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.
"Then the generic with a higher pharmacokinetic exposure (i.e. Cmax and AUC ratios that are higher than 100%), but still within the limits of bioequivalence, may not be able to guarantee the same therapeutic safety of the reference product   . "
[Show abstract][Hide abstract] ABSTRACT: When an innovative product (innovator) is not covered anymore by intellectual property rights, cheaper equivalent medicinal products (generic products) may be marketed and used in clinical practice. The regulation of generic products is well-established, and is primarily based on standard rules for quality, therapeutic equivalence requirements (the latter in most instances proven through a bioequivalence study), and safety data for the innovator. The extensive experience from bringing generic products to the market over the last decades allows the conclusion that they are well-accepted and provide a useful alternative option for cost-effective pharmacotherapy. While supporting this conclusion, there are a number of issues to be considered during the assessment of a generic product application. Six scenarios are described in total, from an efficacy and a safety perspective, where potential concerns with the current regulatory standards could arise in the approval of generic products. We also propose solutions to these scenarios in order to foster debate on these issues.
Scientia Pharmaceutica 12/2014; 82(4):847-56. DOI:10.3797/scipharm.1312-10
"There are very few available reports from either patients or physicians that address the question of generic drug-usage in PD from clinical perspectives . The majority of these data compared the original levodopa formulations to generic ones and demonstrated that the minority of patients (31%) did not tolerate generic formulations  . "
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to compare the efficacy of the branded and a generic extended-release ropinirole formulation in the treatment of advanced Parkinson’s disease (PD). Of 22 enrolled patients 21 completed the study. A rater blinded to treatment evaluated Unified Parkinson’s Disease Rating Scale, Fahn-Tolosa-Marin Tremor Rating Scale, Nonmotor Symptoms Assessment Scale, and a structured questionnaire on ropinirole side effects. Besides, the patients self-administered EQ-5D, Parkinson’s Disease Sleep Scale (PDSS-2), and Beck Depression Inventories. Branded and generic ropinirole treatment achieved similar scores on all tests measuring severity of motor symptoms (primary endpoint, UPDRS-III: 27.0 versus 28.0 points, ). Based on patient diaries, the lengths of “good time periods” were comparable (10.5 and 10.0 hours for branded and generic ropinirole, resp., ). However, generic ropinirole therapy achieved almost 3.0 hours shorter on time without dyskinesia (6.5 versus. 9.5 hours, ) and 2.5 hours longer on time with slight dyskinesia (3.5 versus. 1.0 hours, ) than the branded ropinirole did. Except for gastrointestinal problems, nonmotor symptoms were similarly controlled. Patients did not prefer either formulation. Although this study has to be interpreted with limitations, it demonstrated that both generic and branded ropinirole administration can achieve similar control on most symptoms of PD.
"Thus, even small variations in levodopa availability and consequently subtle fluctuations in levodopa blood levels can trigger motor complications. Since generic formulations differ from the branded product mainly in their excipients, which may affect absorption and bioavailability , simple bioequivalence cannot suffice to ensure comparable clinical efficacy and safety, especially in PD. "
[Show abstract][Hide abstract] 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.
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.
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.
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.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.