Studies have demonstrated that blood pressure rises and falls at different times of the day. In general, blood pressure and heart rate will be lower while sleeping and will rise upon awakening and assuming a prone position. This circadian fluctuation in blood pressure has been noted in the scientific literature for decades.

Propranolol Blood Concentrations During the Vital Morning Hours
(Non-chronotherapeutic Propranolol ER)

Data from a double-blind crossover study comparing INDERAL® XL administered at 10:00 pm vs Propranolol ER administered at 8:00 am (n=41)7a

Example of BP and HR elevation upon awakening adapted from Mancia G et al.Hypertens.1983;5:573-5787b

References:

6. Neutel JM, Schnaper H, Cheung DG, et al. Antihypertensive effects of β-blockers administered once daily: 24-hour measurements. Am Heart J. 1990;120:166-171.

7a. Neutel JM, Rotenberg K. Comparison of a chronotherapeutically administered β blocker vs. a traditionally administered β blocker in patients with hypertension. J Clin Hypertens (Greenwich). 2005;7:395-400.

7b. Mancia G, Ferrari A, Pomidossi G, et al. Twenty-four‐hour‐hemodynamic profile during treatment of essential hypertension by once-a-day nadolol. Hypertens. 1983;5:573-578.

For patients with hypertension, rapid surges in morning blood pressure can cause problems. Morning surges in blood pressure have been associated with increased incidence of heart attack, stroke and other cardiovascular events. For this reason, the early morning hours are sometimes referred to as the Morning Risk Zone, a period of time when your patients may be at greater risk.

Elevation of Stroke and MI Upon Awakening2

References:

1. Muller JE. Circadian variation and triggering of acute coronary events. Am Heart J. 1999;137:S1-S8.

2. Elliott WJ. Cyclic and circadian variations in cardiovascular events. Am J Hypertens. 2001;14:291S-295S.

INDERAL® XL is a circadian-aligned formulation of propranolol. Its ability to deliver antihypertensive effects in the morning lies in its proprietary drug release technology. INDERAL® XL is formulated to take on dangerous morning surges in blood pressure and to control blood pressure for a full 24 hours.

Advanced Time-release Formulation of Propranolol
Targets the Vital Morning Hours

References:

7a. Neutel JM, Rotenberg K. Comparison of a chronotherapeutically administered β blocker vs. a traditionally administered β blocker in patients with hypertension. J Clin Hypertens (Greenwich). 2005;7:395-400.

Adverse reactions occurring in ≥3% of subjects and at greater incidence than placebo during double-blind treatment with INDERAL® XL and plausibly related to treatment.

Most Common Adverse Reactions in Pivotal Study

In the pivotal clinical trial for INDERAL® XL, doses above 120 mg had no additional effect on BP.

*Dizziness excludes vertigo.

Please see additional safety information in Important Safety Information and Full Prescribing Information.

Healthcare Providers who have questions about INDERAL® XL may request clinical information at 1-800-308-6755 or drugsafety@anipharmaceuticals.com.

To report SUSPECTED ADVERSE REACTIONS, contact ANI Pharmaceuticals, Inc. at 1-800-308-6755 or drugsafety@anipharmaceuticals.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

For materials or more information, please visit www.anipharmaceuticals.com

INDERAL® XL: A Different Blood Pressure Medicine

Blood pressure and heart rate surge in the morning hours (6 am-12 pm). Clinical studies have demonstrated an increase in the risk of MI and stroke during this same time period, known as the Morning Risk Zone. INDERAL® XL is a circadian-aligned, beta-blocker therapy that helps to reduce the risk of cardiovascular events such as MI and stroke during the Morning Risk Zone.

INDERAL® XL is designed to reach its peak effect in the early morning hours so that it can control the circadian-influenced surge in morning blood pressure. When patients take INDERAL® XL at bedtime — around 10 pm is recommended — they get a medication that delivers antihypertensive effects in the morning. And because INDERAL® XL is a timed-release medication, it will keep working for 24 hours to keep your patient’s blood pressure under control all day.

INDERAL® XL Lowered Systolic and Diastolic BP in the Morning and Evening

BP Measured in the Morning
(6:00 am – 10:00 am)8

When measured in the morning, reductions in systolic and diastolic BP in the placebo group were -8.19 mm Hg and -6.98 mm Hg, respectively.

BP Measured in the Evening
(5:30 pm – 6:30 pm)8

When measured in the evening, reductions in systolic and diastolic BP in the placebo group were -7.62 mm Hg and -7.76 mm Hg, respectively.

Data shown are for INDERAL® XL 80 mg. Similar results were observed using 120 mg.

References:

8. Sica DA, Neutel JM, Weber MA, et al. The antihypertensive efficacy and safety of a chronotherapeutic formulation of propranolol in patients with hypertension. J Clin Hypertens (Greenwich). 2004;6:231-241.