Safety and tolerability of metoprolol OROS in hypertension treatment

Feliciano, Nancy; Kasarjian, P.H.; McMillen, James I.; Grau, Katharina; Kessler, Catherine; Stevelman, Harold; Hogan, Laura; Mroczek, William J.; Goldstein, Robert J.; Montoro, Rafael J.

doi:10.1016/0002-8703(90)90110-j

Cited by 3 publications

(2 citation statements)

References 9 publications

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“…73,84 In placebo controlled studies of atenolol, metoprolol CR, and pindolol, the edema rates for the ␤-blockers varied from 1.7% to 6% compared with 1.9% to 20% in the placebo groups. 23,24,59,111 A number of non-placebo-controlled studies of ␤-blockers have reported variable rates of edema: 1% to 6% for atenolol 25,43,60,72 ; 0% to 5% for metoprolol 35,36,59,112,113 ; 0% for carvedilol 45 ; 0% for pindolol 45 ; and 1% for dilevalol. 112 Two trials that lacked a placebo group documented lower extremity edema frequently in subjects treated with ␤-blockers.…”

Section: ␤-Blockersmentioning

confidence: 99%

Fluid Matters in Choosing Antihypertensive Therapy: A Hypothesis That the Data Speak Volumes

Blankfield

2005

The Journal of the American Board of Family Medicine

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Assuming that blood pressure is lowered equivalently, diuretics are more effective than angiotensinconverting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), and ␣-adrenergic receptor blockers (␣-blockers) at preventing heart failure, and they are more effective than ACEIs and ␣-blockers at preventing strokes. Compared with ␤-adrenergic receptor blockers (␤-blockers) and ACEIs, CCBs are less effective at reducing myocardial infarcts and heart failure. There is currently no conceptual framework by which to organize data indicating that some antihypertensive medications are better than others at preventing cardiovascular diseases. The thesis of this article is that the fluid reduction or fluid retention attributable to antihypertensive medications, either alone or in combination, provides a basis for ranking these medications. Diuretics have a theoretical advantage compared with other antihypertensive medications because they reduce total body fluid more than other agents. Therefore, they are the preferred drugs for treating hypertension. Provided that blood pressure is lowered comparably, diuretics have been demonstrated to be more effective than angiotensin-converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), and ␣-adrenergic receptor blockers (␣-blockers) at preventing heart failure, and diuretics have been found to be more effective than ACEIs and ␣-blockers at preventing stokes.

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Section: ␤-Blockersmentioning

confidence: 99%

Fluid Matters in Choosing Antihypertensive Therapy: A Hypothesis That the Data Speak Volumes

Blankfield

2005

The Journal of the American Board of Family Medicine

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“…2) and a metoprolol OROS oral osmotic pump system (Bauer et al 1990;Feliciano et al 1990;Kendall et al 1990;Plosker & Clissold 1992;Sandberg et al 1993). 2) and a metoprolol OROS oral osmotic pump system (Bauer et al 1990;Feliciano et al 1990;Kendall et al 1990;Plosker & Clissold 1992;Sandberg et al 1993).…”

Section: S Metoprololmentioning

confidence: 99%

Novel Oral Drug Formulations

Florence

Jani

1994

Drug Safety

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The rationale for specialised oral formulations of drugs include prolongation of effect for increased patient convenience and reduction of adverse effects through lowered peak plasma concentrations. Local and systemic adverse effects due to high concentrations of drug can be minimised by the use of controlled release delivery systems. Local effects in the gastrointestinal (GI) tract from the release of irritant drug molecules can also be reduced, but the gastric damage caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is only partially relieved by formulation approaches because of the involvement of systemic factors in the aetiology of GI adverse events. The advantages for each drug class must be examined. Newer dosage forms include: (i) osmotic pumps and zero order kinetics systems to control the release rate of the drug; (ii) bioadhesive systems and gastric retention devices to control GI transit; (iii) bioerodible hydrogels; (iv) molecular carrier systems (e.g. cyclodextrin-encapsulated drugs) to modulate local toxicity in the GI tract; (v) externally activated systems; and (vi) colloidal systems such as liposomes and microspheres. There is evidence for improved tolerability for a variety of drugs administered in novel delivery systems. However, the evidence for improved tolerability is complicated by the potential bias in adverse reaction reporting systems, and a lack of studies directly comparing conventional and modified release preparations. The technology now available to produce delivery systems which not only release drugs in a controlled and predetermined fashion, but which can also target to regions of the GI tract such as the colon, should allow greater control of therapy and potentially might minimise patient variables. However, the problem of variable GI transit times still eludes solution. Systems which rely on time to release drug might be more vulnerable to patient-to-patient variability than those which respond to local environments. The effect of food intake is more apparent on single-unit, nondisintegrating dosage forms, although of course none so far are immune from influence. The risk of new adverse effects resulting from such positional therapy with novel delivery devices must be considered. Understanding the mechanisms of induction of individual adverse effects can lead to advances in modes of delivery to decrease the potential for adverse reactions and events while maintaining therapeutic efficacy. Increased compliance can led to increased therapeutic control and hence safety. Each system has to be considered on its merits. No generalisations can be made, although invariably the modulation of high peak plasma concentrations diminishes adverse effects due to rapid absorption.

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Controlled Release Metoprolol Formulations

Plosker¹,

Clissold²

1992

Drugs

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Conventional formulations of metoprolol have become well established in cardiovascular medicine and are particularly useful in the management of hypertension and ischaemic heart disease. Recently developed controlled release metoprolol delivery systems (metoprolol CR/ZOK and metoprolol OROS) were designed to overcome the drug delivery problems of matrix-based sustained release forms by releasing the drug at a relatively constant rate over a 24-hour period, and thus producing sustained and consistent metoprolol plasma concentrations and beta 1-blockade while retaining the convenience of once daily administration. Clinically and statistically significant reductions in blood pressure have been observed with metoprolol CR/ZOK and metoprolol OROS 24 hours after administration in mildly or moderately hypertensive patients. Studies in patients with mild to moderate hypertension have demonstrated that a similar or higher percentage of patients achieved a goal response with metoprolol CR/ZOK compared with matrix-based sustained release formulations of metoprolol, or conventional atenolol or bisoprolol, while metoprolol OROS achieved an equal or greater response rate compared with conventional or matrix-based sustained release metoprolol preparations. In patients with stable effort angina pectoris, once daily administration of metoprolol CR/ZOK provided at least equal antianginal efficacy as conventional metoprolol in divided doses, while metoprolol OROS reduced the mean number of anginal attacks by the same margin as atenolol. Controlled release metoprolol formulations have been well tolerated in clinical trials. Metoprolol CR/ZOK was associated with a similar or lesser degree of adverse effects related to the central nervous system compared with atenolol or long acting propranolol. Metoprolol CR/ZOK also demonstrated less pronounced beta 2-mediated bronchoconstrictor effects than atenolol in asthmatics, and less general fatigue and leg fatigue in healthy subjects. Metoprolol OROS produced less pronounced bronchoconstrictor effects than atenolol, matrix-based sustained release metoprolol or long acting propranolol in patients with asthma or obstructive airways disease, and healthy volunteers. These results are presumably due to the beta 1-selectivity of metoprolol in addition to the relatively low plasma concentrations maintained by metoprolol CR/ZOK and metoprolol OROS, and the avoidance of high peak plasma concentrations with these agents. Despite the relative safety of the controlled release forms of metoprolol, the use of all beta-adrenoceptor antagonists should be avoided in patients with a history of bronchospasm. Thus, controlled release metoprolol formulations offer the potential to maximise the confirmed benefits of this agent in the management of hypertension and angina, by maintaining clinically effective plasma concentrations within a narrow therapeutic range over a 24-hour dose interval.

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Safety and tolerability of metoprolol OROS in hypertension treatment

Cited by 3 publications

References 9 publications

Fluid Matters in Choosing Antihypertensive Therapy: A Hypothesis That the Data Speak Volumes

Fluid Matters in Choosing Antihypertensive Therapy: A Hypothesis That the Data Speak Volumes

Novel Oral Drug Formulations

Controlled Release Metoprolol Formulations

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