Severe anaphylaxis following off-label rectal
use of injectable diazepam in a febrile seizure:
a case report and clinical implications

Severe anaphylaxis following off-label rectal
use of injectable diazepam in a febrile seizure:
a case report and clinical implications

Febrile seizure, Rectal diazepam, Propylene glycol, Pediatric anaphylaxis, Off-label use, Excipient
hypersensitivity, Emergency medicine,

Abstract
Background Off-label rectal administration of intravenous diazepam is commonly practiced for acute seizure
management in children when FDA-approved rectal gels (e.g., Diastat® AcuDial) are inaccessible—particularly in
low-resource settings like Vietnam. However, such injectable formulations often contain excipients not validated for
mucosal use, including propylene glycol and sodium benzoate, which may induce hypersensitivity reactions. Reports
of anaphylaxis in this context remain exceedingly rare.
Case presentation We describe a case of suspected grade III anaphylaxis in a 14-month-old girl with complex
febrile seizure who received 2 mg rectal diazepam (injectable formulation, Vidipha, Vietnam). Within five minutes of
administration, she developed generalized urticaria, apnea, cyanosis, and hypotonia. Emergency treatment included
intramuscular epinephrine, corticosteroids, antihistamines, and mechanical ventilation. She made a full recovery. The
diazepam preparation used contained approximately 40% propylene glycol and also included sodium benzoate—
both of which have been reported as potential triggers of non–IgE-mediated hypersensitivity reactions, particularly
when delivered via mucosal routes.
Conclusion This case underscores the potential for life-threatening adverse events following off-label rectal use of
injectable diazepam. Emergency clinicians should be aware of excipient-related risks and prioritize safer alternatives
such as intranasal midazolam. There is an urgent need for regulatory efforts to improve access to mucosal-safe,
pediatric-appropriate benzodiazepine preparations in resource-limited healthcare systems.
Keywords Febrile seizure, Rectal diazepam, Propylene glycol, Pediatric anaphylaxis, Off-label use, Excipient
hypersensitivity, Emergency medicine, Case report

Ninh Xuan Nguyen1*, Ngoc Tien Pham1

, Huong Thi Thanh Le1

, Quoc Viet Tran1

, Hang Ngoc Thuy Tran1
,

Thi Kim Thanh Vo1

and Chuong Thi Ngoc Dang2

https://doi.org/10.1186/s12245-026-01123-2

2026

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