WARNING: SEVERE HYPERSENSITIVITY REACTIONS
Hypersensitivity Reactions Including Anaphylaxis
Patients treated with XENPOZYME have experienced hypersensitivity reactions, including anaphylaxis. Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available during XENPOZYME administration. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, XENPOZYME should be discontinued immediately, and appropriate medical treatment should be initiated. In patients with severe hypersensitivity reaction, a desensitization procedure to XENPOZYME may be considered.
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions Including Anaphylaxis
See Boxed WARNING. Prior to XENPOZYME administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids.
- If a severe hypersensitivity reaction occurs, discontinue XENPOZYME immediately and initiate appropriate medical treatment. Consider the risks and benefits of re-administering XENPOZYME following severe hypersensitivity reactions.
- If a mild or moderate hypersensitivity reaction occurs, the infusion rate may be slowed or temporarily withheld, and/or the XENPOZYME dose reduced.
Antihistamines, antipyretics, and/or corticosteroids may be given prior to XENPOZYME administration to reduce the risk of infusion-associated reactions (IARs). However, IARs may still occur in patients after receiving pretreatment.
- If severe IARs occur, discontinue XENPOZYME immediately and initiate appropriate medical treatment. Consider the risks and benefits of re-administering XENPOZYME following severe IARs.
- If a mild or moderate IAR occurs, the infusion rate may be slowed or temporarily withheld, and/or the XENPOZYME dosage may be reduced.
An acute phase reaction (APR), an acute inflammatory response accompanied by elevations in inflammatory serum protein concentrations, was observed. Most of the APRs occurred at 48 hours post infusion during the dose escalation period. APRs can be managed as other IARs.
Elevated Transaminases Levels
XENPOZYME may be associated with elevated transaminases (ALT, AST, or both) within 24 to 48 hours after infusion. Levels generally returned to levels observed prior to the XENPOZYME infusion. To manage the risk of elevated transaminase levels, assess ALT and AST:
- within one month prior to initiation of XENPOZYME,
- within 72 hours prior to any infusion during dose escalation, which includes the first 3 mg/kg dose, or prior to the next scheduled XENPOZYME infusion upon resuming treatment following a missed dose.
Upon reaching the recommended maintenance dose, transaminase testing is recommended to be continued as part of routine clinical management of ASMD.
Risk of Fetal Malformations During Dosage Initiation or Escalation in Pregnancy
XENPOZYME 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. The decision to continue or discontinue XENPOZYME 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.
Verify pregnancy status in females of reproductive potential prior to initiating XENPOZYME treatment. Advise females of reproductive potential to use effective contraception during XENPOZYME treatment and for 14 days after the last dose if XENPOZYME is discontinued.
- Most frequently reported adverse drug reactions in adults (incidence ≥10%) were headache, cough, diarrhea, hypotension, and ocular hyperemia.
- Most frequently reported adverse drug reactions in pediatric patients (incidence ≥20%) were pyrexia, cough, diarrhea, rhinitis, abdominal pain, vomiting, headache, urticaria, nausea, rash, arthralgia, pruritus, fatigue, and pharyngitis.
XENPOZYME® (olipudase alfa-rpcp) is indicated for treatment of non–central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in adult and pediatric patients.
Please see full Prescribing Information, including Boxed WARNING, for complete details.
References: 1. McGovern MM, Avetisyan R, Sanson B-J, Lidove O. Disease manifestations and burden of illness in patients with acid sphingomyelinase deficiency (ASMD). Orphanet J Rare Dis. 2017;12(1):41. 2. McGovern MM, Dionisi-Vici C, Giugliani R, et al. Consensus recommendation for a diagnostic guideline for acid sphingomyelinase deficiency. Genet Med. 2017;19(9):967-974. 3. Cox GF, Clarke LA, Giugliani R, et al. Burden of illness in acid sphingomyelinase deficiency: a retrospective chart review of 100 patients. JIMD Rep. 2018;41:119-129. 4. Pulikottil-Jacob R, Munoz-Rojas MV, Gusto G, et al. Survival of patients with acid sphingomyelinase deficiency in the United States: a retrospective real-world study. Poster presented at: 2022 NORD Rare Diseases and Orphan Products Breakthrough Summit; October 17-18, 2022; Washington, DC.