Λεξικό .. Astemizole

A third generation H1-receptor antagonist which in recomanded doses creates sedation comparable to the incidence of sedation in patients receiving placebo and is not of clinical importance in most patients.  Astemizole seems to undergo extensive first-pass metabolism, and practically none of an oral dose is excreted in unchanged form in urine or feces.  Peak serum concentrations of astemizole after a conventional 10mg dose are extremely low, about 1 to 3ng/ml.  After a single 30mg dose, the mean serum half-life of astemizole plus desmethylastemizole is 9,5 days.  Steady-state serum concentrations of 5 to 6 ng/ml of astemizole plus hydroxylated metabolites are achieved after 4 to 6 weeks of daily dosing, and apparently further accumulation does not occur after this time. 

Astemizole binds to peripheral H1-receptor sites with far greater affinity than any other existing H1 receptor antagonist does, and exhibits a high degree of potency in multiple-dose studies, although not in single-dose studies.  10mg of Astemizole daily may significantly suppress the histamine-induced wheal and flare for weeks after the astemizole has been discontinued.  Even 8-14 weeks after discontinuation, some wheal and flare suppression and suppression of histamine inhalation tests may still be observed in some patients. 

Astemizole may cause appetite stimulation and inappropriate weight gain[2]..  A few patients receiving astemizole most of whom have admitted to taking an overdose, have had prolonged Q-T intervals and the ventricular arrhythmia known as torsade de pointes [1], accompanied by syncope and cardiac arrest.  Astemizole provides relief of allergic rhinoconjunctivitis symptoms. 

It relieves pruritus, new wheal formation and duration of whealing in patients with urticaria. There were 21 reports of fatality in association with terfenadine, 11 (52%) of which were either sudden deaths or those associated with a cardiac rate of rhythm reaction. Analysis of the WHO database for non-sedating drugs showed a similar pattern, with terfenadine being associated with the highest frequency of reports of potentially serious arrhythmias and of sudden death and death related to disturbances of cardiac rate and rhythm combined. Despite the limitations of spontaneous reporting systems, comparison of the benefit-risk profiles of drugs using this data within a class of drugs can provide valuable information, and pharmacovigilance of antihistamines (and all other agents) using this and other means should continue for the lifetime of their use in humans [3].

References

1. Craft, T.M.:  Torsade de pointes after astemizole overdose.  Br. Med. J. 1986;292:660.

2. Simons, et al:  Astemizole-induced torsade de pointes. Lancet 1988;2:624.

3. Routledge PA, Lindquist M, Edwards IR. Spontaneous reporting of suspected adverse reactions to antihistamines: a national and international perspective. Clin Exp Allergy. 1999 Jul;29 Suppl 3:240-6; discussion 247-50