Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Zelmac (Novartis)
6 mg tablets
Approved indication: irritable bowel syndrome in women
Australian Medicines Handbook Section 12.2.1
The cause of irritable bowel syndrome is uncertain. As there are several possible mechanisms a variety of drugs have been used in treatment. There has been interest in drugs acting on 5-HT receptors because of the effects of serotonin in the gastrointestinal tract.
Tegaserod is a partial agonist of the 5-HT4 receptor. It stimulates the peristaltic reflex and accelerates gastrointestinal transit. Tegaserod may therefore have a role in patients with irritable bowel syndrome who are predominantly troubled by constipation.
A double-blind trial randomised 881 patients with constipation-predominant irritable bowel syndrome to take tegaserod or a placebo for 12 weeks. Tegaserod produced statistically significant subjective improvements in bowel movements and abdominal discomfort. There was a non-significant improvement in bloating.1
Patients take tegaserod twice a day before meals. Its bioavailability is only10% and this is reduced by food. Most of the dose is excreted unchanged in the faeces, but a metabolite is produced which is excreted in the urine. Liver impairment increases the plasma concentrations of tegaserod.
Adverse reactions to tegaserod most frequently involve the gastrointestinal tract. The effect of the drug will result in approximately 9% of patients developing diarrhoea. Other adverse events occur with a frequency similar to that of placebo.
There is a large placebo response in patients with irritable bowel syndrome. In the largest study of tegaserod 43.5% of patients responded, but so did 38.8% of the patients given a placebo. The therapeutic advantage of tegaserod appears to decline with time so it should be discontinued if there has been no response after one month of treatment. In patients who respond, the maximum duration of treatment should be 12 weeks. As the number of men in the clinical trails was limited, tegaserod is only approved for women with constipation-predominant irritable bowel syndrome.
