doses
- 0.1 mg
- 0.03 mg
- 0.3 mg
- 0.6 mg
Dosage
2 DOSAGE AND ADMINISTRATION See Full Prescribing Information for important recommendations prior to XENPOZYME treatment initiation. ( 2.1 ) Adults: Recommended starting dose is 0.1 mg/kg administered as an intravenous infusion. ( 2.2 ) Pediatrics: Recommended starting dose is 0.03 mg/kg administered as an intravenous infusion. ( 2.3 ) See Full Prescribing Information for the recommended dose escalation and maintenance dosage, dosage modifications to reduce the risk of adverse reactions, and preparation and administration instructions. ( 2.2 , 2.3 , 2.5 , 2.6 , 2.7 ) 2.
Black Box Warning
WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS Patients treated with XENPOZYME have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Appropriate medical monitoring and support measures, including cardiopulmonary resuscitation equipment, should be readily available during XENPOZYME administration. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue XENPOZYME immediately and initiate appropriate medical treatment.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions Including Anaphylaxis [see Warnings and Precautions (5.1) ] Infusion-Associated Reactions (IARs) [see Warnings and Precautions (5.2) ] Elevated Transaminase Levels [see Warnings and Precautions (5.3) ] Most common adverse reactions in adult patients (incidence ≥10%) are headache, cough, diarrhea, hypotension, and ocular hyperemia. ( 6.
Interactions
- No major interactions listed on the FDA label. Always consult a healthcare professional.