Hypotension paclitaxel

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... 

Myelosuppression is the major side effect of paclitaxel. Alopecia is common, as is reversible dose-related peripheral neuropathy. Most patients have mild numbness and tingling of the fingers and toes beginning a few days after treatment. Mild muscle and joint aching also may begin 2 or 3 days after initiation of therapy. Nausea is usually mild or absent. Severe hypersensitivity reactions may occur. Cardiovascular side effects, consisting of mild hypotension and bradycardia, have been noted in up to 25% of patients. 

Paclitaxel Inhibits mitosis Breast cancer, non-small cell and small cell lung cancer, ovarian cancer, gastroesophageal cancer, prostate cancer, bladder cancer, head and neck cancer Nausea, vomiting, hypotension, arrhythmias, hypersensitivity Myelosuppression, peripheral sensory neuropathy... 

Paclitaxel causes disturbances in cardiac rhythm, but the relevance of these effects has not been fully elucidated. Originally, aU patients in trials of paclitaxel were under continuous cardiac monitoring, owing to the risk of hypersensitivity reactions, and cardiac disturbances were therefore more likely to be detected. Many trials limited eligibility to patients without a history of cardiac abnormalities and to those who were not taking medications likely to alter cardiac conduction. The incidence of cardiac dysrhythmias in the population under study not treated with paclitaxel is unknown, and it is therefore not always possible to attribute dysrhythmias to paclitaxel in these patients. The Cremophor EL vehicle does not appear to be implicated in the incidence of dysrhythmias, although hypotension associated with hypersensitivity reactions may occur (13). 

Acute hypersensitivity reactions were common during phase 1 trials of paclitaxel, and this caused delays in the completion of many trials. Reactions were mild to severe and consisted of cutaneous flushing, bronchospasm, bradycardia, and hypotension the reactions occurred after either the first or second dose (48). The mechanism of these reactions is uncertain, but they are thought to be non-immunologically mediated, and direct histamine release by mast cells is probably responsible. A large dose of Cremophor EL is used in the formulation of paclitaxel, and this may play an important part in these hypersensitivity reactions Cremophor EL induces similar reactions in dogs by direct release of histamine (4). 

In a study of 32 patients, 84% of those who received paclitaxel developed hypersensitivity reactions characterized by hypotension, respiratory distress, and urticaria (35). These symptoms further confirm that histamine is likely to be the cause of the reaction. The majority of reactions (53%) occurred within 2-3.minutes after the administration of paclitaxel and 78% within 10 minutes. There was one fatal reaction, characterized by hypotension and asystole. Most reactions to paclitaxel occurred after the first or second dose, and hypersensitivity reactions were more common with shorter infusion schedules. Since the duration of the infusion affected the incidence of hypersensitivity reactions, an extension of the infusion duration was investigated. Longer infusion schedules were associated with a reduced incidence of hypersensitivity reactions, the frequency of severe reactions being reduced from 12% or more to 5% with longer infusion times (5,15,49). 

About 2% of all patients who receive paclitaxel with preventive premedication will develop a severe hypersensitivity reaction, characterized by dyspnea, hypotension, angioedema, and urticaria, and requiring treatment. Minor reactions occur in 39% of patients but do not require therapeutic intervention (7). 

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)... 

Paclitaxel An++, C+, M+, N+ Severe hypersensitivity reactions, including death, reported. Hypotension, bradycardia, ECG abnormalities, conduction abnomaalities may occur. Fatal myocardial Infarction 15 h into infusion reported. 

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