Peringatan Keamanan

Based on findings from animal reproduction studies, XENPOZYME may cause embryo-fetal harm when administered to a pregnant female. olipudase alfa-rpcp dosage initiation or escalation, at any time during pregnancy, is not recommended as it may lead to elevated sphingomyelin metabolite levels that may increase the risk of fetal malformations. However, the decision to continue or discontinue olipudase alfa-rpcp maintenance dosing in pregnancy should consider the female’s need for XENPOZYME, the potential drug-related risks to the fetus, and the potential adverse outcomes from untreated maternal ASMD disease.L49146

In an embryo-fetal toxicity study in pregnant mice, a rare malformation (exencephaly) was observed in offspring at an exposure less than the exposure at the maximum recommended human dose (MRHD) of olipudase alfa-rpcp. There are no available data on olipudase alfa-rpcp use in pregnant females to evaluate for a drug associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Advise the pregnant female of the potential risk to the fetus.L49146

Cases of overdosage with XENPOZYME have been reported in pediatric patients during dose escalation. Some patients experienced serious adverse reactions including death within 24 hours
of initial dose. The clinical findings included fever, hypotension, gastrointestinal bleeding, marked elevation in liver tests, metabolic acidosis, respiratory failure, and vomiting. There is no known specific antidote for olipudase alfa-rpcp overdosage. In the event of overdosage, immediately stop the infusion, and monitor the patient closely in a hospital setting for the development of hypersensitivity reactions and IARs including acute phase reactions.L49146

Studies to evaluate the carcinogenic potential of olipudase alfa-rpcp have not been conducted.L49146

Studies to evaluate the mutagenic potential of olipudase alfa-rpcp have not been conducted.L49146

Intravenous administration of olipudase alfa-rpcp every other day at doses up to 30 mg/kg had no adverse effects in a combined study of fertility in male and female mice. Exposures at this dose, based on the embryo-fetal development study, were estimated to be approximately 1.5-fold those of the MRHD of olipudase alfa-rpcp.L49146

Olipudase alfa

DB12835

biotech approved investigational

Deskripsi

Olipudase alfa is recombinant human acid sphingomyelinase.A251590 It is the first and only enzyme replacement therapy in the world for the treatment of Acid Sphingomyelinase Deficiency (ASMD), also known as Niemann–Pick disease.L42740 ASMD is a rare lysosomal storage disease caused by mutations in the SMPD1 gene, leading to a deficiency in acid sphingomyelinase and the abnormal accumulation of the primary ASM substrate, sphingomyelin.A251600 Olipudase alfa works to hydrolyze sphingomyelin accumulated in body tissues, such as the lungs, liver, spleen, kidneys, and bone marrow.A251590

Olipudase alfa gained its first global approval in Japan on March 28, 2022.A251590 It was later approved by the European Commission on June 28, 2022 L42740 and by the FDA on August 31, 2022.L43145

Struktur Molekul 2D

Struktur tidak tersedia

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) After administration of 3 mg/kg olipudase alfa once every two weeks in adults with ASMD, the mean terminal half-life (t1/2) ranged from 31.9 to 37.6 hours.[L42735]
Volume Distribusi After administration of 3 mg/kg olipudase alfa once every two weeks in adults with ASMD, the estimated mean (CV%) volume of distribution of olipudase alfa is 13.1 L (18%). Olipudase alfa is not expected to cross the blood-brain barrier or modulate the CNS manifestations of the disease.[L42735]
Klirens (Clearance) After administration of 3 mg/kg olipudase alfa once every two weeks in adults with ASMD, the mean (CV%) clearance of olipudase alfa is 0.331 L/h (22%).[L42735]

Absorpsi

In adult patients with ASMD, the mean (SD) maximum plasma olipudase alfa-rpcp concentration (Cmax) and area under the concentration-time curve (AUC) at steady state were 30 (5) mcg/mL and 607 (120) mcg?h/mL, respectively, at the recommended maintenance dose of 3 mg/kg administered once every 2 weeks. Olipudase alfa-rpcp Cmax and AUC increase proportionally over a dose range of 0.1 to 3 mg/kg (0.03 to 1 times the approved recommended maintenance dose).L49146

Metabolisme

Olipudase alfa is a recombinant human enzyme and is expected to be eliminated via proteolytic degradation into small peptides and amino acids.L42735

Rute Eliminasi

There is no information available.

Interaksi Obat

0 Data
Tidak ada data.

Referensi & Sumber

Artikel (PubMed)
  • PMID: 35639287
    Keam SJ: Olipudase Alfa: First Approval. Drugs. 2022 Jun;82(8):941-947. doi: 10.1007/s40265-022-01727-x.
  • PMID: 20301544
    Wasserstein MP, Schuchman EH: Acid Sphingomyelinase Deficiency .
  • PMID: 28228103
    McGovern MM, Avetisyan R, Sanson BJ, Lidove O: Disease manifestations and burden of illness in patients with acid sphingomyelinase deficiency (ASMD). Orphanet J Rare Dis. 2017 Feb 23;12(1):41. doi: 10.1186/s13023-017-0572-x.
  • PMID: 33875845
    Diaz GA, Jones SA, Scarpa M, Mengel KE, Giugliani R, Guffon N, Batsu I, Fraser PA, Li J, Zhang Q, Ortemann-Renon C: One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency. Genet Med. 2021 Aug;23(8):1543-1550. doi: 10.1038/s41436-021-01156-3. Epub 2021 Apr 19.

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Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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