Edarbi

Dosing Form & Strengths

tablet

• 40mg
• 80mg

Hypertension

Indicated for hypertension, either alone or in combination with other antihypertensives

80 mg PO qDay

Coadministration with high-dose diuretics: 40 mg PO qDay

Renal Impairment

No dose adjustment is required with mild-to-severe renal impairment or end-stage renal disease

Patients with moderate-to-severe renal impairment are more likely to report high serum creatinine values

Hepatic Impairment

Dose adjustment not necessary with mild-to-moderate hepatic impairment; monitor in severe impairment (data not available)

Administration

May be administered with or without food

Safety and efficacy not established

No dose adjustment is necessary in elderly patients

Abnormally high serum creatinine values were more likely to be reported for patients aged 75 or older

Hypertension

80 mg PO qDay

Coadministration with high-dose diuretics: 40 mg PO qDay

Pregnancy Category: C (1st trimester); D (2nd and 3rd trimesters)

Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system causing oligohydramnios, which may result in fetal injury and/or death

Lactation: unknown whether distributed in breast milk, decide on alternate antihypertensive therapy or do not breastfeed

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Contact your doctor right away if you become pregnant while taking Edarbi. See "Pregnancy" and "FDA Warning" sections for more information.

Edarbi can cause very low blood pressure leading to dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. This is more commonly seen at the beginning of therapy in people who take diuretics, or in people on dialysis. Diarrhea, vomiting, not drinking enough fluids, and sweating can cause a decrease in blood pressure and can lead to lightheadedness and fainting. Tell your doctor if you have any of these problems during your treatment. 

• Avoid getting up too fast from a sitting or lying position.
• Get up slowly and prevent falls by steadying yourself.
• Do not drive or operate heavy machinery until you know how Edarbi affects you.
• Limit alcoholic beverages.

Your doctor may monitor your kidney function if you are elderly, have kidney disease, have severe congestive heart failure (CHF) or if you are taking nonsteroidal anti-inflammatory drugs, as Edarbi may cause a decrease in kidney function.

Do not use potassium supplements or salt substitutes while you are receiving Edarbi, unless your doctor instructs you to.

• Store Edarbi at room temperature between 59°F to 86°F (15°C to 30°C).
• Store Edarbi in the original container that you received from your pharmacist or doctor. Do not put Edarbi into a different container.
• Keep Edarbi in a tightly closed container, and keep Edarbi out of the light.
• Keep Edarbi and all medicines out of the reach of children.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Edarbi is an angiotensin II receptor blocker (ARB) indicated for the treatment of hypertension to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including the class to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with Edarbi.

Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).

Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.

Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.

Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.

Edarbi may be used alone or in combination with other antihypertensive agents.

Recommended Dose

The recommended dose in adults is 80 mg taken orally once daily. Consider a starting dose of 40 mg for patients who are treated with high doses of diuretics.

If blood pressure is not controlled with Edarbi alone, additional blood pressure reduction can be achieved by taking Edarbi with other antihypertensive agents.

Edarbi may be taken with or without food [see Clinical Pharmacology (12.3)].

Handling Instructions

Do not repackage Edarbi. Dispense and store Edarbi in its original container to protect Edarbi from light and moisture.

Special Populations

No initial dose adjustment is recommended for elderly patients, patients with mild-to-severe renal impairment, end-stage renal disease, or mild-to-moderate hepatic dysfunction. Edarbi has not been studied in patients with severe hepatic impairment [see Clinical Pharmacology (12.3)].

Pregnancy

Pregnancy Category D

Use of drugs that affect the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Edarbi as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.

In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue Edarbi, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to Edarbi for hypotension, oliguria, and hyperkalemia [see Use in Specific Populations (8.4)].

Nursing Mothers

It is not known if azilsartan is excreted in human milk, but azilsartan is excreted at low concentrations in the milk of lactating rats. Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Neonates with a history of in utero exposure to Edarbi

If oliguria or hypotension occurs, support blood pressure and renal function. Exchange transfusions or dialysis may be required.

Safety and effectiveness in pediatric patients under 18 years of age have not been established.

Geriatric Use

No dose adjustment with Edarbi is necessary in elderly patients. Of the total patients in clinical studies with Edarbi, 26% were elderly (65 years of age and older); 5% were 75 years of age and older. Abnormally high serum creatinine values were more likely to be reported for patients age 75 or older. No other differences in safety or effectiveness were observed between elderly patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see Clinical Pharmacology (12.3)].

Renal Impairment

Dose adjustment is not required in patients with mild-to-severe renal impairment or end-stage renal disease. Patients with moderate to severe renal impairment are more likely to report abnormally high serum creatinine values.

Hepatic Impairment

No dose adjustment is necessary for subjects with mild or moderate hepatic impairment. Edarbi has not been studied in patients with severe hepatic impairment [see Clinical Pharmacology (12.3)].

The antihypertensive effects of Edarbi have been demonstrated in a total of seven double-blind, randomized studies, which included five placebo-controlled and four active comparator-controlled studies (not mutually exclusive). The studies ranged from six weeks to six months in duration, at doses ranging from 20 mg to 80 mg once daily. A total of 5941 patients (3672 given Edarbi, 801 given placebo, and 1468 given active comparator) with mild, moderate or severe hypertension were studied. Overall, 51% of patients were male and 26% were 65 years or older; 67% were white and 19% were black.

Two 6-week, randomized, double-blind studies compared the effect on blood pressure of Edarbi at doses of 40 mg and 80 mg, with placebo and with active comparators. Blood pressure reductions compared to placebo based on clinic blood pressure measurements at trough and 24-hour mean blood pressure by ambulatory blood pressure monitoring (ABPM) are shown in Table 1 for both studies. Edarbi, 80 mg, was statistically superior to placebo and active comparators for both clinic and 24-hour mean blood pressure measurements.

In a study comparing Edarbi to valsartan over 24 weeks, similar results were observed.

Most of the antihypertensive effect occurs within the first two weeks of dosing.

Figure 2 shows the 24-hour ambulatory systolic and diastolic blood pressure profiles at endpoint.

Other studies showed similar 24-hour ambulatory blood pressure profiles.

Edarbi has a sustained and consistent antihypertensive effect during long-term treatment, as shown in a study that randomized patients to placebo or continued Edarbi after 26 weeks. No rebound effect was observed following the abrupt cessation of Edarbi therapy.

Edarbi was effective in reducing blood pressure regardless of the age, gender, or race of patients, but the effect, as monotherapy, was smaller, approximately half, in black patients, who tend to have low renin levels. This has been generally true for other angiotensin II antagonists and ACE inhibitors.

Edarbi has about its usual blood pressure lowering effect size when added to a calcium channel blocker (amlodipine) or a thiazide-type diuretic (chlorthalidone).

There are no trials of Edarbi demonstrating reductions in cardiovascular risk in patients with hypertension, but at least one pharmacologically similar drug has demonstrated such benefits.

See FDA-approved patient labeling (17.2).

General Information

Pregnancy

Tell female patients of childbearing potential about the consequences of exposure to Edarbi during pregnancy. Discuss treatment options with women planning to become pregnant. Tell patients to report pregnancies to their physicians as soon as possible.

FDA-Approved Patient Labeling

Patient Information
Edarbi (eh-DAR-bee)
(azilsartan medoxomil)
Tablets

Read this Patient Information leaflet before you start taking Edarbi and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment.

What is the most important information I should know about Edarbi?

• Edarbi can cause harm or death to your unborn baby.
• Talk to your doctor about other ways to lower your blood pressure if you plan to become pregnant.
• If you become pregnant while taking Edarbi, tell your doctor right away. Your doctor may switch you to a different medicine to treat your high blood pressure.

What is Edarbi?

Edarbi is a prescription medicine called an angiotensin II receptor blocker (ARB) used to treat high blood pressure (hypertension) in adults.

Your doctor may prescribe other medicines for you to take along with Edarbi to treat your high blood pressure.

It is not known if Edarbi is safe and effective in children under 18 years of age.

What should I tell my doctor before taking Edarbi?

Before you take Edarbi, tell your doctor if you:

• have been told that you have abnormal body salt (electrolytes) levels in your blood
• are pregnant or plan to become pregnant. See "What is the most important information I should know about Edarbi?"
• are breastfeeding or plan to breastfeed. It is not known if Edarbi passes into your breast milk. You and your doctor should decide if you will take Edarbi or breastfeed. You should not do both. Talk with your doctor about the best way to feed your baby if you take Edarbi.

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements.

Especially tell your doctor if you take:

• other medicines used to treat your high blood pressure or heart problem
• water pills (diuretic)

Ask your doctor if you are not sure if you are taking a medicine listed above.

Know the medicines you take. Keep a list of them and show it to your doctor or pharmacist when you get a new medicine.

How should I take Edarbi?

• Your doctor will tell you how much Edarbi to take and when to take it. Follow his/her instructions.
• Edarbi can be taken with or without food.
• If you take too much Edarbi, call your doctor or go to the nearest hospital emergency room right away.

What are the possible side effects of Edarbi?

Edarbi may cause side effects, including:

• Harm or death to your unborn fetus if taken in the second or third trimester. See "What is the most important information I should know about Edarbi?"
• Low blood pressure (hypotension) and dizziness is most likely to happen if you also:
  • take water pills (diuretics)
  • are on a low-salt diet
  • take other medicines that affect your blood pressure
  • get sick with vomiting or diarrhea
  • do not drink enough fluids

If you feel faint or dizzy, lie down and call your doctor right away.

These are not all the possible side effects with Edarbi. Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How do I store Edarbi?

• Store Edarbi at 59°F to 86°F (15°C to 30°C).
• Store Edarbi in the original container that you received from your pharmacist or doctor. Do not put Edarbi into a different container.
• Keep Edarbi in a tightly closed container, and keep Edarbi out of the light.

Keep Edarbi and all medicines out of the reach of children.

General information about Edarbi.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not give Edarbi to other people, even if they have the same symptoms you have. It may harm them.

This Patient Information leaflet summarizes the most important information about Edarbi. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about Edarbi that is written for health professionals.

For more information, go to www.Edarbi.com or call 1-866-516-4950.

What is high blood pressure (hypertension)?

Blood pressure is the force in your blood vessels when your heart beats and when your heart rests. You have high blood pressure when the force is too great.

High blood pressure makes the heart work harder to pump blood through the body and causes damage to the blood vessels. Edarbi tablets can help your blood vessels relax so your blood pressure is lower. Medicines that lower your blood pressure may lower your chance of having a stroke or heart attack.

What are the ingredients in Edarbi?

Active ingredient: azilsartan medoxomil

Inactive ingredients: mannitol, fumaric acid, sodium hydroxide, hydroxypropyl cellulose, croscarmellose sodium, microcrystalline cellulose, and magnesium stearate.

Manufactured by:
Takeda
Osaka, Japan

Manufactured for:

arbor
PHARMACEUTICALS, LLC

Atlanta, GA 30328

Revised: October 2016

Edarbi is a trademark of Takeda Pharmaceutical Company Limited registered with the U.S. Patent and Trademark Office and used under license by Arbor Pharmaceuticals, LLC.

©2016 Arbor Pharmaceuticals, LLC

EB-PI-03

Usual Adult Dose for Hypertension:

Initial dose: 80 mg orally once daily. It may be appropriate to initiate dosage at 40 mg orally once daily for patients who are treated with high doses of diuretics.

Maintenance dose: 80 mg orally once daily