Are generic formulations of carvedilol of inferior pharmaceutical quality compared with the branded formulation?
BACKGROUND
Carvedilol is a comprehensive beta(1)-, beta(2)-, and alpha(1)-adrenoreceptor blocker marketed as Dilatrend by F. Hoffmann-La Roche Ltd. (Roche) and as Coreg by GlaxoSmithKline for the treatment of hypertension, stable angina pectoris, post myocardial infarction with left ventricular dysfunction and all degrees of symptomatic chronic heart failure.


OBJECTIVE
In this report, the pharmaceutical qualities of Dilatrend 6.25 mg, 12.5 mg and 25 mg tablets and 35 randomly selected carvedilol generic products from 20 manufacturers in 19 countries have been assessed according to the European Pharmacopoeia and the Roche specifications.


METHODS
The generic products were subjected to four key tests: carvedilol content, tablet hardness, tablet dissolution and purity.


RESULTS
All three Dilatrend strengths conformed to specifications. At least 17/35 (48.6%) generic products failed the specifications due to: incorrect mean carvedilol content (outside 95-105%) - three products; excess impurities (> 0.3%) - one product; incorrect tablet hardness (outside 30-70 N) - 11 products; inadequate dissolution (< 75% in 30 min) - nine products. Seven products (20%) failed two tests, generally hardness and dissolution.


CONCLUSIONS
The dose-for-dose substitution of the original formulation of carvedilol (Dilatrend) with a pharmaceutically different, and possibly inferior, generic copy may conceivably result in a change in the efficacy of the treatment, because of an unanticipated change in pharmacokinetics or bioequivalence, and/or in a change in tolerability due to impurities.
Smith
Julian C
JC
Pharmaceutical Sciences, Aston University, Birmingham, UK. j.c.smith@aston.ac.uk
Tarocco
Giorgio
G
Merazzi
Fabio
F
Salzmann
Urs
U