Circadian Rhythm and Blood Pressure

  • A multicenter, randomized, double-blind, double-dummy, blind-endpoint crossover study (n=41) compared InnoPran XL® and non-chronotherapeutic propranolol ER

    – Similar improvements in mean 24-hour BP (systolic and diastolic) were observed in both groups*10

    BP and HR Reductions From 6:00 AM to Noon: InnoPran XL® vs propranolol ER in Beta-Blocker–Sensitive Patients10

    Results shown are from beta-blocker–sensitive patients (n=11). Beta-blocker–sensitive patients were defined as the 25% of patients with the greatest reduction in diastolic BP between 6:00 AM and noon. In this study, patients received equivalent 120-mg doses of each study medication.10

    *Systolic/diastolic BP changes were -9.0/-6.9 mm Hg InnoPran XL® and -10.4/-7.7 mm Hg propranolol ER. P=not significant.

    †Double product=systolic BP x HR. Double product is a key measure of cardiac workload.

    ††Difference in diastolic blood pressure InnoPran XL vs propranolol ER was significant (P<.04).

    Reference:

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

  • InnoPran XL® provided a 50% improvement in double-product relative to propranolol ER10

The Morning Risk Zone1,2

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

[Adapted from Elliott 2001]

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.

InnoPran XL® vs Non-chronotherapeutic Propranolol ER

  • Compared to non-chronotherapeutic propranolol (propranolol extended release [ER]), the release profile of InnoPran XL® provides full 24-hour control with peak blood levels during the AM hours6,10

  • Lower serum levels in the PM hours may have less effect on HR during waking hours

    Propranolol Blood Concentrations During the Morning Risk Zone

    (InnoPran XL® vs Non-chronotherapeutic Propranolol ER)10

    References:

    6. InnoPran XL® (propranolol hydrochloride) [package insert]. Baudette, MN: ANI Pharmaceuticals, Inc.; 2017.

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

  • Data from a double-blind crossover study comparing InnoPran XL administered at 10:00 pm vs propranolol ER administered at 8:00 am (N=41)10

InnoPran XL® – A Different Formulation

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

Timed-Release Design Targets the Morning Risk Zone7a

Reference:

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.

Pivotal Study Adverse Reactions

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

Most Common Adverse Reactions in Pivotal Study

In the pivotal clinical trial for InnoPran 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.

Medical Information Requests

Healthcare Providers who have questions about InnoPran 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

In Hypertension, InnoPran XL® is Designed to… Take on the Surge1,2

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. InnoPran 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. Learn here how one bedtime dose of InnoPran XL® can help your patients Take on the Surge and manage their hypertension for a full 24 hours.

References:

1. Muller JE. Circadian variation and triggering of acute coronary events. Am Heart J. 1999;137(4 pt 2):S1-S8.

2. Elliot WJ. Cyclic and circadian variations in cardiovascular events. Am J Hypertens. 2001;14(9 pt 2):291S-295S.

INDICATION: InnoPran XL® is a beta adrenergic blocker indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions.

LIMITATION OF USE: InnoPran XL® is not indicated for the treatment of hypertensive emergencies.

Important Safety Information

WARNING: CARDIAC ISCHEMIA AFTER ABRUPT DISCONTINUATION

Following abrupt discontinuation of therapy with beta-blockers, exacerbations of angina pectoris and myocardial infarction have occurred.

When discontinuing chronically administered InnoPran XL®, particularly in patients with ischemic heart disease, gradually reduce the dose over a period of 1-2 weeks and monitor the patients. If angina markedly worsens or acute coronary insufficiency develops, promptly resume therapy, at least temporarily and take other measures appropriate for the management of unstable angina. Warn patients against interruption or discontinuation of therapy without physician’s advice.

Because coronary artery disease is common and may be unrecognized, avoid abrupt discontinuation of InnoPran XL® therapy even in patients treated only for hypertension.

Contraindications

InnoPran XL® is contraindicated in patients with cardiogenic shock or decompensated heart failure; sinus bradycardia, sick sinus syndrome, and greater than first-degree block unless a permanent pacemaker is in place; bronchial asthma; and known hypersensitivity (e.g., anaphylactic reaction) to propranolol hydrochloride or any of the components of InnoPran XL®.

Warnings And Precautions

Cardiac Failure: Beta-blockers, like InnoPran XL®, can cause depression of myocardial contractility and may precipitate heart failure and cardiogenic shock. If signs or symptoms of heart failure develop, treat the patient according to recommended guidelines. It may be necessary to lower the dose of InnoPran XL® or to discontinue it.

Maintain During Major Surgery: Chronically administered beta-blocking therapy, including InnoPran XL®, should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.

Masked Signs of Hypoglycemia: Beta-blockers, like InnoPran XL®, may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be significantly affected.

Thyrotoxicosis: InnoPran XL® may mask clinical signs of hyperthyroidism, such as tachycardia. Avoid abrupt withdrawal of beta-blockade, which may precipitate a thyroid storm.

Bradycardia: Bradycardia, including sinus pause, heart block, and cardiac arrest have occurred with the use of InnoPran XL®. Patients with first-degree atrioventricular block, sinus node dysfunction, or conduction disorders (including Wolff-Parkinson-White) may be at increased risk. The concomitant use of beta adrenergic blockers and non-dihydropyridine calcium channel blockers (e.g., verapamil and diltiazem), digoxin or clonidine increases the risk of significant bradycardia. Monitor heart rate and rhythm in patients receiving InnoPran XL®. If severe bradycardia develops, reduce or stop InnoPran XL®.

Reduced Effectiveness of Epinephrine in Treating Anaphylaxis: Beta adrenergic blocker-treated patients treated with epinephrine for a severe anaphylactic reaction may be less responsive to the typical doses of epinephrine. In these patients, consider other medications (e.g., intravenous fluids, glucagon).

Adverse Reactions

The most commonly reported adverse reactions (≥3% and greater than placebo) included the following: fatigue, dizziness, and constipation.

You are encouraged to report negative side effects of prescription drugs to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch or ANI Pharmaceuticals, Inc. at 1-800-308-6755.

Click here for Full Prescribing Information including Black Box Warning.

InnoPran XL® is a registered trademark of ANI Pharmaceuticals, Inc. Marketed and distributed by: ANI Pharmaceuticals, Inc.
InnoPran XL®, a DIFFUCAPS® drug delivery product manufactured by Adare Pharmaceuticals, Inc., Vandalia, OH 45377
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Developed April, 2017

*Terms and conditions

Offer not valid for any individual for whom any part of InnoPran XL® prescription is or will be covered by Medicaid, Medicare (including Medicare Advantage or Part D Prescription Plans), any state prescription drug programs, or any other public payer program.

  • This program cannot be combined with any other coupon certificate, voucher or similar offer.
  • Offer applies to out-of-pocket (OOP) expenses for InnoPran XL®. Out-of-pocket expenses greater than $0 will be covered up to a maximum of $300 per prescription of actual out-of-pocket expenses (a) per 30-day supply for each of up to twelve (12) prescription fills, (b) per 60-day supply for each of up to six (6) prescription fills, or (c) per 90-day supply for each of up to four (4) prescription fills.
  • Offer good only in the USA and Puerto Rico at participating retail pharmacies and cannot be redeemed at government-subsidized clinics.
  • ANI Pharmaceuticals, Inc. reserves the right to rescind, revoke or amend this offer without notice.
  • Participation in this program must comply with all applicable state laws and contractual or other obligations as a pharmacy provider.
  • This is not an insurance program.
  • Participating patients and pharmacists understand and agree to comply with the terms and conditions of this offer as set forth herein.
  • Offer not extended for prescriptions for:
    • No claims paid by Government-sponsored insurance plans
      • Medicare, Medicaid, Federal, State, Patient Pharmaceutical Assistance
    • No Pharmacies in states that prohibit the offering of co-pay assistance at the point of dispensing
    • Patients 17 years of age and younger are excluded
    • No cash claims

To find a participating eVoucherRx™ pharmacy visit: www.evoucherrx.relayhealth.com/storelookup.

For questions about the copay card program or if you have problems processing the copay card please call 1-888-846-0234.