Allergy to Macrogol 400 and Titanium Dioxide (E171) as Potential Triggers of Anaphylactic Reaction After Dydrogesterone Intake

ABSTRACT: The aim of this study was to determine the probable relationship between the development of an immediate anaphylactic reaction in a child and the presence of excipients-polyethylene glycol (PEG) 400 and titanium dioxide-in the composition of the drug dydrogesterone (Duphaston). The methodology includes a clinical case analysis that considers anamnestic data, pharmacological evaluation of drug composition, and comparison with relevant literature. The findings indicate that the patient had no allergic history and had previously tolerated medroxyprogesterone therapy without adverse effects. The reaction followed a typical course of immediate anaphylaxis characterized by generalized urticaria, angioedema, bronchospasm, tonic-clonic seizures, and hypotension. Complete resolution of symptoms was achieved after epinephrine administration and antishock therapy. A key distinction between the drugs was identified-the presence of PEG 400 and titanium dioxide exclusively in the formulation that triggered the reaction. These substances are capable of eliciting an immediate immune response even upon initial exposure, without a prior sensitization phase. The mechanism of the reaction is inconsistent with hypersensitivity to progestins, as the reaction occurred on first exposure, was systemic, and involved neurological manifestations. PEG 400 and titanium dioxide therefore have confirmed clinical immunotoxic significance and should be considered separately when evaluating drug reactions. The findings emphasize the importance of personalized drug selection that accounts for the immunoactive potential of excipients and support the inclusion of excipients in diagnostic algorithms for drug hypersensitivity.