Upon its introduction in 1987, fluoxetine revolutionized drug therapy for mood disorders and has become a cornerstone in depression treatment. After 14 years of being the sole manufacturer of fluoxetine (under the brand name Prozac), Eli Lilly and Company’s exclusivity patent expired.1 Generic fluoxetine is now available through multiple manufacturers.
While use of generic fluoxetine rather than Prozac will decrease medication costs, the question arises: Is the brand-name drug more effective than its generic equivalent? Some anecdotal reports have suggested a clinical difference, but these claims have not yet been supported in the literature.
Some clinicians have found that select patients require a higher dosage of generic fluoxetine than Prozac to control their symptoms, but several issues may contribute to these increased requirements. First, depression and depressive symptoms wax and wane; an increase in symptoms may be part of the course of illness rather than differences between brand and generic formulations.
Increased symptoms may also reflect patient bias. The patient knows he or she is taking a generic and may be more inclined to notice or report symptoms. Additionally, some patients who believe generics are less effective than brand-name equivalents experience a reverse placebo effect—their belief that a generic drug is inferior diminishes its effectiveness. Finally, subtle differences in bioavailability and bioequivalence between the brand-name and generic drugs may be seen clinically.
To receive FDA approval, a generic drug must be proven to be therapeutically equivalent to its brand-name counterpart. This entails both pharmaceutical equivalence (identical amounts of the same ingredient in the same dosage form and route of administration) and bio-equivalence (comparable rate and extent to which the active ingredient is absorbed and becomes available at the site of action).2 Statistical analysis of pharmacokinetics includes evaluating measures such as area under the curve and peak concentration. The test drug and reference drug are compared by calculating the 90% confidence interval for their respective population geometric means. The calculated confidence interval should fall within the bioequivalence limit, typically between 80 and 125% for the population geometric mean. Other factors typically considered include the logarithmic transformation of pharmacokinetic data, methods to evaluate sequence effects, and evaluation of outlier data.3
Comparator generic drugs must be rigorously tested before receiving FDA approval. One would hope that the variability that may exist between the brand and generic product does not significantly change patient response.
To date, more than 20 companies have received approval or tentative approval for almost 50 generic fluoxetine products. The approval package data (which includes bioequivalency data) for these agents are not yet available.4
Still, there is no evidence that generic fluoxetine is less effective than Prozac, despite increased attention from patients, clinicians, and pharmaceutical companies. The bottom line is that each patient needs individual treatment. If symptoms increase or worsen, then increase the dosage, which would be done in any case. If adverse effects increase, lower the dosage. If a true difference is suspected in a specific patient, it should be promptly reported to the FDA, which evaluates drugs after marketing by regularly assessing product quality and investigating and evaluating allegations of drug product inequivalence.5
Cynthia A. Mascarenas, PharmD
Lisa M.Mican, PharmD
University of Texas Health Science Center at San Antonio
- McLean B. A bitter pill. Fortune, August 13, 2001.
- Vasquez CA, Vasquez R. Therapeutic equivalence guidelines: what the codes mean. Available at: www.pharmacytimes.com/GPR2.html.
- Center for Drug Evaluation and Research (CDER). Guidance for industry: statistical approaches to establishing bioequivalence. U.S. Department of Health and Human Services, Food and Drug Administration, 2001.
- CDER. New and generic drug approvals: 1998-2002. Available at: www.fda.gov/cder/approval/index.htm.
- U.S. Food and Drug Administration. Therapeutic equivalence of generic drugs (letter). Available at: www.pharmweb.net/forum/0086/1998/msg00010.html.