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Synopsis: Terfenadine1 is a selective H1- histamine receptor antagonist. The lack of significant terfenadine penetration into the CNS is probably responsible for its lack of CNS effects. Terfenadine neither impairs psychomotor performance nor adversely affects subjective feelings, nor enhances the depressant effects of concomitantly administered alcohol or benzodiazepines. In controlled studies, the incidence of sedation due to terfenadine was comparable with that of placebo and significantly less than that with conventional antihistamines. Clinical studies have shown terfenadine to be comparable in efficacy with other antihistamines while being superior to placebo in alleviating the symptoms of seasonal allergic rhinitis. Additionally, there is good evidence that it is similarly as effective when used in the treatment of perennial rhinitis and histamine- mediated skin diseases.
Thus, terfenadine offers a worthwhile improvement in side effect profile over ‘traditional’ antihistamines, and could well become an ‘agent of choice’ (along with other nonsedating antihistamines) in many patients in whom a histamine H1- receptor antagonist is indicated.
Pharmacodynamic Studies: Animal studies utilising in vitro receptor binding techniques have shown that terfenadine has specific H1-antihistamine activity. In vivo studies have shown terfenadine to preferentially bind to peripheral rather than central H1-histamine receptors. Since conventional antihistamines which produce sedation have greater affinities for central H1-histamine receptors, the lesser penetration of terfenadine into the CNS may be responsible for its apparent lack of CNS effects. Terfenadine was active in standard pharmacological tests in animals, including histamine-induced bronchoconstriction, lethality and skin wheals. Human studies have shown terfenadine 60mg suppresses almost 100% of the histamine-induced skin wheal response and that this suppression lasts for at least 12 hours after administration. Animal studies have indicated that terfenadine possesses minimal or no antiserotoninergic, anticholinergic or antiadrenergic activity.
As with other non-sedating antihistamines such as astemizole and mequitazine, psychomotor and visual function tests in man have shown that terfenadine does not impair psychomotor performance or adversely affect subjective feelings, in contrast to conventional antihistamines which were active in these tests. Terfenadine neither affects the EEG as sedative antihistamines are known to do, nor interacts with other depressant drugs (alcohol or benzodiazepines) to produce enhanced depressant effects.
Pharmacokinetic Studies: The kinetic properties of terfenadine have only been investigated in single-dose studies. Although radioimmunoassay has usually been used to quantitate terfenadine in plasma, when radiolabelled terfenadine was studied its absorption was greater than would be assumed based on radioimmunoassay data. The observed difference in timing between peak plasma concentrations of terfenadine and maximal effect is not due to slow or delayed absorption, as peak concentrations occur 1 to 2 hours after administration. The concentration of 14C-terfenadine equivalents in tissues appears to be dose related, with animal studies showing highest concentrations of the drug in the liver and lung, but only low concentrations in the CNS. Terfenadine undergoes rapid and extensive (99.5%) biotransformation. A carboxylic acid metabolite has been shown to possess antihistaminic activity and may play a role in the activity of terfenadine in vivo. The elimination half-life of terfenadine in healthy adults is 16 to 23 hours.
Therapeutic Trials: Terfenadine has been evaluated in clinical studies in patients with allergic rhinitis (mainly seasonal), and in histamine-related allergic dermatological disorders. Global assessment evaluations of the overall efficacy of terfenadine in alleviating the symptoms of allergic rhinitis have shown terfenadine to produce ‘good’ or ‘complete’ symptom resolution in a significantly greater percentage of patients than placebo. In comparative studies, terfenadine has been found to be equally as effective as other antihistamines. Only a few studies investigating the efficacy of terfenadine in perennial rhinitis have been published, with varying results, but an unpublished multicentre study demonstrated an equal efficacy of terfenadine and clemastine and that both drugs were significantly more effective than placebo. Similarly, terfenadine has been shown to be effective in the treatment of pruritus and skin conditions such as urticaria and eczema when associated with histamine release.
Side Effects: Although the most frequently reported adverse effect during terfenadine use has been sedation, it is important to note that this incidence (14%) is comparable with the percentage of patients reporting sedation while taking placebo in these studies. The range of the percentage of patients reporting sedation due to terfenadine, placebo or other traditional antihistamines in clinical studies was 2.2 to 20%, 4.4 to 20% and 18 to 60%, respectively. Dryness of the mouth has occurred in 2 to 5% of terfenadine-treated patients versus 4% and 3 to 8% of placebo and other antihistamine-treated patients, respectively.
Dosage and Administration: The recommended adult dosage of terfenadine is 60mg orally twice daily. In children aged 6 to 12 years the dosage is 30mg to 60mg twice daily depending upon bodyweight. In children aged 3 to 5 years, the dosage is 15mg twice daily.
Volume 29, Issue 1 , pp 34-56
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