f cardiac disease, and should receive further cardiac eva luation if findings suggest such disease (e.g., electrocardiogram and echocardiogram). Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during atomoxetine treatment should undergo a prompt cardiac eva luation.
5.4 Effects on Blood Pressure and Heart Rate
STRATTERA should be used with caution in patients whose underlying medical conditions could be worsened by increases in blood pressure or heart rate such as certain patients with hypertension, tachycardia, or cardiovascular or cerebrovascular disease. It should not be used in patients with severe cardiac or vascular disorders whose condition would be expected to deteriorate if they experienced clinically important increases in blood pressure or heart rate [see Contraindications (4.5)]. Pulse and blood pressure should be measured at baseline, following STRATTERA dose increases, and periodically while on therapy to detect possible clinically important increases.
The following table provides short-term, placebo-controlled clinical trial data for the proportions of patients having an increase in: diastolic blood pressure ≥15 mm Hg; systolic blood pressure ≥20 mm Hg; heart rate greater than or equal to 20 bpm, in both the pediatric and adult populations (see TABLE 1).
Table 1a
a Abbreviations: bpm=beats per minute; DBP=diastolic blood pressure; HR=heart rate; mm Hg=millimeters mercury; SBP=systolic blood pressure.
b Proportion of patients meeting threshold at any one time during clinical trial.
Pediatric Acute
Placebo-Controlled Adult Acute
Placebo-Controlled
Maximumb Endpoint Maximumb Endpoint
Atomoxetine Placebo Atomoxetine Placebo Atomoxetine Placebo Atomoxetine Placebo
% % % % % % % %
DBP
(≥15 mm Hg) 21.5 14.1 9.3 4.8 12.6 8.7 4.8 3.5
SBP
(≥20 mm Hg) 12.5 8.7 4.9 3.3 12.4 7.8 4.2 3.2
HR
(≥20 bpm) 23.4 11.5 12.2 3.8 22.4 8.3 10.2 2.0
In placebo-controlled registration studies involving pediatric patients, tachycardia was identified as an adverse event for 0.3% (5/1597) of these STRATTERA patients compared with 0% (0/934) of placebo patients. The mean heart rate increase in extensive metabolizer (EM) patients was 5.0 beats/minute, and in poor metabolizer (PM) patients 9.4 beats/minute.
In adult clinical trials where EM/PM status was available, the mean heart rate increase in PM patients was significantly higher than in EM patients (11 beats/minute versus 7.5 beats/minute). The heart rate effects could be clinically important in some PM patients.
In placebo-controlled registration studies involving adult patients, tachycardia was identified as an adverse event for 1.5% (8/540) of STRATTERA patients compared with 0.5% (2/402) of placebo patients.
In adult clinical trials where EM/PM status was available, the mean change from baseline in diastolic blood pressure in PM patients was higher than in EM patients (4.21 versus 2.13 mm Hg) as was the mean change from baseline in systolic blood pressure (PM: 2.75 versus EM: 2.40 mm Hg). The blood pressure effects could be clinically impo
