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(R) / Prolopa(R) 125, Roche, Switzerland) in order to
evaluate the potential impact of Madopar(R) generics versus branded products for PD patients and clinicians.
METHODS:
Madopar(R)
/ Prolopa(R) 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(R)/Prolopa(R), and also invite to further investigations in
view of a more comprehensive approach, both pharmaceutical and clinical.
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