Abstract
Background:
L-glutamine (Endari ®) was approved by the US Food and Drug Administration (FDA) in July 2017 to reduce the acute complications of sickle cell disease (SCD) in adult and pediatric patients, aged 5 years and older. Data collected during the phase 2 and phase 3 trials demonstrated a rather mild adverse event profile at the approved doses (approximately 0.3 g/kg administered twice daily). The combined data from the clinical trials encompassed 187 patients assigned to the L-glutamine arm and 111 patients assigned to the placebo arm. The most common side effects observed were constipation, nausea, headache, abdominal pain, cough, pain in extremity, back pain, and chest pain. Since 2017, safety data for L-glutamine has been collected through several sources.
Aim:
To determine whether new safety concern signals for L-glutamine in the treatment of SCD have emerged over the post-marketing period since July of 2017.
Methods:
Individual case safety reports (ICSR) received from consumers, physicians, pharmacies, and other healthcare professionals that were processed in the global safety database in real time were reviewed. Continuous safety evaluations that were performed when evaluating ICSRs were collected. Additionally, signal management activities performed quarterly since July 2017, which included screening of literature and regulatory websites for the identification of potential safety information, were evaluated.
Results:
Overall, 1791 case reports were received with 2954 adverse events between July 07, 2017 (the date of approval) and July 06, 2021. A summary of frequently reported adverse events during the post-marketing phase is presented in Figure 1.
No new safety concerns have been identified upon evaluation of these events, which has been performed on a quarterly basis from the approval date.
Conclusion:
Post-marketing surveillance data indicates that L-glutamine administered at approximately 0.3 g/kg twice daily is safe and well-tolerated. The most common side effects observed during clinical trials were constipation, nausea, headache, abdominal pain, cough, pain in extremity, back pain, and chest pain (Table 1). These same side effects have been observed in the post-marketing phase with the exception of "cough." Side effects reported during the post-marketing phase that were not reported in the clinical trials were abdominal discomfort, diarrhea, malaise, and pain. The majority of these reports were categorized as non-serious (Figure 1). Information pertaining to these events was limited or the event could be explained by the underlying condition or concomitant medication; therefore, these events were not considered to be new safety concerns. In summary, there were no new safety concerns identified with L-glutamine for the treatment of SCD in the post-marketing period.
Figure 1 Figure 1.
Disclosures
Mayuzumi: Emmaus Medical, Inc: Current Employment. Razon: Emmaus Medical, Inc: Current Employment. Singh: Emmaus Medical, Inc: Current Employment. Goodrow: Emmaus Medical, Inc: Current Employment. Becerra: Emmaus Medical, Inc: Current Employment. Stark: Emmaus Medical, Inc: Current Employment. Niihara: Emmaus Lifesciences, Inc.: Current Employment.
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