Paclitaxel hypersensitivity docetaxel

The combination regimen of paclitaxel (or docetaxel) and carbo-platin frequently is responsible for producing hypersensitivity reactions. Each agent precipitates a distinct reaction, allowing for differentiation between causative factors. Hypersensitivity reactions have been observed with paclitaxel and docetaxel as frequently as 34% of... 

Adverse effects of paclitaxel and docetaxel are similar, being hypersensitivity reactions, bone marrow suppression, peripheral neuropathy, hair loss and cardiac arrhythmias. 

Both drugs are highly lipid soluble and as such are prepared and administered in dilutants (paclitaxel in Cremophor EL and docetaxel in polysorbate 80). Both medications are normally administered with dexamethasone, H, and H2 antagonists as premedications to decrease the incidence of the acute hypersensitivity reaction (HSR) (dyspnea with bronchospasm, urticaria, and hypotension) that has been observed to occur... 

Paclitaxel has very limited solubility and must be administered in a vehicle of 50% ethanol and 50% polyethoxylated castor oil (CREMOPHOR EL), a formation likely responsible for a high rate of hypersensitivity reactions. Patients receiving this formulation are protected by pretreatment with a histamine Hj receptor antagonist such as diphenhydramine, an receptor antagonist such as cimetidine fsee Chapter 24), and a glucocorticoid such as dexamethasone (see Chapter 59). Docetaxel, which is somewhat more soluble, is administered in polysorbate 80 and causes a lower incidence of hypersensitivity reactions. Pretreatment with dexamethasone is required to prevent progressive, and often disabling, fluid retention. 

Toxicity Paclitaxel causes neutropenia, thrombocytopenia, a high incidence of peripheral neuropathy, and possible hypersensitivity reactions during infusion. Docetaxel causes neurotoxicity and bone marrow depression. 

Low water solubility is a significant drawback to the therapeutic utility of the taxanes. This is particularly true of paclitaxel, which has a more lipophilic acetate moiety at Cio compared to docetaxel s more polar hydroxyl group. Paclitaxel must be administered in a vehicle of 50% alcohol/50% polyoxyethylated caster oil, which can lead to an enhanced risk of hypersensitivity reactions (dyspnea, hypotension, angioedema, and uticaria)... 

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. 

Taxanes such as docetaxel and paclitaxel are mitotic inhibitors, disrupting microtubule function so adverse reactions, including hypersensitivity responses, to these drugs might be expected. 

Patients with severe hypersensitivity to paclitaxel also react to docetaxel, giving a crosssensitivity rate of 90 %. 

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