Long-term safety of tegaserod in patients with constipation-predominant irritable bowel syndrome.

BACKGROUND: Tegaserod is a 5-hydroxytryptamine-4 receptor partial agonist. Oral administration causes gastrointestinal effects resulting in increased gastrointestinal motility and attenuation of visceral sensation. AIM: : To determine the long-term safety and tolerability of tegaserod in patients suffering from irritable bowel syndrome with constipation as the predominant symptom of altered bowel habits. METHOD: A multicentre, open-label study with flexible dose titration of tegaserod in out-patients suffering from constipation-predominant irritable bowel syndrome. RESULTS: A total of 579 patients with constipation-predominant irritable bowel syndrome were treated with tegaserod. Of these, 304 (53%) completed the trial. The most common adverse events, classified as related to tegaserod for any dose, were mild and transient diarrhoea (10.1%), headache (8.3%), abdominal pain (7.4%) and flatulence (5.5%). Forty serious adverse events were reported in 25 patients (4.4% of patients) leading to discontinuation in six patients. There was one serious adverse event, acute abdominal pain, classified as possibly related to tegaserod. There were no consistent differences in adverse events between patients previously exposed to tegaserod and those treated de novo. No pattern-forming tegaserod-related abnormalities in haematological and biochemical laboratory tests, urinalysis, blood pressure, pulse rate or electrocardiograms were found. CONCLUSIONS: Tegaserod appears to be well tolerated in the treatment of patients with constipation-predominant irritable bowel syndrome. The adverse event profile, clinical laboratory evaluations, vital signs and electrocardiogram recordings revealed no evidence of any unexpected adverse events, and suggest that treatment is safe over a 12-month period.

Fluticasone propionate 1 mg daily and beclomethasone dipropionate 2 mg daily: a comparison over 1 yr.

This study was designed primarily to assess the safety and tolerability of fluticasone propionate (FP) 1 mg day-1 by comparison with beclomethasone dipropionate (BDP) 2 mg day-1 over a 12-month study period. Lung function data were also recorded and used to determine whether the potency ratio between the two inhaled corticosteroids observed in previous studies was maintained in the long-term. Two hundred and thirteen patients with an established clinical history of severe chronic asthma and who were currently receiving between 1000 micrograms and 2000 micrograms day-1 of inhaled steroids were randomized to treatment in a ratio of 3:1 for FP:BDP (159 patients FP; 54 patients BDP), both via metered dose inhalers. Both treatments were well tolerated with a similar adverse event profile. No unexpected adverse events were recorded. Most adverse events were related to the patients' asthma, an intercurrent infection or underlying atopy. The incidence of pharmacologically predictable adverse events was equally low in both treatment groups as was the incidence of events suggestive of systemic steroid effect. Mean serum cortisol levels remained within the normal range at all visits for both treatments. At 12 months, however, the mean cortisol levels for the FP group had risen 4% above the baseline value but had dropped 15% below for the BDP group, giving a ratio of FP:BDP of 1.22; P = 0.01; 95% confidence limits (CL) 1.05-1.43. Fluticasone propionate 1 mg day-1 was at least as effective as BDP 2 mg day-1 in improving lung function (PEF, FEV1 and FVC) over this period. Moreover, the difference in FEV1 values at 6 months was significantly greater for the FP group than for the BDP group (P = 0.04; difference = 0.12 1; 95% CL = 0.01, 0.24 1). The difference between treatments in the amount of FEV1 reversibility was also significantly greater for FP at 12 months (difference in treatments = -3%; 95% CL = - 7-0%; P = 0.044). This study supports previous studies and suggests that FP is likely to be of benefit in the long-term treatment of chronic severe asthma.

Long-term effects of a tube extension on bronchodilator treatment with pressurized aerosol.

The long-term effects of a tube extension to the terbutaline sulphate aerosol were studied in 23 patients. The trial was of open, randomised, cross-over design, and compared the ordinary actuator with the tube extension over two 3-week periods. Lung function before and after bronchodilator was measured at the start of the trial, at the treatment cross-over and at the end of the trial. The mean baseline FEV1 value obtained following 3 weeks of treatment with the tube extension was significantly greater (P less than 0.05) than that following treatment with the ordinary actuator. Treatment with the latter, however, produced significantly greater FEV1 values than at the start of the trial (P less than 0.05). At home, the patients recorded symptoms daily, as well as PEF each morning and evening. With the tube extension, the increase in PEF was significantly larger (P less than 0.05) than with the ordinary actuator. There were no differences with regard to symptom score.

Double-blind comparative trial of Nuelin Depot and TheoDur with adjusted dosage in asthmatic adults.

Equivalent doses of two sustained release preparations of theophylline, Nuelin Depot and TheoDur, were compared in a double blind, cross-over study. Twenty adult outpatients with COLD were given adjusted doses of the two preparations to reach a peak value of theophylline in steady state within the therapeutic range. The study consisted of two 14-day periods and airway function parametres, plasma concentrations, asthma symptoms, and side effects were recorded the last day in each period. In addition morning PEFR, use of beta 2 stimulant aerosol and number of nightly attacks were recorded daily. As judged from the peak-trough variation of 24.8 mumol for Nuelin Depot and 26.3 mumol/l for TheoDur as well as the tmax of 4.3 hours for Nuelin and 3.6 hours for TheoDur, both products produced a similar plasma profile. No statistically significant differences were found between the two preparations with respect to airway function parameters, relief of asthma symptoms, need for beta 2-stimulant aerosol or side effects. In conclusion these two sustained release preparations should be considered equivalent for practical use.

Beclomethasone dipropionate aerosol in reversible obstructive airways disease. A clinical evaluation of one year's treatment.

Seven patients with reversible obstructive airways disease, who were unsatisfactorily relieved by conventional bronchodilating drugs, were admitted to a 1-year-long therapeutic trial with beclomethasone dipropionate aerosol, 400 mug a day. After 3 weeks of treatment the mean values of VC, FEV, and PEFR were increased by about 100 per cent of the pretreatmetn values, and the consumption of self-administered bronchodilators was markedly diminished. Throughout the trial the occupationa diability and need for hospitalization were negligible compared with the previous year. Development of tolerance to the drug was not observed during the trial. The adrenocortical function remained unaffected, as judged by the plasma cortisol levels and adrenocortical stimulation tests. Continuously low normal levels of excreted urinary 17-ketogenic-steroids might indicate a very slight adrenal suppression.