Bioequivalence, Drugs with Narrow Therapeutic Index and the Phenomenon of Biocreep: A Critical Analysis of the System for Generic Substitution

Gozzo, Lucia; Caraci, Filippo; Drago, Filippo

doi:10.3390/healthcare10081392

Cited by 12 publications

(15 citation statements)

References 76 publications

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“…Other explanations for variable concentrations could include owner noncompliance (including diet changes) or a change in drug manufacturing during the trial. When switching from 1 generic medication to another as much as a 40% difference in bioavailability can be observed for drugs not considered to be narrow therapeutic index drugs 43 . Given the lack of significant differences in ASD concentrations between CBD and placebo, these variations in ASD concentrations may reflect a normal change seen with ASD administration in dogs.…”

Section: Discussionmentioning

confidence: 99%

The efficacy and safety of cannabidiol as adjunct treatment for drug‐resistant idiopathic epilepsy in 51 dogs: A double‐blinded crossover study

Rozental,

Weisbeck,

Corsato Alvarenga

et al. 2023

Veterinary Internal Medicne

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BackgroundApproximately 30% of dogs with idiopathic epilepsy (IE) are drug‐resistant. Recent studies have suggested cannabidiol (CBD) may be an effective anticonvulsant in dogs with IE.ObjectiveTo evaluate the addition of CBD to antiseizure drugs (ASDs) on seizure frequency and to report adverse events in dogs with drug‐resistant IE.AnimalsFifty‐one dogs. Dogs having at least 2 seizures per month while receiving at least 1 ASD were included in the trial.MethodsDouble‐blinded placebo‐controlled crossover study. The 5 mg/kg/day dosage met futility requirements after 12 dogs, and a dosage of 9 mg/kg/day was used in the next 39 dogs. Dogs were randomly assigned to receive CBD or placebo for 3 months, with a 1‐month washout period between oils. Total numbers of seizures and seizure days were recorded. Diagnostic testing was performed periodically throughout the trial.ResultsAt the 9 mg/kg/day dose, the decrease in total seizure frequency was significant compared with placebo. A 24.1% decrease in seizure days occurred in dogs receiving CBD and a 5.8% increase occurred in dogs receiving placebo (P ≤ .05). No significant difference was found in the number of responders (≥50% decrease in total seizures or seizure days). Liver enzyme activities increased at both dosages. Decreased appetite and vomiting were more common in the CBD phase (P ≤ .05).Conclusions and Clinical ImportanceCannabidiol decreased total seizures and seizure days compared to placebo when administered to dogs PO at 9 mg/kg/day. Liver enzymes should be monitored with administration of CBD in dogs.

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Section: Discussionmentioning

confidence: 99%

The efficacy and safety of cannabidiol as adjunct treatment for drug‐resistant idiopathic epilepsy in 51 dogs: A double‐blinded crossover study

Rozental,

Weisbeck,

Corsato Alvarenga

et al. 2023

Veterinary Internal Medicne

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“…A uniform questionnaire was developed after an extensive literature review. [23][24][25] Initially piloted on 10 pharmacists, unclear questions or duplicates were modified or deleted. The instrumentation's adequacy was assessed as recommended for pilot studies.…”

Section: Data Collectionmentioning

confidence: 99%

Lebanese pharmacists’ knowledge of generic drugs and factors affecting their use and selection following the pandemic and the economic crisis: A pilot cross-sectional study

Mansour,

Hatem,

Ballout

et al. 2023

Journal of Generic Medicines

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Background Pharmacists are crucial in lowering pharmaceutical expenditures by substituting brand-name drugs for generic drugs. They are expected to understand the principles and practices of generic drug substitution for high-quality patient care. Some key areas of knowledge include bioequivalence and therapeutic equivalence, regulatory requirements, drug interchangeability, and adequate patient counseling. Objectives This study aims to assess the knowledge, perception, and practice of generic drug substitution among pharmacists in Lebanon following the crises and the factors affecting the prescription and selection of generic drugs. Methods A pilot descriptive cross-sectional study targeting 80 Lebanese pharmacists was conducted over 2 months (September-October 2022), in which data were collected using a uniform survey. Results Overall, pharmacists had a good knowledge of generic drugs in terms of active ingredients (97.5%), pharmaceutical form (85.0%), lower cost (88.7%), bioequivalence to the brand before (95.0%), and therapeutic equivalence. Nevertheless, 22.5% reported that generic drugs are less safe than brands, and 22.5% said they cause side effects or did not know. Among the possible factors that influence the prescription of generic drugs, 35.0% of pharmacists reported that the financial situation of the patient is among the least important factors, while the lack of possible alternatives (45.0%) and the difference in prices (40.0%) were the most important ones. The price of different generics on the market was among the most important factors (36.3%) affecting the selection of generic drugs, followed by the patient’s. preference (26.3%). Only 11.2% considered the information given by pharmaceutical firms could affect their choice, and 10.0% considered the presence or not of excipients with known effects in the formulation. Conclusion Most pharmacists in Lebanon were familiar with generic drugs and supported generic drug substitution. Factors affecting generic drug use and prescription should be further explored to clarify misconceptions and reduce possible adverse events.

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“…16 Nevertheless, this involves substituting the same chemical or biological entity at the exact dosage and pharmaceutical form with another product, presenting the same quality, efficacy, and safety profiles. 1,6 Once the marketing authorization file of a generic drug has been accepted, the national regulatory authority can register it, which allows doctors to prescribe it and pharmacists to consider it for substitution. 17,18 The bioequivalence studies guarantee the efficacy of a generic drug identical to that of the originator, but its tolerance may be different due to the disparity of excipients with known effects.…”

Section: Overview Of Generic Drug Substitutionmentioning

confidence: 99%

“…For example, some drugs have a narrow therapeutic index, which means that small dose or concentration changes can significantly impact the drug's effectiveness or safety. 6 In these cases, a healthcare provider may prefer to use the brand-name medication to ensure precise dosing. 7 Most recently, the coronavirus disease pandemic and the corresponding economic impact induced a lack of access to essential drugs, which encouraged the costeffective prescription of substitutes.…”

Section: Introductionmentioning

confidence: 99%

A comprehensive review addressing the factors influencing generic drug substitution

Jouni,

Mansour,

Hatem

et al. 2023

Journal of Generic Medicines

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Generic drug substitution is a common practice in healthcare systems worldwide to promote cost-saving treatments while maintaining therapeutic effectiveness. Several factors influence this substitution, including regulatory policies, safety and efficacy considerations, patient and physician preferences, and market dynamics. This review comprehensively analyzes how these factors interact and influence generic drug substitution in healthcare settings and across various therapeutic classes and highlight the importance of balancing cost-saving measures with maintaining patient safety and therapeutic efficacy. Policies and guidelines established by health authorities in each country influence the approval, interchangeability, and substitution of generic drugs. Bioequivalence and therapeutic equivalence are critical factors, particularly in drugs with narrow therapeutic indexes. Moreover, physicians’ acceptance and willingness to prescribe generic drugs, as well as patient acceptance and compliance with generic drug use, play a vital role in promoting generic substitution.

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Bioequivalence, Drugs with Narrow Therapeutic Index and the Phenomenon of Biocreep: A Critical Analysis of the System for Generic Substitution

Cited by 12 publications

References 76 publications

The efficacy and safety of cannabidiol as adjunct treatment for drug‐resistant idiopathic epilepsy in 51 dogs: A double‐blinded crossover study

The efficacy and safety of cannabidiol as adjunct treatment for drug‐resistant idiopathic epilepsy in 51 dogs: A double‐blinded crossover study

Lebanese pharmacists’ knowledge of generic drugs and factors affecting their use and selection following the pandemic and the economic crisis: A pilot cross-sectional study

A comprehensive review addressing the factors influencing generic drug substitution

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