Bradycardia paclitaxel

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. 

The authors of a review of the cardiac toxicity associated with paclitaxel in a number of studies concluded that the overall incidence of serious cardiac events is low (0.1%) (20). Heart block and conduction abnormalities occurred infrequently and were often asymptomatic. Sinus bradycardia was the most frequent, occurring in 30% of patients. The causal relation of paclitaxel to atrial and ventricular dysrhythmias and cardiac ischemia was not entirely clear. There did not appear to be any evidence of cumulative toxicity or augmentation of acute cardiac effects of the anthracydines. 

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). 

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. 

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. 

Taxanes Paclitaxel (853 Da) Docetaxel (861 Da) Sinus bradycardia, ventricular arrhythmias, myocardial ischemia, LV dysfunction, enhanced anthracycline cardiotoxicity... 

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