February 2003

Cardiovascular Agents

Imdur (isosorbide mononitrate) Extended-Release Tablets

Manufacturer: Schering Corporation

Drug Approval Classification: Supplemental NDA (approval date: 1/22/03)

Clinical Summary: A "Geriatric Use" section was added to the Imdur (isosorbide mononitrate) product labeling. It states the following:

Geriatric Use: Clinical studies of Imdur tablets did not include sufficient information on patients age 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience for Imdur has not identified differences in response between elderly and younger patients. Clinical experience for organic nitrates reported in the literature identified a potential for severe hypotension and increased sensitivity to nitrates in the elderly.

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Elderly patients may have reduced baroreceptor function and may develop severe orthostatic hypotension when vasodilators are used. Imdur should therefore be used with caution in elderly patients who may be volume depleted, on multiple medications, or who, for whatever reason, are already hypotensive. Hypotension induced by isosorbide mononitrate may be accompanied by paradoxical bradycardia and increased angina pectoris.

Elderly patients may be more susceptible to hypotension and may be at a greater risk of falling at therapeutic doses of nitroglycerin.

Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy, particularly in the elderly.

Imdur (isosorbide mononitrate) Extended Release Tablets Letter

Imdur (isosorbide mononitrate) Extended Release Tablets

Tenormin (atenolol) Tablets

Manufacturer: AstraZeneca Pharmaceuticals LP

Drug Approval Classification: Supplemental NDA (approval date: 1/9/03)

Clinical Summary: This supplemental NDA provides for 3 changes to the product labeling.

Geriatric Use

Hypertension and angina pectoris due to coronary atherosclerosis:

-- Clinical studies of Tenormin did not include a sufficient number of patients aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Acute myocardial infarction:

-- Of the 8037 patients with suspected acute myocardial infarction randomized to Tenormin in the ISIS-1 trial, 33% (2644) were 65 years of age and older. It was not possible to identify significant differences in efficacy and safety between older and younger patients; however, elderly patients with systolic blood pressure < 120 mmHg seemed less likely to benefit.

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Evaluation of patients with hypertension or myocardial infarction should always include assessment of renal function.

The following was added to the Clinical Pharmacology section of the product labeling:

In general, elderly patients present higher atenolol plasma levels with total clearance values about 50% lower than younger subjects. The half-life is markedly longer in the elderly compared with younger subjects. The reduction in atenolol clearance follows the general trend that the elimination of renally excreted drugs is decreased with increasing age.

Dosing: New dosing information for the elderly was changed to include wording that dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Evaluation of patients with hypertension or myocardial infarction should always include assessment of renal function.

Tenormin (atenolol) Letter

Tenormin (atenolol)

Medscape Pharmacists. 2003;4(1) © 2003 Medscape

Cite this: February 2003 - Medscape - Feb 20, 2003.