Cremophor

General information

Cremophor is a non-ionic solubilizer and emulsifier that is made by reacting ethylene oxide with castor oil [ ]. It is a pale yellow oily liquid consisting of a mixture of components, primarily polyethylene glycol conjugates. Fatty acid esters of polyethyleneglycol are also present, as well as hydrophilic polyethylene glycols and ethoxylated glycerol. It is present in intravenous formulations of the anticancer drugs teniposide and paclitaxel. The paclitaxel formulation consists of 6 mg/ml in 50% ethanol and 50% Cremophor. Thus, a patient receiving paclitaxel in the widely used dose of 175 mg/m ² will also receive about 14 ml/m ² of Cremophor.

Non-IgE-mediated anaphylactic (anaphylactoid) reactions can occur after the intravenous administration of Cremophor [ ] when it is used as a diluent of alfadolone/alfaxolone [ ], ciclosporin [ ], paclitaxel [ ], propanidid [ , ], teniposide [ ], and vitamin K [ , ]. Cardiorespiratory arrest after intravenous miconazole has been attributed to the histamine-releasing properties of Cremophor [ ].

In a study of the effects of Cremophor after 74 cycles of doxorubicin in Cremophor in 39 patients, there were no major hypersensitivity reactions to Cremophor, and no patients had their infusion discontinued or modified [ ]. Adverse effects that were considered to be potentially related to Cremophor were cutaneous (pruritus, flushing, or rashes), hypotension or dizziness, and headache. Because of the subjective nature of some of these symptoms, they were classified as grade 1 (mild and not requiring treatment or interfering with function), grade 2(moderate, causing some impairment of function but not requiring hospitalization), or grade 3 (severe, requiring hospitalization or causing significant interference with function). No grade 2 or 3 toxicity was recorded at the first three doses. One patient at level 4A had grade 2 dizziness, one patient at level 5 had grade 2 rash, one patient at level 5 had grade 3 headache and grade 3 pruritus, and one patient at level 6 had grade 3 hypotension and grade 3 rash. In no patient did these symptoms occur with doxorubicin alone, confirming their relation to Cremophor. These symptoms began several hours to days after Cremophor and persisted for 1–2 weeks, with the exception of the patient at level 5, whose pruritus gradually resolved over 3 months after discontinuing Cremophor.