Taxane hypersensitivity premedication

On the basis of an in vitro study using human liver sliees and human liver mierosomes it has been coneluded that the metabolism of paclitaxel is unlikely to be altered by cimetidine, dexamethasone or diphenhydramine, all of which are frequently given to prevent the hypersensitivity reactions associated with paclitaxel or its vehicle, Cremophor (see b, below). The UK manufacturers say that paclitaxel clearance in patients is not affected by cimetidine premedication, although some authors have advised caution when using cimetidine with docetaxel or paclitaxel since cimetidine is known to affect the cytochrome P450 isoenzyme CYP3A4, which is responsible, in part, for the metabolism of these taxanes. 

Paclitaxel Taxane (Diterpene) Breast, ovarian, head and neck, lung, bladder, etc. Inhibition mitotic cell division Acral erythema injection site reaction AGEP-Uke EM SJS Neutre nia hypersensitivity pn GI synptoms back pain Dys Incidence 10-16 % without premedication. Risks—atopy, bee sting allergy... 

The Castells group treated 17 consecutive patients with hypersensitivity to taxanes using a standard 6-7 h desensitization protocol. The patients underwent a total of 77 rapid desensitizations to docetaxel or pachtexal. Seventy two of the procedures were tolerated without reactions, four patients responded with hypersensitivity reactions that were milder than their initial reactions, and these patients toleratedre-administration of infusions. Five patients rechallenged before desensitization experienced recurrent reactions even though they were given additional premedication, and the infusion rate was reduced. 

In phase 1 studies, sagopilone has a similar adverse reactions profile to those of taxanes and ixabepilone neuropathy and neutropenia are the most commonly reported adverse events [16 ]. Motor neuropathy has not been reported so far, although in one phase I study, two patients reported symptoms of central ataxia [164=]. Diarrhea is less common with sagopilone than with ixabepilone and patupilone. Premedication is not routinely given with sagopilone and hypersensitivity reactions have not been reported so far. 

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