A Review of Trospium (SANCTURA) for Overactive Bladder

The Food and Drug Administration (FDA) approved the decade-old European drug trospium (SANCTURA) in May 2004 for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and urinary frequency. Trospium offers nothing special over drugs already on the market to treat overactive bladder.

Trospium belongs to the family of drugs known as anticholinergics. These drugs block the effects of acetylcholine, a nerve transmitter. Drugs with anticholinergic effects (including antidepressants, antihistamines, antipsychotics, drugs for intestinal problems, and antiparkinsonians) inhibit the secretion of acid in the stomach, slow the passage of food through the digestive system, inhibit the production of saliva, sweat, and bronchial secretions, and increase the heart rate and blood pressure. Adverse effects of these drugs include dry mouth, constipation, difficulty urinating, confusion, worsening of glaucoma, blurred vision, and short-term memory problems (see box).

The objective of treating overactive bladder is to relax the muscle of the bladder wall, called the detrusor muscle, so that it is capable of holding more urine for a longer period of time.

The anticholinergic drugs currently on the market approved to treat overactive bladder are tolterodine (DETROL, DETROL LA), oxybutynin (DITROPAN, DITROPAN XL), hyocyamine (LEVSIN), and propantheline (PRO-BANTHINE). The use of these drugs and trospium is limited by their well-recognized adverse effects including dry mouth, constipation, urinary retention, dry skin, vision disturbances, tachycardia (rapid heart rate), and changes in mental status.

The remainder of this article is based primarily on publicly available FDA review documents posted on Drugs@FDA, a catalog of FDA approved drugs, that can be found on the agency’s Web Site at: www.accessdata.fda.gov/scripts/
cder/drugsatfda/index.cfm. In many cases, we have found the FDA reviews of new drugs to be more informative than the peer reviewed medical literature. These reviews are independent of the manufacturer submitting the data. Sometimes studies are submitted and reviewed by the agency that are never published in medical literature because their results do not shine the brightest light on the drug being reviewed.

Indevus Pharmaceuticals Inc. submitted two 12-week-long clinical trials conducted in the U.S. in support of trospium’s approval. The first trial involved 509 patients, 253 randomly assigned to take trospium and 259 a placebo. The trial measured the change-from-baseline in average daily urinary frequency and average weekly number of urge incontinence episodes. These are called the primary endpoints of the trial. The table summarizes the results of this trial.

In this trial, the differences between the placebo and trospium were quite small for the primary endpoints of urinary frequency and urge incontinence, 1.1 and 1.5 episodes respectively. Though small, these differences were statistically significant.

The second U.S. clinical trial involved 325 patients randomly assigned to take a placebo and 323 patients given trospium. The design of the two U.S. trials were nearly identical down to measuring the same primary endpoints: urinary frequency and urge incontinence. The table below summarizes the results of the second trial.

Again the difference in this trial between the placebo and trospium were small for the primary endpoints of urinary frequency and urge incontinence episodes which were 0.9 and 4.0, respectively. As in the first trial, these differences were statistically significant.

One comment made by the FDA Medical Officer responsible for the review of trospium is worth noting. Indevus Pharmaceuticals believed that trospium would enter the central nervous system in very small amounts and thus reduce the potential for central nervous system- (CNS-) related adverse effects such as delirium and sedation. In response the FDA Medical Officer wrote:

Despite the theoretical potential for Sanctura to reduce CNS-related adverse reactions (and acknowledging the overall low rates of reported CNS adverse events in this NDA), the evidence is not yet sufficient to conclude that Sanctura is better than other anticholinergic medications or equivalent to placebo for CNS-related adverse reactions.

Our opinion of trospium is best summarized by the editors of The Medical Letter on Drugs and Therapeutics, a source we frequently cite because its independence from drug company influence, who reviewed the drug in their August 2, 2004 issue:

Trospium appears to offer no advantage over long-acting anticholinergics for treatment of overactive bladder, and its poor absorption from the gastrointestinal tract could be problematic. None of these drugs are as effective as advertisements to the public have suggested.

What You Can Do

You should wait at least seven years before taking trospium. This drug is nothing special.