Drugs Becoming Generics—The Impact of Genericization on the Market Performance of Antihypertensive Active Pharmaceutical Ingredients

Abstract

To explore long-term changes in intra and inter-class choices between generic compounds, this paper investigates the market trends of two antihypertensive drug classes that have closely related pharmacological mechanisms—angiotensin convertase enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). We analysed the development of ACEI and ARB markets between 2001 and 2016 in nine European countries, covering the genericization transition periods of both therapeutic groups. The analysis was undertaken on the level of the active pharmaceutical ingredients (API) and focused on international and country-specific diffusion patterns. Comparison of ARB and ACEI therapies shows that although ARBs became off-patent during the observed period, and have a clinical advantage in terms of the adverse event profile over ACEIs, the increasing dominance of ARBs cannot be identified. One explanation is that ACEI therapies became generics earlier, relocating competition to the level of brands, while competition among ARBs remained at the level of the APIs. As for intra-class drug preferences, it was observed that the long-term trends show that ramipril outperformed its ACEI competitors, even though the kinetics and the rank order of preferred active compounds were inconsistent among markets. The diffusion of clinically preferable therapies seems to be ultimately supported by generic entries. In Eastern European countries, the emergence of generic markets has not only improved access to ACE inhibitors and ARBs, but has been a prerequisite for changing preferences. In contrast, genericization resulted in the relative anchoring of prior, branded era-based preferences in some Western European countries, which may be attributed to the role of the cessation of promotion and the fixity of prescription behaviour.

Impact of ramipril nitroso-metabolites on cancer incidence — in silico and in vitro safety evaluation

“…Angiotensin-converting enzyme inhibitors (ACE-Is) are a valuable class of drugs with well-established use as a first-line option in cardiovascular and renal system related diseases. Their pharmacological background translates into their high prevalence and wide-spread use [ 1 ], with ramipril (RAM) holding one of the highest market shares in Europe [ 2 ]. Despite the unquestionable on-target efficiency, there are accumulating reports suggesting serious off-target toxicity of these drugs.…”

“…For all these reasons, in the present pilot study, we intended to verify whether ACE-Is could form mutagenic nitroso-metabolites following drug administration. We selected RAM as a model ACE-I based on its prevalence of use and its chemical properties [ 2 ]. In fact, RAM is a 2-methylpropionyl-L-proline derivative with an unsubstituted nitrogen atom available for interaction with nitrite [ 26 ].…”