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You should wait at least seven years from the date of release to take any new drug unless it is one of those rare “breakthrough” drugs that offers you a documented therapeutic advantage over older proven drugs. New drugs are tested in a relatively small number of people before being released, and serious adverse effects or life-threatening drug interactions may not be detected until the new drug has been taken by hundreds of thousands of... |
You should wait at least seven years from the date of release to take any new drug unless it is one of those rare “breakthrough” drugs that offers you a documented therapeutic advantage over older proven drugs. New drugs are tested in a relatively small number of people before being released, and serious adverse effects or life-threatening drug interactions may not be detected until the new drug has been taken by hundreds of thousands of people. A number of new drugs have been withdrawn within their first seven years after release. Also, warnings about serious new adverse reactions have been added to the labeling of a number of drugs, or new drug interactions have been detected, usually within the first seven years after a drug’s release. |
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WARNING: SPECIAL MENTAL AND PHYSICAL ADVERSE EFFECTS Older adults are especially sensitive to the harmful anticholinergic effects of these drugs. Drugs in this family should not be used unless absolutely necessary. Mental Effects: confusion, delirium, short-term memory problems, disorientation, and impaired attention Physical Effects: dry mouth, constipation, difficulty urinating (especially for a man with an enlarged prostate), blurred vision, decreased sweating with increased body temperature, sexual dysfunction, and worsening of glaucoma |
Solifenacin (VESICARE) and darifenacin (ENABLEX) were approved by the Food and Drug Administration (FDA) in late 2004. Their approvals expand to seven the number of very similar drugs marketed for the treatment of overactive bladder in the
We reviewed trospium in the November 2004 issue of Worst Pills, Best Pills News. Information can be found on the other drugs in the 2005 edition of Worst Pills, Best Pills or on this web site.
Solifenacin and darifenacin belong to the family of drugs known as anticholinergics. These drugs block the effects of acetylcholine, a nerve transmitter. Drugs with anticholinergic effects include antidepressants, antihistamines, antipsychotics, drugs for intestinal problems, and drugs for Parkinson’s disease. These drugs 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 the box on Anticholinergic Effects).
We used two primary sources of information to prepare this review. First, we evaluated the FDA-approved professional product labels, or package inserts, for solifenacin and darifenacin. We also analyzed the publicly available FDA reviews of the data submitted by the manufacturers of these drugs in support of their approval. The FDA reviews of new drugs are held to higher standards than the studies found in the published, peer-reviewed medical literature, and often these reviews give a much more realistic picture of the therapeutic value of new drugs than medical journal or media articles.
The FDA reviews for solifenacin can be found on the agency’s Web site at www.fda.gov/cder/foi/nda/2004/21-518_VesiCare.htm.
In support for solifenacin’s approval, Yamanouchi Pharma America, Inc., the drug’s manufacturer, submitted four clinical trials to the FDA. That formed the basis for solifenacin’s approval. The main result or primary endpoint, for these studies was the average change in the number of urinations per 24 hours from the beginning of a study until completion of a study at 12 weeks. To count towards solifenacin’s approval, the approval had to be statistically significantly different than a placebo.
A statistically significant difference does not necessarily mean that there is a noticeable benefit for patients. Overall in these four studies, the average reduction in the number of urinations per 24 hours after 12 weeks of treatment was 2.7 compared to 1.4 for those patients taking the placebo. This is a difference, on average, of only 1.3 urinations per 24 hours.
Solifenacin is not an inexpensive drug. At a popular Internet pharmacy the cost of a one-month supply, 30 tablets of the 5 milligram strength, is $100.00. At the same pharmacy the cost of 60 generic oxybutynin 5 milligram tablets, also a one-month supply, is $12.99. This is a savings of $87.01 per month or $1,044.12 per year.
The publicly available reviews of darifenacin are located on the FDA’s Web site at http://www.fda.gov/cder/foi/nda/2004/21-513_Enablex.htm.
Novartis Pharmaceuticals Corporation submitted three main clinical trials to the FDA in support of darifenacin’s approval. These three trials were all 12 weeks in duration just as they were for solifenacin. In the trials the primary endpoint, the basis for approving the drug, was the number of incontinent episodes per week. However, the FDA statistical reviewer did analyses to calculate the average change in the number of urinations per 24 hours. This is the same endpoint that was used in approving solifenacin.
One of the darifenacin trials was conducted in
Like solifenacin, the cost of darifenacin is exorbitant. At a Washington, D.C.-area chain pharmacy, the cost of 30 darifenacin 15 milligram tablets is $117.99. Compare this to the cost oxybutynin at an Internet pharmacy, which is $12.99. This is a difference of $105.00 per month or $1,260.00 per year.
The editors of The Medical Letter on Drugs and Therapeutics, a highly respected independent source of drug information for health professionals, reviewed solifenacin and darifenacin in their
There is no convincing evidence that either solifenacin or darifenacin offers any advantage in efficacy or tolerability over other long-acting anticholinergics for treatment of overactive bladder. Darifenacin may have more potential for adverse drug interactions, but one short study suggested that it might have less effect on cognitive function than other anticholinergics. All of these drugs are only modestly more effective than placebo for this indication.
What You Can Do
You should avoid using solifenacin or darifenacin until January 2012. Both drugs are only modestly effective compared to a placebo, both carry the risk of significant harm to older adults (see the box above), and both are overpriced.
