Premedication regimens

Premedication regimens of glucocorticoids and histamine Hi and H2 receptor antagonists have been used in an attempt to prevent hypersensitivity reactions in other phase 1 trials. These trials were successfully completed using infusion schedules of 1-120 hours and doses of 135-390 mg/m, with a lower incidence of hypersensitivity reactions (15,17,28,29,37,44,48). However, the use of premedication did not completely prevent such reactions. 

Table 95.4 Premedication regimens for patients at high risk or those with previous reactions to oontrast medium...

Premedication regimen for docetaxel oral dexamethasone 8 mg twice daily for 3 days starting 24 h prior to the commencement of infusion. For paclitaxel infused over 1, 3, and 24 h Hi antagonist diphenhydramine (50 mg) and an H2 antagonist (cimetidine 300 mg, ranitidine 50 mg, or famotidine 20 mg) given IV prior to infusion beginning. Oral dexamethasone 20 mg administered 12 and 6 h prior. 

Paclitaxel is metabolized by CYP2C8 and CYP3A4 [23, 83 ], and drugs that inhibit or induce these isoenzymes would be expected to alter the metabolism of paclitaxel. In vitro ranitidine, diphenhydramine, vincristine, vinblastine, and doxorubicin had little or no effect on the metabolism of paclitaxel, but barbiturates stimulated hydroxylation of the side-chain by induction of CYP3A isoforms [83 ]. Although cimeti-dine and famotidine have quite different CYP-modulating abilities, a clinical study showed no difference in paclitaxel clearance or associated neutropenia when cimetidine or famotidine were used as part of the premedication regimen [84 ]. 

Kloover JS, den Bakker MA, Gelderblom H, van Meerbeeck JP. Fatal outcome of a hypersensitivity reaction to paditaxel a critical review of premedication regimens. Br J Cancer 2004 90(2) 304-5. 

REF Cardenal et al. J Clin Oncol 1999 17 12-18 -there are multiple variants of this regimen PREMEDICATIONS... 

PJ is a 23-year-old man with ALL hospitalized for induction chemotherapy. He is scheduled to receive amphotericin B tonight as part of his prophylactic regimen against opportunistic infections. His premedications for amphotericin should include the following ... 

If testing is not possible, a premedication should be given. Unfortunately, currently there is no standard regimen, drugs given for premedication themselves can induce adverse drug reactions, and premedication does not guarantee absolute protection from hypersensitivity reaction after ICM reexposure [30]. 

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