D3.259 - KOLLIPHOR : An excipient to be futher explored
Case report
Background :
KOLLIPHOR EL (formerly known as CREMOPHOR), chemically known as Ethoxylated Hydrogenated Castor Oil or macrogolglycerol ricinoleate, is a surfactant derived from castor oil, used in the pharmaceutical industry as an emulsifier. Many publications relate an imputability of this excipient in hypersensitivity reactions.
Case report :
We report the case of a 21 year old patient, referred to our departement for a grade 3 anaphylaxis (facial erythema, dyspnea, loss of consciousness) according to Ring and Messmer classification, after a first intraveinous (IV) administration of CYCLOSPORINE containing KOLLIPHOR, as part of the treatment of an ulcerative colitis. We note the absence of premedication. Percritical tryptase has not been dosed.
Skin prick tests were carried out to KOLLIPHOR (sample kindly provided by BASF laboratories), after placing a safety IV cathether, at the concentration of 1/10th then to the pure form and to CYCLOSPORINE (IV form containing KOLLIPHOR) at the concentration of 1mg/mL, and were all negative. Intradermal tests (IDT) were then performed to CYCLOSPORINE (0.1 mg/mL then 1 mg/mL) and were negative. Afterwards, a provocation test was performed to the oral form of CYCLOSPORINE, containing as well KOLLIPHOR, up to a total dose of 150 mg, and was well tolerated. Allergy work-up to Latex and Chlorhexidine was negative (skin tests and specific IgEs). The baseline tryptase is 6.8µg/L.
Discussion:
Several physiopathological mechanisms of adverse reactions to KOLLIPHOR have been described. Non-IgE reactions were evoked, by mast cell or complement non-specific activation, which is probably the case of our patient. A re-exposure with reinforced premedication and reduction of perfusion rate often leads to tolerance. However, IgE mediated reactions were reported in literature with positive allergy workup to KOLLIPHOR (prick tests and basophil activation test).
Conclusion:
KOLLIPHOR is an excipient that can be responsible for IgE or non IgE mediated hypersensitivity reactions. A complete allergy work-up is essential consisting of skin prick tests to KOLLIPHOR and percritical tryptase dosage, which can help define the underlying mecanism and thus, set the indication of KOLLIPHOR eviction, found in multiple treatments (CYCLOSPORINE, PACLITAXEL, VITAMINS ..).
