Dose-response relation between terfenadine (Seldane) and the QTc interval on the scalar electrocardiogram: distinguishing a drug effect from spontaneous variability.

The primary goal of this investigation was to describe the effect of terfenadine on the QT interval corrected for heart rate (QTc) of the scalar electrocardiogram (ECG). The design was double-blind, four-period crossover, dose escalation, which involved 28 normal healthy volunteers and 28 patients with stable cardiovascular disease. At baseline, the normal subjects had a mean QTc interval of 407 msec, whereas the patients with cardiovascular disease had a mean QTc interval of 417 msec (p<0.01). The largest increase in mean QTc on terfenadine was 24 msec in a normal subject and 28 msec in a patient with cardiovascular disease. The longest average QTc observed was 449 msec and 501 msec in any normal subject and patient with cardiovascular disease, respectively. Compared to baseline, terfenadine 60 mg twice daily is associated with a QTc increase of 6 msec in normal subjects and a 12 msec increase in patients with cardiovascular disease (p<0.01 vs baseline; p>0.05 when the two populations were compared). Although the QTc increase from baseline are statistically significant, the magnitude of the spontaneous variability in QTc in the same patients is much greater. Because 40 ECGs were obtained while taking placebo in each participant, the spontaneous variability in QTc interval with placebo was also described. Only one of the 28 normal subjects had a mean baseline QTc=440 msec, yet 14 of the 28 normal subjects had at lease one of the 40 placebo ECGs with a QTc=440 msec. The 28 patients with cardiovascular disease had a mean QTc at baseline of 417 msec; yet 20 of 28 had at lease one ECG on placebo with a QTc interval = 440 msec. On the average, the QTc fluctuated 56 msec in each patient during placebo administration. From the observed placebo variability, we calculated that an increase in QTc of=35 msec while receiving drug therapy is likely to represent a drug effect at the 95% confidence interval.

Double-blind placebo-controlled study of the efficacy of oral terfenadine in the treatment of chronic fatigue syndrome.

BACKGROUND: There is no established treatment for chronic fatigue syndrome (CFS), an illness characterized by disabling fatigue exacerbated by physical activity. A variety of immunologic abnormalities have been reported, including a high incidence of atopy and hypoergy or anergy. OBJECTIVE: Because of anecdotal reports and uncontrolled trials showing antihistamine efficacy in CFS, we evaluated the clinical efficacy of the antihistamine terfenadine (60 mg twice daily) in a placebo-controlled study. METHODS: Thirty patients with CFS were enrolled in a 2-month, double-blind, placebo-controlled trial of terfenadine. Participants underwent a battery of both immediate- and delayed-type hypersensitivity skin tests and completed a self-assessment questionnaire used to measure severity of symptoms, physical and social functioning, health perceptions, and mental health before each of six biweekly visits. RESULTS: Twenty-eight patients completed the trial. History of atopy and positive immediate skin test results were prevalent, 73% and 53%, respectively. No evidence for hypoergy or anergy after delayed-type hypersensitivity skin testing was found. No therapeutic benefit from terfenadine could be detected in terms of symptom amelioration, improved physical or social functioning, health perceptions, or mental health. A high incidence of atopy in patients with CFS was confirmed. CONCLUSION: Although this trial involved a small number of patients, the results suggest that terfenadine is unlikely to be of clinical benefit in treating CFS symptoms.

Safety and efficacy of terfenadine/pseudoephedrine versus clemastine/phenylpropanolamine in the treatment of seasonal allergic rhinitis.

A double-blind, randomized, placebo-controlled, parallel trial was conducted to compare the efficacy and safety of terfenadine, 60 mg (immediate-release)/pseudoephedrine hydrochloride, 120 mg (controlled-release) (T/Ps) and clemastine fumarate, 1.34 mg (immediate-release)/phenylpropanolamine, 75 mg (sustained-release) (C/Ph) in a combination tablet b.i.d. in 178 patients (12-59 years of age) with symptoms of seasonal allergic rhinitis. After seven days of treatment, the total symptom scores recorded in the diaries of 175 patients showed that both therapies had a highly significant overall treatment effect when compared with placebo (P < or = .02). The overall level of improvement, as well as improvement of individual symptoms, was similar with the two therapies. Total symptom scores assigned by physicians to 170 patients showed significant and similar levels of improvement with both therapies when compared with placebo (P < .01). The two therapies were also similar on physicians' evaluations of overall effectiveness. Both therapies relieved most histamine-mediated symptoms as well as nasal congestion, although only T/Ps showed improvement of the latter symptom in both the patients' diaries and physicians' evaluations. Among 178 patients, drowsiness and fatigue occurred more often in the C/Ph group (25% and 11.7% for the two adverse events, respectively) than in the T/Ps group (10.2% and 1.7%, respectively). The incidence of insomnia and dry mouth/nose/throat was higher with T/Ps (23.7% and 11.9%, respectively) than with C/Ph (6.7% and 3.3%, respectively). No serious or unexpected adverse events were reported. These results indicate that T/Ps and C/Ph are both superior to placebo and equally effective in the treatment of symptoms of seasonal allergic rhinitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of terfenadine in asthmatic patients.

The bronchodilator effect of terfenadine, 60-mg or 120-mg single dose, and 1 week twice daily dosing, was evaluated in 12 allergic asthmatic patients. When compared with baseline, FEV1 rose significantly for single dose 120 mg terfenadine at one, one and one-half, three, five and one-half, and six hours and for 60 mg terfenadine at three, five and one-half, six, and eight hours postdose. Variations in patient response were observed. At steady state, 120 mg terfenadine b.i.d. showed consistent improvement over placebo from three to 12 hours postdosing but no improvement in FEV1 was noted for terfenadine, 60 mg b.i.d. There no longer was a statistically significant difference in mean FEV1 or percent change from baseline. Thus, terfenadine proved to be a safe and a mild bronchodilator; however, tachyphylaxis might develop to the bronchodilator effect after 1 week of continuous b.i.d. dosing.

Absence of food effects on the pharmacokinetics of terfenadine.

Administration of terfenadine (Seldane) immediately after a high fat breakfast slightly affects the rate but not the extent of absorption relative to fasting administration. Mean peak levels of the active metabolite were increased by 13 per cent but delayed by 0.9 h while AUC was virtually the same as when terfenadine was administered while fasting. Changes in rate of absorption may be due to delayed gastric emptying and more rapid terfenadine solubilization. In any case, these rate differences are unlikely to be clinically important in the absence of differences in extent of absorption.

Pharmacokinetics of terfenadine in healthy elderly subjects.

The pharmacokinetics of the terfenadine active metabolite, metabolite I, was examined in ten healthy elderly adults and ten younger adults after single-dose oral administration of 120-mg terfenadine. All subjects successfully completed the study without reporting sedation or other adverse events. Absorption was rapid in both the young and elderly. The mean Cmax was the same for both groups, 501 ng/mL, and occurred at 2.3 hours in the young subjects and 2.5 hours in elderly subjects. However, the apparent clearance was reduced by about 25% in the elderly. After correcting clearance for bodyweight, this difference was not statistically significant.

The homeless experience: clinic building in a community health discovery-learning project.

The concept of discovery learning is exemplified in this account of four students and their instructor who began and developed a nurse-run clinic for the homeless in a community health project. The students were registered nurses returning for their bachelor's degrees. They experienced frustration at learning the difference between care based on their assessments of patients' needs and care geared to clients' assessments of desired interventions. The journals that they kept reveal self-discovery as well as new respect for other humans. In addition, a new type of community care emerged, which gives all indications of surviving.