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Substitution of Topamax with multiple generic formulations associated with greater health care costs, increased risk of hospitalization, injuries, findings suggest

Wednesday, June 24 2009 | Comments

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What's This? Patients with epilepsy who use multiple generic formulations of topiramate seem to incur higher health care costs and have higher rates of hospitalizations and injuries relative to patients who use the brand-name version of the drug (Ortho-McNeil-Janssen Pharmaceuticals Inc.'s Topamax), according to findings from a retrospective study.

The study researchers noted that there is concern among physicians regarding generic substitution of antiepileptic drugs (AEDs) and other "narrow therapeutic index" drugs because of the small differences between therapeutic and toxic doses with these agents, as well as the need for careful dosage adjustment and monitoring. This concern, they added, is compounded by the availability of multiple generic formulations of individual AEDs.

In the current analysis, which relied on medical and pharmacy claims data for patients in Quebec, the investigators evaluated branded and generic drug use patterns for 8 AEDs and 4 non-AEDs used to manage other chronic conditions (angina, depression, hypertension, and hyperlipidemia). They also evaluated the clinical and economic consequences of substituting >=1 generic formulations for the brand-name formulation of topiramate.

In general, generic substitution rates were lower for the AEDs (30.5% for drugs with generic formulations approved after 2000 and 18.2% for drugs with generic formulations approved before 2000) than for the non-AEDs (35.9%). In addition, switching back to a branded formulation from a generic was more common with the AEDs, especially the older AEDs. Switching between drugs of the same therapeutic class was also more common with the AEDs than with the non-AEDs.

Among the users of generic AEDs, the proportion of patients who used multiple generic formulations ranged from 23.0% with topiramate to 48.7% with valproate (mean of 1.4-2.8 versions per patient).

In the topiramate analysis, the researchers analyzed data for 948 patients. The observation period for these patients was split into periods of brand use (1,105 person-years), single-generic use (233 person-years), or multiple-generic use (92 person-years).

In an adjusted analysis, the periods of multiple-generic use were associated with greater use of other drugs, including other AEDs (incidence rate ratio [IRR], 1.16; 95% CI, 1.09-1.23) and non-AEDs (IRR, 1.31; 95% CI, 1.28-1.35), as compared with periods of brand use. Similarly, multiple-generic use was associated with a 65% higher hospitalization rate as compared with brand use (0.83 vs 0.48 visit per person-year; IRR, 1.65 [95% CI, 1.28-2.13]) and a 43% longer hospital stay (3.9 vs 2.6 days per person-year; IRR, 1.43 [95% CI, 1.27-1.60]).

These differences were less pronounced when single-generic use was compared with brand use (IRR for hospitalization, 1.08 [95% CI, 0.88-1.34]; IRR for length of stay, 1.12 [95% CI, 1.03-1.23]).

The data also revealed that the risk of head injury or fractures was nearly 3 times higher during periods of multiple-generic use as compared with periods of brand use (hazard ratio, 2.84; 95% CI, 1.24-6.48).

The cost of topiramate therapy was lower with single- and multiple-generic use as compared with brand use. However, single- and multiple-generic use were both associated with higher medical services costs (approximately $514 and $866, respectively, at the current exchange rate) and higher total health care costs (approximately $356 and $1,491, respectively). The difference in total health care costs between brand use and multiple-generic use was statistically significant (cost ratio, 1.21; P=.042).

These findings are consistent with previous research showing increased health care use and costs associated with switching from brand-name to generic formulations of AEDs, the authors commented.

"[T]hese results call into question the effectiveness of generic substitution policies pertaining to AEDs as a means to control costs, under the assumption that bioequivalence standards result in comparable clinical effectiveness." (Duh MS, et al. Neurology 2009;72:2122-2129.)

Ortho-McNeil Janssen provided funding for the study.

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