ix21@sdcc6.UUCP (David Whiteman) (08/16/85)
Recently there has been several postings to net.med requesting
information about terfenadine. I hope this information is useful.
From The Medical Letter of Drugs and Therapeutics Vol 27 (issue 693)
August 2, 1985
Terfenadine - A Non-Sedating Antihistamine
Terfenadine (Seldane -- Merrell Dow), a new anithistamine, was recently
marketed in the USA for relief of symptoms associated with seasonal
allergic rhinitis. It is claimed to be no more sedating than placebo.
Mechanism of Action -- Terfenadine is a histamine H1-receptor antagonist
that binds mainily to peripheral H1 receptors, inhibiting the skin
reaction to intradermal injection of histamine. In animals, only small
amounts of terfenadine cross the blood-brain barrier (JK Woodward and NL
Munro, Arzneinmittelforsch, 32 (9a):1154, 1982; NL Wiech and JS Martin,
Arzneimittelforsch, 32 (9a):1167, 1982).
Pharmacokinetics -- Terfenadine is readily absorbed from the
gastrointestinal tract; plasma concentrations reach a peak one to two
hours after a single dose (RA Okerholm et al , Biopharm Drug Dispos,
2:185, 1981). Suppression of the histamine-induced skin-wheal response
begins in one to two hours, reaches a maximum in three to four hours, and
is maintained for about 12 hours. Terfenadine is metabolized in the
liver and excreted in urine and feces (DA Garteiz et al,
Arzneimittelforsch, 32(9a):1185, 1982).
Clinical Trials -- In a double-blind seven-day trial, moderate to
complete relief of symptoms of seasonal allergic rhinitis was achieved in
68 of 113 patients (60%) treated with terfenadine (60 mg bid), 71 of 119
patients (60%) taking 4 mg tid of chlorpheniramine maleate
(Chlor-Trimeton; and others), and 34 of 199 (30%) taking placebo (JP Kemp
et al, Ann Allergy, 54:502, June 1985). Another trial compared 60 mg bid
of terfenadine with 120 mg bid for seven days in 77 patients; both
dosages were associated with good or complete relief of symptoms in about
60% of patients (JC Murphy-O'Connor et al, J Int Med Res, 12:333,1984).
In a promotional brochure, the manufacturer describes some unpublished
multicenter studies that found the drug effective in about 70% of
patients; in one study, 53% of patients reported good to excellent
results with terfenadine.
A two-week trial found terfenadine (60 mg bid), chlorpheniramine (8
mg bid), and placebo similarly effective in relieving symptoms of
perennial rhinitis (J Brostoff and JDF Lockhart, Postgrad Med J, 58:422,
1982); terfenadine is not approved for marketing for this indication in
the USA. The drug has also been tried for histamine-related skin
disorders; the results of some studies sugges it may be effective for
treatment of chronic idiopathic urticaria (R Cerio and MH Lessof, Clin
Allergy, 14:139, 1984; EM Sorkin and RC Heel, Drugs, 29:34, 1985).
Adverse Effects -- The Manufacturer's claim that terfenadine is no more
sedating than placebo appears to be correct (M Weiner,
Arzneimittelforsch, 32 (9a):1193, 1982; TA Roehrs et al, Sleep,7:137,
1984; T Betts et al, Br Med J, 288:281, 1984). One Medical Letter
consultant reports that in his practice about a dozen patients taking
terfenadine have complained of insomnia. The results of pharmacological
studies indicate that terfenadine has no anticholinergic activity (VK
Kulshrestha et al, Br J Clin Pharmacol, 6:25, 1978), but in clinical
trials the incidence of anticholinergic effects was similar to that
reported with other antihistamines. Other adverse effects reported by
patients taking terfenadine have included headache, drowsiness, fatigue,
dry mouth, sore throat, nausea, nasal stuffiness, cough, weakiness,
dizziness, and abdominal distress, but the incidence of these effects in
clinical trials has generally been comparable to that in patients taking
placebo.
Dosage and Administration -- The dosage of terfenadine recommended for
patients more than 12 years old is one 60-mg tablet twice daily; safety
and effectiveness for children less than 12 years is not established.
The drug is not recommend for use during pregnancy or lacation because
the results of reproductive studies in animals sggest the possibility of
harmful effects on the fetus or nursing infant.
Cost -- Seldane costs the pharmacist $43.86 for 100 60-mg tablets
(Average Wholesale Price) compared to $6.52 for 100 4-mg tablets opf
Chlor-Trimeton, and an average of 80 cents for 100 4-mg tablets of generic
chlorpheniramine maleate, according to Drug Topics Red Book, 1985 and
July Update. Costs to the patient will be higher.
Conclusion -- Terfenadine appears to be non-sedating and as effective as
chlorpheniramine in relieving symptoms of seasonal allergic rhinitis, but
it is much more expensive, and many patients do not obtain even moderate
relief of symptoms. If further experience does not uncover any serious
adverse effects, terfenadine could be a useful alternative for patients who
cannot tolerate the sedative effects of other anitihistamines.
--
----
David Whiteman,
University of California, San Diego