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Edarbi (azilsartan medoxomil) tablets
2015-06-27 14:10:39 来源: 作者: 【 】 浏览:331次 评论:0
  • HIGHLIGHTS OF PRESCRIBING INFORMATION
    These HIGHLIGHTS do not include all the information needed to use EDARBI safely and effectively. See full prescribing information for EDARBI.

    Edarbi (azilsartan medoxomil) tablets
    Initial U.S. Approval: 2011
    WARNING: FETAL TOXICITY
    See full prescribing information for complete boxed warning.
    When pregnancy is detected, discontinue Edarbi as soon as possible. (5.1)
    Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. (5.1)

    RECENT MAJOR CHANGES

    Boxed Warning

    11/2011

    Contraindications (4)

    10/2012

    Warnings and Precautions

     

      Fetal Toxicity (5.1)

    11/2011

     INDICATIONS AND USAGE

    Edarbi is an angiotensin II receptor blocker 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. Edarbi may be used either alone or in combination with other antihypertensive agents. (1)
    DOSAGE AND ADMINISTRATION

    The recommended dose in adults is 80 mg taken once daily. Consider a starting dose of 40 mg for patients who are treated with high doses of diuretics. (2.1)

    Edarbi may be administered with or without food. (2.1)

    Edarbi may be administered with other antihypertensive agents. (2.1)

    DOSAGE FORMS AND STRENGTHS

    Tablets: 40 mg and 80 mg. (3)
    CONTRAINDICATIONS

    Do not coadminister aliskiren with Edarbi in patients with diabetes. (4)
    WARNINGS AND PRECAUTIONS

    Correct volume or salt depletion prior to administration of Edarbi. ( 5.2)
    Monitor for worsening renal function in patients with renal impairment. ( 5.3)
    ADVERSE REACTIONS

    The most common adverse reaction in adults was diarrhea (2%). (6.1)

    To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-877-825-3327 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    DRUG INTERACTIONS

    Dual inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension, and hyperkalemia. (7)
    USE IN SPECIFIC POPULATIONS

    Nursing Mothers: Discontinue nursing or drug. ( 8.3)
    Geriatric Patients: Abnormally high serum creatinine values were more likely to be reported for patients age 75 or older. No overall difference in efficacy versus younger patients, but greater sensitivity of some older individuals cannot be ruled out. ( 8.5)
    In patients with an activated renin-angiotensin system, as by volume- or salt-depletion, renin-angiotensin-aldosterone system (RAAS) blockers such as azilsartan medoxomil can cause excessive hypotension. In susceptible patients, e.g., with renal artery stenosis, RAAS blockers can cause renal failure ( 5.2, 5.3).
    Pediatrics: Safety and efficacy in children have not been established.
     
    See 17 for PATIENT COUNSELING INFORMATION.

    Revised: 10/2012

  • FULL PRESCRIBING INFORMATION: CONTENTS*
  • 1 INDICATIONS AND USAGE

    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, eva luation, 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.

  • 2 DOSAGE AND ADMINISTRATION

     

    2.1 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)].

    2.2 Handling Instructions

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

    2.3 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)].

  • 3 DOSAGE FORMS AND STRENGTHS

    Edarbi is supplied as white to nearly white round tablets in the following dosage strengths:

    40-mg tablets - debossed "ASL" on one side and "40" on the other
    80-mg tablets - debossed "ASL" on one side and "80" on the other
  • 4 CONTRAINDICATIONS

    Do not coadminister aliskiren with Edarbi in patients with diabetes [see Drug Interactions (7)].

  • 5 WARNINGS AND PRECAUTIONS

     

    5.1 Fetal Toxicity

    Use of drugs that act on 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 [see Use in Specific Populations (8.1)].

    5.2 Hypotension in Volume- or Salt-Depleted Patients

    In patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of treatment with Edarbi. Correct volume or salt depletion prior to administration of Edarbi, or start treatment at 40 mg. If hypotension does occur, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.

    5.3 Impaired Renal Function

    As a consequence of inhibiting the renin-angiotensin system, changes in renal function may be anticipated in susceptible individuals treated with Edarbi. In patients whose renal function may depend on the activity of the renin-angiotensin system (e.g., patients with severe congestive heart failure, renal artery stenosis, or volume depletion), treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers has been associated with oliguria or progressive azotemia and rarely with acute renal failure and death. Similar results may be anticipated in patients treated with Edarbi [see Drug Interactions (7), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].

    In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen have been reported. There has been no long-term use of Edarbi in patients with unilateral or bilateral renal artery stenosis, but similar results may be expected.

  • 6 ADVERSE REACTIONS

     

    6.1 Clinical Trials Experience

    Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

    A total of 4814 patients were eva luated for safety when treated with Edarbi at doses of 20, 40, or 80 mg in clinical trials. This includes 1704 patients treated for at least six months; of these, 588 were treated for at least one year.

    Treatment with Edarbi was well-tolerated with an overall incidence of adverse reactions similar to placebo. The rate of withdrawals due to adverse events in placebo-controlled monotherapy and combination therapy trials was 2.4% (19/801) for placebo, 2.2% (24/1072) for Edarbi 40 mg, and 2.7% (29/1074) for Edarbi 80 mg. The most common adverse event leading to discontinuation, hypotension/orthostatic hypotension, was reported by 0.4% (8/2146) patients randomized to Edarbi 40 mg or 80 mg compared to 0% (0/801) patients randomized to placebo. Generally, a

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