Switch to generic drugs may affect efficacy of LUTS treatment, says US study
Tuesday, 5 May 2009- Switching patients from branded to generic urologic drugs led to deterioration of efficacy and more side effects, according to two studies reported during the recently concluded American Urological Association’s annual meeting held in Chicago.
Control of lower urinary tract symptoms (LUTS) decreased by as much as 42.5% when patients were switched to a generic alpha-blocker or 5 alpha-reductase inhibitor (5ARI), said Dr. Steven A. Kaplan of Weill Cornell Medical College in New York.
In patients with overactive bladder, switching to a generic anticholinergic led to increases in a wide range of symptoms and to a 40% increase in the frequency of side effects, according to Kaplan.
"Patients and their physicians need to be aware of the implications of switching to generic medications," said Kaplan. "This is not a statement that generics should go away or a statement that generics are bad. I think the statement is that people have to understand what generics are and make their decisions accordingly."
Since passage of the Hatch-Waxman bill in the US in the mid-1980s, generic drugs' share of prescriptions has increased from 12% to about 70%. From 2004 to 2008, prescriptions for generic drugs increased by 12% a year, whereas prescriptions for branded drugs decreased by 6% a year, said Kaplan.
In 2008, generic drugs accounted for 2.4 billion prescriptions compared with 1.4 billion for branded drugs.
Manufacturers of generic drugs have to clear a lower hurdle in the approval process, Kaplain said. They need only to demonstrate the bioequivalence of their drugs compared with branded versions.
In the US, the definition of bioequivalence encompasses the range from 80% to 125% of the active compound. That definition means that generics within a specific drug class can vary substantially in the bioavailability of the active compound and that generic versions of individual drugs within the class may exhibit just as much variability.
"The bottom line is that bioequivalence does not mean therapeutic equivalence," said Kaplan.
To examine the therapeutic implications of switching patients from branded to generic drugs, investigators studied 257 men with LUTS treated for at least six months with a branded medication. The drug was an alpha-blocker in 169 cases and a 5ARI in 88 cases.
In each case the patient was switched from a branded drug to a generic substitute by the patient's primary care physician or as required by a patient's insurance company. Kaplan and colleagues followed the men for 12 months after the switch.
Patients on an alpha-blocker had a mean baseline symptom score (IPSS) of 8.9. After the switch to a generic, the mean score increased to 12.9 at six months (P=0.02) and to 13.2 at 12 months (P=0.001).
Conversion from Uroxatral (alfuzosin) to a generic drug resulted in the greatest decline in efficacy (42.5%). Among men on a 5ARI, the mean IPSS increased from 11.3 at baseline to 14.7 at six months after the switch (P=0.02) and to 16.2 at 12 months (P=0.001).
The largest decrease in efficacy occurred in men who were switched from Avodart to generic finasteride (27.6%). The mean PSA value increased from 1.1 to 1.7 ng/mL in the 12 months after switching from Avodart (dutasteride) to generic finasteride and from 1.2 to 1.5 ng/mL in men switched from Proscar to generic finasteride. A third of patients in the Avodart group had more than a 0.75 ng/mL rise in PSA after the switch, as did 14% of the Proscar group.
"The PSA changes after the switch to generic finasteride could have been sufficient to trigger unnecessary biopsies," saidKaplan.
The frequency of dizziness, nasal congestion, and ejaculatory dysfunction increased by 2% to almost 5% after the switch from a branded to generic alpha-blocker. Kaplan said 26 men were switched back to a branded alpha-blocker because of adverse effects.
In a second report at the AUA meeting, Kaplan recounted a similar experience in patients with overactive bladder who were switched from branded to generic drugs.
The study involved 87 women and 69 men who were switched from a branded anticholinergic drug to generic oxybutynin. After the switch, the women had a 29.4% increase in the rate of urge incontinence and smaller increases in frequency and nocturia. Men had increased rates of urge incontinence, nocturia, and frequency.
Postvoid residual increased by 15 mL in women and by 18.9 mL in men after the switch. Following conversion from branded to generic drugs, the frequency of dry mouth and constipation increased in women by 36.4% and 23.01%, respectively, and by 39.5% in men.
The largest changes in efficacy and safety occurred with switches from Detrol LA and Vesicare to generic oxybutynin (P<0.01).
Source: Kaplan SA, et al., "Generic substitutes are neither as safe nor effective as branded medications: experience in men treated for lower urinary tract symptoms" AUA 2009; Abstract 1799; American Urological Association
