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.
1 mg and 2 mg tablets
Approved indication: overactive bladder
Australian Medicines Handbook section 13.1.1
Incontinence is a common problem, but many cases can be helped by behavioural modification programs.1 Some cases are caused by detrusor instability. The symptoms of urinary frequency and urgency may improve with drug treatment. Tolterodine adds to the choice of anticholinergic drugs for this problem.
Tolterodine is a competitive antagonist at muscarinic receptors. This action reduces bladder contraction. Improvements in urodynamic function can be detected after two weeks of treatment.
Patients take tolterodine twice a day. It is well absorbed but is then extensively metabolised by the liver. The active metabolite also has an antimuscarinic action. This metabolism involves cytochrome P450 2D6, an enzyme of which some people have little. Clearance is reduced in these 'poor metabolisers', but, because of the way tolterodine and its active metabolite are bound to protein, the overall effect of the drug is unchanged. The dose should be reduced in patients with liver disease. Less than 1% of the drug is excreted unchanged in the urine, but a lower dose is recommended in patients with impaired renal function.
Although tolterodine increases the volume excreted per micturition, it has not significantly reduced the frequency in all of the placebo-controlled studies. One 12-week study of 293 patients compared tolterodine, oxybutynin and placebo. At the end of the study, frequency had respectively decreased by 21%, 20% and 11%. The corresponding increases in the volume excreted per micturition were 27%, 31% and 7%. In patients with urge incontinence, tolterodine reduced the number of incontinent episodes by 47% compared to 19% in the placebo group, however there was a 71% reduction in the oxybutynin group.2 The need for treatment should be reviewed after six months, but some studies suggest that the effect of tolterodine continues for up to a year of treatment.
The majority of patients will experience adverse effects during treatment with tolterodine. Some of these adverse effects are predictable because of the drug's action, for example dry mouth, constipation and blurred vision. Patients with narrow angle glaucoma should not take tolterodine. Other adverse effects of tolterodine include headache, dyspepsia and dry eyes. In the comparative study, oxybutynin caused more adverse effects and patient withdrawals than tolterodine.2 This should be interpreted with caution as the starting dose of oxybutynin in the study was higher than usual.
Tolterodine may interact with other drugs that have anticholinergic effects. There is also a potential for adverse interactions with drugs which have cholinergic effects, such as the cholinesterase inhibitors used in the treatment of dementia.
When considering drug treatment for patients with incontinence, prescribers will need to ask if the patient would prefer a drug which may be less efficacious, but might have fewer adverse effects. While tolterodine does appear to help some people with incontinence, its use for overactive bladder is more controversial.
A report from New Zealand suggests that tolterodine has been promoted for use by patients without incontinence as a strategy to expand the market for the drug.3 While there has been a campaign to raise awareness of overactive bladder in New Zealand, a systematic review concluded that anticholinergic drugs are of questionable clinical significance for the condition. Over 48 hours, patients will have one less micturition than patients taking a placebo, but they will be more than twice as likely to complain of a dry mouth.4
Notes on references
At the time the comment was prepared, information about this drug was available on the web site of the Food and Drug Administration in the USA (www.fda.gov).
At the time the comment was prepared, a scientific discussion about this drug was available on the web site of the European Agency for the Evaluation of Medicinal Products (www.emea.eu.int).
- Millard RJ. Uropharmacology in the management of incontinence. Aust Prescr 1992;15:66-9.
- Abrams P, Freeman R, Anderstrom C, Mattiasson A. Tolterodine, a new antimuscarinic agent: as effective but better tolerated than oxybutynin in patients with an overactive bladder. Br J Urol 1998;81:801-10.
- Toop L, Richards D, Dowell T, Tilyard M, Fraser T, Arroll B. Direct to consumer advertising of prescription drugs in New Zealand: for health or for profit? Christchurch: University of Otago; 2003.
- Herbison P, Hay-Smith J, Ellis G, Moore K. Effectiveness of anticholinergic drugs compared with placebo in the treatment of overactive bladder: systematic review. Br Med J 2003;326:841.