Are generic formulations of carvedilol of inferior pharmaceutical quality compared with the branded formulation?

ABSTRACT

Introduction: Carvedilol is a comprehensive β₁−, β2− and α₁-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.

Objectives: 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.

Conclusion: 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.

Key words: :

• Carvedilol
• Content
• Dissolution
• Generics
• Purity
• Quality
• Tablet hardness

Notes

* Data from this paper were presented at the Malaysian Pharmaceutical Society Pharmacy Scientific Conference, November 2005, Kuala Lumpur, Malaysia