PEDIATRIC SAFETY
XENPOZYME safety profile in pediatric patients1
- 8 pediatric patients treated with XENPOZYME with a median exposure of 2.7 years were included in the pooled safety analysis from 3 clinical trials.
- Treatment-related serious adverse reactions, hypersensitivity reactions including anaphylaxis, and infusion-associated reactions (IARs) occurred within 24 hours of infusion and were observed in a higher percentage of pediatric patients than in adult patients.
- Serious adverse reactions of anaphylactic reaction were reported in 2 (25%) pediatric patients treated with XENPOZYME.
Adverse reactions occurring at >20% in XENPOZYME-treated pediatric patients with ASMD in the open-label pediatric trial* and a Long-Term Trial for an overall observation period of 2.5 to 3.2 years
Abdominal pain includes abdominal pain and abdominal pain upper. Fatigue includes fatigue and asthenia. Rash includes rash
and erythema.
*Duration of treatment in the open-label trial was 64 weeks. All patients continued into the Long-Term Trial.
ASMD=acid sphingomyelinase deficiency; IV=intravenous.
No patients in the pediatric trial permanently discontinued treatment due to treatment-related adverse events.2
XENPOZYME is an IV infusion.1
IMPORTANT SAFETY INFORMATION AND INDICATION
|
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.
Infusion-Associated Reactions
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.
ADVERSE REACTIONS
- 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.
INDICATION
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. XENPOZYME. Prescribing Information. 2. Data on file, Sanofi.
IMPORTANT SAFETY INFORMATION AND INDICATION
|
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.
Infusion-Associated Reactions
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.
ADVERSE REACTIONS
- 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.
INDICATION
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. XENPOZYME. Prescribing Information. 2. Data on file, Sanofi.