Article

Generic versus branded pharmacotherapy in Parkinson's disease: Does it matter? A review

Department of Neurology, University of Florida, McKnight Brain Institute, Movement Disorders Center, 100 S. Newell Drive, Gainesville, FL 32611, USA.
Parkinsonism & Related Disorders (Impact Factor: 4.13). 02/2011; 17(5):308-12. DOI: 10.1016/j.parkreldis.2011.02.005
Source: PubMed

ABSTRACT There is an ongoing debate about generic drug use for a multitude of conditions including epilepsy, psychosis, hypertension, post-organ transplantation, and several infectious diseases. Most of the concerns involve drugs with narrow therapeutic indices. There is a heightened attention to health care costs and macroeconomic policy as well as microeconomic business decisions that may impact the use of generic drugs. The issues surrounding generic substitution for chronic degenerative conditions such as in Parkinson's disease (PD) continue to be controversial subjects for physicians, pharmacists, patients, Medicare/governmental insurance programs, and for private insurance companies. The United States Food and Drug Administration (FDA) requires that generic drugs meet a standard for bioequivalence prior to market approval, but this may not translate to therapeutic efficacy or to overall patient tolerance. In this review we will address issues related to the use of generics versus branded drugs in PD, and the potential impact substitution of generics may have on patients and on clinicians. Having proper documentation may help in deciding the appropriate usage of these drugs in PD. Medicare, governmental run health care systems, and third party insurance companies should in a complex disease such as PD, allow physicians and patients the chance to properly document the superiority of brand versus generic approaches. Currently, in the U.S, and in many countries around the world, there is no obligation for payers to respect these types of patient specific bedside trials, and there has been no standardization of the process.

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    ABSTRACT: Stehen zur Parkinson Behandlung zwei oder mehrere Substanzen „essentieller Ähnlichkeit“ zur Verfügung, ist aufgrund des Wirtschaftlichkeitsgebotes das preisgünstigste Produkt zu verordnen. Für ein Generikum müssen Wirkstoff, Wirkstärke, Darreichungsform und Bioverfügbarkeit vergleichbar zum Orginalprodukt sein. Die Bioäquivalenz wird als nachgewiesen angesehen, wenn nach Gabe einer Einzeldosis bei einer kleinen Anzahl gesunder Probanden die „area under the curve“ (AUC) und die maximale Plasmakonzentration (Cmax) mit ihrem 90%igen Konfidenzintervall in einem Bereich von 80 bis 125% des Orginalproduktes liegen. Es ist problematisch, hieraus eine dem Orginalprodukt äquivalente Wirkung und Verträglichkeit des Generikums bei Parkinson Patienten abzuleiten, ohne dass Untersuchungen an Patienten vorliegen müssen. Die zulässige Schwankungsbreite in der Bioverfügbarkeit kann ferner bei Produktwechsel zu Wirkungs- und Verträglichkeitsproblemen führen. Die Verordnung von Generika mit wechselnd aussehenden Tabletten und der mit der Einnahme günstigerer Produkte assoziierte Nocebo Effekt verringern die Therapieadhärenz bei Patienten und Caregivern. Eine Aufklärung der Patienten über Wirkungen und Nebenwirkungen des Generikums ist nicht möglich, da keine Patientendaten vorliegen. Auch weiß der Verordner nicht, welches Generikum in der Apotheke ausgehändigt wird. Daraus eröffnen sich für den Arzt neue und ggf. wechselnde Haftungsmöglichkeiten. Vorgeschlagen wird, die Kontinuität mit Verordnung desselben Produktes zu wahren und bei Zweifeln an der Substitutionsfähigkeit eines Medikamentes „aut idem“ anzukreuzen. Wirkung und Nebenwirkungen der Generika sollten dokumentiert und ein Produktwechsel als potentielle Ursache für eine plötzliche klinische Verschlechterung in Betracht gezogen werden. Zulassungsstudien für Generika zur Parkinson Therapie an Patienten erscheinen notwendig. Cost effectiveness formalities demand to prescribe the lowest priced product when availability of two or more drugs with essential similarity is given. Generic drugs containing the same active substance are considered bioequivalent if they are pharmaceutically equivalent and their bioavailabilities after administration in the same molar dose lie within acceptable predefined limits. Bioequivalence is assumed, if after a single dose in a small number of healthy subjects the 90% confidence interval of the plasma parameters ’area under the curve’ (AUC) and peak concentration (Cmax) for the ratio of the test and reference products are contained within the acceptance interval of 80-125%. Herefrom equivalent efficacy and tolerability compared to the reference product is derived for Parkinson patients without patient studies. The accepted large limits of bioequivalence variation might lead to reduced efficacy and tolerability in Parkinson patients. Changing appearance of tablets and nocebo effects related to the intake of a lower priced product reduce adherence in patients and caregivers. The physician can not give proper medical product information to the patient due to lack of generic drug studies in Parkinson´s disease. Furthermore physicians do not know which generic drug the patient will receive at the pharmacy. This leads for prescribers to new and possibly changing liabilities for consequences. We suggest continuity in prescribing a product and to tick off ’aut idem’ if there is concern about exchangeability of a product. Efficacy and adverse events of generic pharmaceutics should be documented. A product change has to be considered as a potential reason for clinical deterioration. Studies in patients are demanded for generic drug approval for treatment of Parkinson´s disease.
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    ABSTRACT: Background By definition, a generic product is considered interchangeable with the innovator brand product. Controversy exists about interchangeability, and attention is predominantly directed to contaminants. In particular for chronic, degenerative conditions such as in Parkinson’s disease (PD) generic substitution remains debated among physicians, patients and pharmacists. The objective of this study was to compare the pharmaceutical quality of seven generic levodopa/benserazide hydrochloride combination products marketed in Germany with the original product (Madopar® / Prolopa® 125, Roche, Switzerland) in order to evaluate the potential impact of Madopar® generics versus branded products for PD patients and clinicians. Methods Madopar® / Prolopa® 125 tablets and capsules were used as reference material. The generic products tested (all 100 mg/25 mg formulations) included four tablet and three capsule formulations. Colour, appearance of powder (capsules), disintegration and dissolution, mass of tablets and fill mass of capsules, content, identity and amounts of impurities were assessed along with standard physical and chemical laboratory tests developed and routinely practiced at Roche facilities. Results were compared to the original “shelf-life” specifications in use by Roche. Results Each of the seven generic products had one or two parameters outside the specifications. Deviations for the active ingredients ranged from +8.4% (benserazide) to −7.6% (levodopa) in two tablet formulations. Degradation products were measured in marked excess (+26.5%) in one capsule formulation. Disintegration time and dissolution for levodopa and benserazide hydrochloride at 30 min were within specifications for all seven generic samples analysed, however with some outliers. Conclusions Deviations for the active ingredients may go unnoticed by a new user of the generic product, but may entail clinical consequences when switching from original to generic during a long-term therapy. Degradation products may pose a safety concern. Our results should prompt caution when prescribing a generic of Madopar®/Prolopa®, and also invite to further investigations in view of a more comprehensive approach, both pharmaceutical and clinical.
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