Bioavailability of carbamazepine from four different products and the occurrence of side effects

Olling, M.; Mensinga, Tjeerd T.; Barends, D. M.; Groen, C.; Lake, O. A.; Meulenbelt, Jan

doi:10.1002/(sici)1099-081x(199901)20:1<19::aid-bdd152>3.3.co;2-h

Cited by 12 publications

(22 citation statements)

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“…A large number of studies evaluating the clinical outcomes of generic substitution have concluded that the latter caused unexpected and negative effects [24][25][26][27]. For example, the increase in the generic market share in Sweden between 1972 and 1996 was found to be associated with the increase in the number of reported side effects for 7 of the 15 medicines studied [28].…”

Section: Discussionmentioning

confidence: 68%

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Generic and therapeutic substitutions: are they always ethical in their own terms?

2010

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Cost containment-driven drug substitution, whether generic or therapeutic, is defined as switching to another drug because it is cheaper. So far, such substitutions have drawn their public legitimacy from the general belief that they would not compromise the clinical interests of patients and certainly not violate their right to decline them if they did. This article does not enter the debate on whether or not such substitutions must give exclusive priority to the patient's interests and choices in order to be ethical. Indeed, it acknowledges the plurality of views on this matter. It simply argues that when such substitutions involve a cheaper drug that is known to have different effects and side effects, or even a drug whose effects and side effects are unknown, they are potentially deleterious to the patient, and that no competent and well-informed patient would ever consent to them. Such substitutions are thus unethical in their very own terms.

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Section: Discussionmentioning

confidence: 68%

“…Other studies have shown differences in the pharmacokinetic profile between brand and generic drugs with disparities that might affect clinical outcomes [27,[29][30][31]. Differences in formulation have also been noted in generic versions of some drugs [32,33].…”

Section: Discussionmentioning

confidence: 99%

Generic and therapeutic substitutions: are they always ethical in their own terms?

2010

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“…The safety and efficacy of generics have been questioned, particularly when there is generic substitution of antiepileptic, immunosuppressant, and psychotropic drugs . Increased seizures and side effects have been reported after antiepileptic drug (AED) generic substitution, attributed to differences in bioavailability allowed between brand and generic products . Rare cases of acute rejection in kidney transplant patients have been reported after conversion from reference to generic tacrolimus .…”

mentioning

confidence: 99%

Generic lamotrigine versus brand‐name Lamictal bioequivalence in patients with epilepsy: A field test of the FDA bioequivalence standard

et al. 2015

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SUMMARYObjective: To test the current U.S. Food and Drug Administration (FDA) bioequivalence standard in a comparison of generic and brand-name drug pharmacokinetic (PK) performance in "generic-brittle" patients with epilepsy under clinical use conditions. Methods: This randomized, double-blind, multiple-dose, steady-state, fully replicated bioequivalence study compared generic lamotrigine to brand-name Lamictal in "generic-brittle" patients with epilepsy (n = 34) who were already taking lamotrigine. Patients were repeatedly switched between masked Lamictal and generic lamotrigine. Intensive PK blood sampling at the end of each 2-week treatment period yielded two 12-h PK profiles for brand-name and generic forms for each patient. Steady-state area under the curve (AUC), peak plasma concentration (C max ), and minimum plasma concentration (C min ) data were subjected to conventional average bioequivalence (ABE) analysis, reference-scaled ABE analysis, and within-subject variability (WSV) comparisons. In addition, generic-versus-brand comparisons in individual patients were performed. Secondary clinical outcomes included seizure frequency and adverse events. Results: Generic demonstrated bioequivalence to brand. The 90% confidence intervals of the mean for steady-state AUC, C max , and C min for generic-versus-brand were 97.2-101.6%, 98.8-104.5%, and 93.4-101.0%, respectively. The WSV of generic and brand were also similar. Individual patient PK ratios for generic-versus-brand were similar but not identical, in part because brand-versus-brand profiles were not identical, even though subjects were rechallenged with the same product. Few subjects had seizure exacerbations or tolerability issues with product switching. One subject, however, reported 267 focal motor seizures, primarily on generic, although his brand and generic PK profiles were practically identical. Significance: Some neurologists question whether bioequivalence in healthy volunteers ensures therapeutic equivalence of brand and generic antiepileptic drugs in patients with epilepsy, who may be at increased risk for problems with brand-to-generic switching. Bioequivalence results in "generic-brittle" patients with epilepsy under clinical conditions support the soundness of the FDA bioequivalence standards. Adverse events on generic were not related to the small, allowable PK differences between generic and brand.

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“…Unfortunately, some other generic medicines in this dissolution test failed to achieve the 85% dissolution at 60 min. These differences in dissolution rate between the branded and their generic counterparts could impact the drugs' effectiveness and side-effects profiles [27].…”

Section: Discussionmentioning

confidence: 99%

The differences between the branded and generic medicines using solid dosage forms: In-vitro dissolution testing

Ameri

Nayuni

Kumar³

et al. 2012

Results in Pharma Sciences

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Bioavailability of carbamazepine from four different products and the occurrence of side effects

Cited by 12 publications

References 0 publications

Generic and therapeutic substitutions: are they always ethical in their own terms?

Generic and therapeutic substitutions: are they always ethical in their own terms?

Generic lamotrigine versus brand‐name Lamictal bioequivalence in patients with epilepsy: A field test of the FDA bioequivalence standard

The differences between the branded and generic medicines using solid dosage forms: In-vitro dissolution testing

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