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.

Xenical (Roche)
120 mg capsules
Approved indication: obesity
Australian Medicines Handbook Section 12.10

Patients with a body mass index (see box) of 30 or more can be difficult to treat. (See'Obesity and its management' Aust Prescr 1999;22:12-6). These patients may benefit from orlistat in combination with a low calorie diet.

Orlistat inhibits lipase in the gut. This reduces the absorption of fat by approximately 30%. The decreased absorption of calories eventually leads to weight loss.

Two placebo-controlled trials have assessed the effect of orlistat on several hundred patients.1,2 The patients were given a diet which contained fewer calories than their daily energy needs. They took orlistat or placebo for a year then were re-randomised and switched to a diet designed to maintain their weight. The patients were followed up for a further year. During the first year of the trials the patients in one study lost an average of 10.3 kg with orlistat and 6.1 kg with placebo.1 In the second study the mean weight losses were 8.7 kg and 5.8 kg.2 During the second year of the trials patients who had been re-randomised to placebo put weight back on. Those who had continued on orlistat regained less weight. Some of the patients switched from placebo to orlistat lost a small amount of weight (0.9 kg).1

The recommended dose is 120 mg with each main meal. Very little of the dose is absorbed. The effect of orlistat on faecal fat can be seen within two days. Some metabolism may take place within the wall of the gut, but most of the drug is excreted unchanged in the faeces.

As orlistat reduces fat absorption most patients develop adverse effects including fatty stools, loose stools, faecal urgency, flatulence and incontinence. Most of the approximately 9% of patients who discontinued treatment because of adverse effects did so because of gastrointestinal problems.

Although orlistat reduces cholesterol concentrations, it also reduces the absorption of fat-soluble vitamins. Reduced vitamin K absorption could alter the control of patients taking warfarin. In the clinical trials no deficiencies developed so vitamin supplements may not be needed.

Orlistat increases the plasma concentration of pravastatin, but does not alter the pharmacokinetics of digoxin, glibenclamide or phenytoin. Acarbose, which acts on intestinal glucosidase enzymes, should not be prescribed with orlistat as the potential for interactions has not been studied.

Pooled data have revealed more cases of breast cancer in women taking orlistat than in those taking a placebo. The clinical relevance of this observation is uncertain, as is the effect of exposing the colonic mucosa to large amounts of fat.

The clinical trials show that orlistat will enable patients to lose approximately 4 kg more than they would by dieting. This difference is reduced when the patient is given a eucaloric (weight-maintaining) diet. Continuing a hypocaloric diet for two years is the subject of more research. The drug is likely to be even less effective if the patient does not change their lifestyle. One approach is to stop orlistat if the patient has not lost 5% of their weight after 12 weeks of treatment.