Edarbi Information
Edarbi ()
Edarbi () Dosage And Administration
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 .
Edarbi () Dosage Forms And Strengths
Edarbi () is supplied as white to nearly white round tablets in the following dosage strengths:
Edarbi () Contraindications
Edarbi () Warnings And Precautions
Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity and death when administered to pregnant women during the second and third trimester. When pregnancy is detected, Edarbi () should be discontinued as soon as possible.
The use of drugs that act directly on the renin-angiotensin system during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function; oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development. Prematurity, intrauterine growth retardation, and patent ductus arteriosus have also been reported, although it is not clear whether these occurrences were due to exposure to the drug.
These adverse effects do not appear to have resulted from intrauterine drug exposure that has been limited to the first trimester. Mothers whose embryos and fetuses are exposed to an angiotensin II receptor antagonist only during the first trimester should be so informed. Nonetheless, when patients become pregnant, physicians should have the patient discontinue the use of Edarbi () as soon as possible.
Rarely (probably less often than once in every thousand pregnancies), no alternative to a drug acting on the renin-angiotensin system is available. In these rare cases, the mother should be apprised of the potential hazards to the fetus and serial ultrasound examinations should be performed to assess the intra-amniotic environment.
If oligohydramnios is observed, Edarbi () should be discontinued unless it is considered life-saving for the mother. Contraction stress testing, a nonstress test or biophysical profiling may be appropriate, depending upon the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.
Infants with histories of exposure to an angiotensin II receptor antagonist should be closely observed for hypotension, oliguria, and hyperkalemia. If oliguria occurs, attention should be directed toward support of blood pressure and renal perfusion. Exchange transfusion or dialysis may be required as a means of reversing hypotension and/or substituting for 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 ()
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.
Edarbi () Adverse Reactions
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 evaluated 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 6 months; of these, 588 were treated for at least 1 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, adverse reactions were mild, not dose related and similar regardless of age, gender and race.
In placebo controlled monotherapy trials, diarrhea was reported up to 2% in patients treated with Edarbi () 80 mg daily compared with 0.5% of patients on placebo.
Other adverse reactions with a plausible relationship to treatment that have been reported with an incidence of ≥0.3% and greater than placebo in more than 3300 patients treated with Edarbi () in controlled trials are listed below:
Gastrointestinal Disorders:
General Disorders and Administration Site Conditions:
Musculoskeletal and Connective Tissue Disorders:
Nervous System Disorders:
Respiratory, Thoracic and Mediastinal Disorders:
In controlled clinical trials, clinically relevant changes in standard laboratory parameters were uncommon with administration of Edarbi () .
Serum creatinine
In addition, patients taking Edarbi () who had moderate to severe renal impairment at baseline or who were >75 years of age were more likely to report serum creatinine increases.
Hemoglobin/Hematocrit
Edarbi () Drug Interactions
No clinically significant drug interactions have been observed in studies of azilsartan medoxomil or azilsartan given with amlodipine, antacids, chlorthalidone, digoxin, fluconazole, glyburide, ketoconazole, metformin, pioglitazone, and warfarin. Therefore, Edarbi () may be used concomitantly with these medications
Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors
(COX-2 Inhibitors)
In patients who are elderly, volume-depleted (including those on diuretic therapy), or who have compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including azilsartan, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving azilsartan and NSAID therapy.
The antihypertensive effect of angiotensin II receptor antagonists, including azilsartan, may be attenuated by NSAIDs, including selective COX-2 inhibitors.
Edarbi () Overdosage
Limited data are available related to overdosage in humans. During controlled clinical trials in healthy subjects, once daily doses up to 320 mg of Edarbi () were administered for 7 days and were well tolerated. In the event of an overdose, supportive therapy should be instituted as dictated by the patient's clinical status. Azilsartan is not dialyzable .
Edarbi () Description
Edarbi () (azilsartan medoxomil), a prodrug, is hydrolyzed to azilsartan in the gastrointestinal tract during absorption. Azilsartan is a selective ATsubtype angiotensin II receptor antagonist.
The drug substance used in the drug product formulation is the potassium salt of azilsartan medoxomil, also known by the US accepted name of azilsartan kamedoxomil and is chemically described as (5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1-benzimidazole-7-carboxylate monopotassium salt.
Its empirical formula is CHKNOand its structural formula is:
Azilsartan kamedoxomil is a white to nearly white powder with a molecular weight of 606.62. It is practically insoluble in water and freely soluble in methanol.
Edarbi () is available for oral use as tablets. The tablets have a characteristic odor. Each Edarbi () tablet contains 42.68 or 85.36 mg of azilsartan kamedoxomil, which is equivalent to containing 40 mg or 80 mg respectively, of azilsartan medoxomil and the following inactive ingredients: mannitol, fumaric acid, sodium hydroxide, hydroxypropyl cellulose, croscarmellose sodium, microcrystalline cellulose, and magnesium stearate.
Edarbi () Clinical Pharmacology
Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzymes (ACE, kinase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Azilsartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is, therefore, independent of the pathway for angiotensin II synthesis.
An ATreceptor is also found in many tissues, but this receptor is not known to be associated with cardiovascular homeostasis. Azilsartan has more than a 10,000-fold greater affinity for the ATreceptor than for the ATreceptor.
Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is widely used in the treatment of hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction catalyzed by ACE. Because azilsartan does not inhibit ACE (kinase II), it should not affect bradykinin levels. Whether this difference has clinical relevance is not yet known. Azilsartan does not bind to or block other receptors or ion channels known to be important in cardiovascular regulation.
Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the effect of azilsartan on blood pressure.
Edarbi () Clinical Studies
The antihypertensive effects of Edarbi () have been demonstrated in a total of 7 double-blind, randomized studies, which included 5 placebo-controlled and 4 active comparator-controlled studies (not mutually exclusive). The studies ranged from 6 weeks to 6 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 2 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.
Edarbi () How Supplied/storage And Handling
Edarbi () tablets are unscored and white to nearly white, debossed with "ASL" on one side and "40" or "80" on the other.
Edarbi () Patient Counseling Information
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