Paclitaxel Diphenhydramine

Paclitaxel Peripheral neuropathy (DLT), nausea/vomiting, alopecia, hypersensitivity reactions Use caution with any elevation in AST (SGOT). Give proper dosing for liver dysfunction. Premedicate dexamethasone, diphenhydramine, and cimetidine. 

Premedication, consisting of dexamethasone 20 mg intravenously, 12 and 6 hours before the infusion, and diphenhydramine 50 mg and cimetidine 300 mg, intravenously 30 minutes before the infusion, are now routinely given before patients are treated with paclitaxel, and this, as well as a recommended infusion time of 3 hours, has reduced the incidence and severity of hypersensitivity reactions. A single dose of dexamethasone 16 mg given 30 minutes before paclitaxel was effective in preventing hypersensitivity reactions in 43 patients (38) however, whether a single dose of a glucocorticoid is sufficient for prophylaxis is controversial. 

Paclitaxel is metabolized by the cytochrome P450 isoenzymes CYP2C and CYP3A4 (53), and drugs that inhibit or induce these isozymes 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... 

C It is recommended that all patients receiving paclitaxel receive pretreatment to reduce the risk and severity of hypersensitivity reactions. The preferred regimen includes a combination of a corticosteroid (such as dexamethasone), an antihistamine (diphenhydramine or equivalent), and an Hj antagonist (such as cimetidine or ranitidine). Omeprazole and other PPIs will not block Hj-receptor sites and do not provide protection against hypersensitivity reactions. 

Prepare and administer using glass or non-PVC IV bags and tubing Premedicate patients to prevent hypersensitivity reactions dexamethasone 20 mg IV or orally 12 hours and 6 hours prior to paclitaxel, and diphenhydramine 50 mg IV 30 minutes prior to paclitaxel, and ranitidine 50 mg IV or cimetidine 300 mg IV 30 minutes prior to paclitaxel Reduce dose in patients with elevated total bilirubin (>1.5 mg/dL) and/or elevated transaminases (guidelines not well established)... 

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. 

Hypersensitivity reactions have occurred in patients receiving paclitaxel infusions of short duration (1-6 hours), but largely are averted by pretreatment with dexamethasone, diphenhydramine, and histamine receptor antagonists. Premedication is not necessary with 96-hour infusions. Many patients experience asymptomatic bradycardia, and occasional episodes of silent ventricular tachycardia also occur and resolve spontaneously during 3- or 24-hour infusions. 

In vitro studies with human liver tissue suggest that no metabolic interactions are likely to occur between paclitaxel and cimetidine, dexamethasone or diphenhydramine. Cremophor may inhibit the intracellular uptake and metabolism of paclitaxel. 

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. 

The water-soluble amphiphilic copolymers of MPC and -butyl methacrylate (BMA) have been extensively studied for DDS applications. The PBMA units assemble in water as a result of the hydrophobic effect and the copolymers form aggregates that can solubilize hydrophobic bioactive agents in the core PBMA segments. Paclitaxel, a very hydrophobic anticancer drug that is poorly soluble in aqueous medium (<0.3 pg mL ), can be better dissolved at more than 2 mg mL using P(MPC-Z)-BMA) block copolymers. Recently, Ishikawa et aZ. developed an emulsion lotion containing commercially available P(MPC-co-BMA) for the controlled release of water-insoluble diphenhydramine, which is a widely used antihistamine for... 

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. 

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