Cremophor adverse reactions

At predose, if the vehicle contains an ingredient such as cremophor and Tween-80 that causes allergic reaction in animals, a pretreatment dosing regimen may be given to animals to minimize the chances for this reaction occur. At postdose, in the event that an adverse reaction is to occur, additional treatment may be followed as judged to be appropriate. 

In recent years, a Cremophor-free formulation of paclitaxel has been developed, with the trade name Abraxane. It uses nanoparticle albumin-bound (nab) technology as a vehicle for the delivery of paclitaxel. Abraxane is a Cremophor-free, 130-nanometer particle form of paclitaxel, which delivers paclitaxel as a suspension of albumin particles in saline. It therefore avoids the adverse reactions that are associated with Cremophor EL. It does not need premedication with glucocorticoids and antihistamines. In animals albumin-bound paclitaxel has increased and prolonged antitumor activity and more effective intratumor accumulation of paclitaxel, compared with Cremophor-based paclitaxel [93 ]. It is currently licensed for second-line treatment of metastatic breast cancer. 

Cremophor EL has been implicated in several cases of adverse reactions to the compound present as a solubilizer in intravenous anaesthetic preparations. Adverse reactions may be due to direct pharmacological release of histamine, to immune-mediated mechanisms, or to activation of C3 complement leading to release of histamine [121]. It has been variously estimated that the incidence of reactions to Althesin which contains 20 % Cremophor EL is 1 in 14 000 to 19 000, 1 in 900 or 1 in 1900 [122]. 

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 (11). 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... 

Topical miconazole is well tolerated. Parenteral administration carries a higher frequency of adverse effects, some probably being caused by Cremophor (polyethoxylated castor oil, the carrier). Adverse effects include fever, chills, pruritus, rash, nausea, vomiting, diarrhea, hjrpona-tremia, cardiac toxicity, phlebitis, hyperhpidemia, and central nervous system disturbances. Hypersensitivity reactions can occur. Tumor-inducing effects have not been reported. 

Phytomenadione given intravenously is generally tolerated well. However, intravenous administration of small amounts (2-5 mg) can be followed by severe short-lasting cyanosis, dyspnea, tachycardia, and low blood pressure in patients with cardiac failure. Flushing and sweating can occur. Anaphylactoid reactions may be due to the excipient Cremophor EL. The most important adverse effects are jaundice and kernicterus, which can occur in small and premature babies, even after small doses, probably because of immature liver function. 

---