Did You Know?

Every mm Hg Matters

Even modest reductions in SBP have been linked to lower risk for coronary- and stroke-related deaths^2,3,a

See Study Data

At week 6, Edarbi^® 80 mg delivered statistically superior mean ambulatory SBP reductions compared with Diovan or Benicar^7,16

Mean ambulatory SBP reduction at 6 weeks¹⁶

Study Design

^aCardiovascular risk reduction with Edarbi has not been established.

IMPORTANT SAFETY INFORMATION

INDICATIONS

EDARBI is an angiotensin II receptor blocker (ARB) indicated for the treatment of hypertension in adults, to lower blood pressure and EDARBYCLOR is an angiotensin II receptor blocker (ARB) and a thiazide-like diuretic combination product indicated for the treatment of hypertension to lower blood pressure. EDARBI may be used either alone or in combination with other antihypertensive agents. EDARBYCLOR may be used if a patient is not adequately controlled on monotherapy or as initial therapy if multiple drugs are needed to help achieve blood pressure goals. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. There are no controlled trials demonstrating risk reduction with EDARBI or EDARBYCLOR, but trials with chlorthalidone and at least one antihypertensive agent pharmacologically similar to azilsartan medoxomil have demonstrated such benefits. 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 hypertension 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). EDARBI and EDARBYCLOR may be used with other antihypertensive agents.

WARNING: FETAL TOXICITY

See full Prescribing Information for complete boxed warnings.

When pregnancy is detected, discontinue EDARBI or EDARBYCLOR as soon as possible.
Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.

WARNINGS AND PRECAUTIONS

EDARBYCLOR is contraindicated in patients with anuria.

Do not coadminister aliskiren-containing products with EDARBI or EDARBYCLOR in patients with diabetes.

Fetal Toxicity: EDARBI or EDARBYCLOR can cause fetal harm when administered to a pregnant woman. 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 neoatal 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 or EDARBYCLOR as soon as possible. Thiazides cross the placental barrier and appear in cord blood and may be associated with adverse reactions, including fetal or neonatal jaundice and thrombocytopenia.

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 or EDARBYCLOR. Such patients are probably not good candidates to start therapy with more than one drug; therefore, correct volume prior to administration of EDARBYCLOR. Correct volume or salt depletion prior to administering 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.

Impaired Renal Function: Monitor for worsening renal function in patients with renal impairment. Consider withholding or discontinuing EDARBYCLOR if progressive renal impairment becomes evident. As a consequence of inhibiting the renin-angiotensin system, changes in renal function may be anticipated in susceptible individuals treated with EDARBI or EDARBYCLOR. 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 or EDARBYCLOR. 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 azilsartan medoxomil in patients with unilateral or bilateral renal artery stenosis, but similar results are expected. In patients with renal disease, chlorthalidone may precipitate azotemia. If progressive renal impairment becomes evident, as indicated by increased blood urea nitrogen, consider withholding or discontinuing diuretic therapy.

Serum Electrolyte Imbalances: Thiazide diuretics can cause hyponatremia and hypokalemia. Drugs that inhibit the renin angiotensin system can cause hyperkalemia. Hypokalemia is a dose-dependent adverse reaction that may develop with chlorthalidone. Co-administration of digitalis may exacerbate the adverse effects of hypokalemia. Monitor serum electrolytes periodically. EDARBYCLOR attenuates chlorthalidone-associated hypokalemia. In patients with normal potassium levels at baseline, 1.7% of EDARBYCLOR-treated patients, 0.9% of azilsartan medoxomil-treated patients, and 13.4% of chlorthalidone-treated patients shifted to low potassium values (less than 3.4 mmol/L).

Hyperuricemia: Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving chlorthalidone or other thiazide diuretics.

ADVERSE REACTIONS (AEs):

The most common AE that occurred more frequently with EDARBI than placebo in adults was diarrhea (2% vs 0.5%).
AEs occurred at an incidence of ≥2% of EDARBYCLOR-treated patients and greater than azilsartan medoxomil or chlorthalidone were dizziness (8.9%) and fatigue (2.0%).

The incidence of consecutive increases of creatinine (≥50% from baseline and >ULN) was 2.0% in patients treated with the recommended doses of Edarbyclor compared with 0.4% and 0.3% with azilsartan medoxomil and chlorthalidone, respectively.

DRUG INTERACTIONS:

Monitor renal function periodically in patients receiving EDARBI or EDARBYCLOR and NSAIDs who are also elderly, volume-depleted (including those on diuretics), or who have compromised renal function, as deterioration of renal function, including possible acute renal failure, may result. These effects are usually reversible. NSAIDs may reduce the antihypertensive effect of EDARBI or EDARBYCLOR.
Dual blockade of the renin-angiotensin system (RAS) with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on EDARBI or EDARBYCLOR and other agents that affect the RAS. Do not coadminister aliskiren with EDARBI or EDARBYCLOR in patients with diabetes or renal impairment (GFR <60 mL/min).
Renal clearance of lithium is reduced by diuretics, such as chlorthalidone, increasing the risk of lithium toxicity. Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor agonists. Monitor serum lithium levels during concomitant use.

The Important Safety Information does not include all the information needed to use EDARBI and EDARBYCLOR safely and effectively.

For further information, please see complete Prescribing Information for EDARBI and EDARBYCLOR.

To report SUSPECTED ADVERSE REACTIONS, contact Azurity Pharmaceuticals, Inc. at 1-800-461-7449 or to the FDA at www.fda.gov/medwatch or call 1-800-FDA-1088.

Lowering SBP by as little as 2 mm Hg has been linked
to estimated reductions in CV mortality^2,3,a-c

Abbreviation: CHD=coronary heart disease

^aStudy Design: SBP and mortality were analyzed in 5 large population follow-up studies: Multiple Risk Factor Intervention Trial, Whitehall Study, Chicago Western Electric Study, Framingham Heart Study, and Chicago Heart Association Detection Project in Industry. For each study, the association between initial SBP and death was examined. Follow-up lasted 6 to 19 years. Multivariate coefficients for these studies were similar and averaged.²

^bPopulation estimation.

^cCV risk reduction with Edarbi^® and Edarbyclor^® has not been
established.

Study Design: Randomized, double-blind, multicenter, placebo- and active-controlled trial (N=1291) compared efficacy and safety of Edarbi^® (azilsartan medoxomil) vs placebo, Benicar (olmesartan), and Diovan (valsartan) for 6 weeks. Randomization occurred after a 3- to 4-week washout of hypertension treatment followed by a 2-week, single-blind placebo run-in period.¹⁶

Primary Endpoint: Change from baseline in 24-hour mean SBP at 6 weeks.¹⁶

Study Arms: Patients were randomly assigned placebo, 20 or 40 mg Edarbi, Diovan 160 mg, or Benicar 20 mg once daily for 2 weeks, then force titrated to AZL-M 40 or 80 mg, valsartan 320 mg, olmesartan 40 mg, or placebo for an additional 4 weeks.¹⁶

Key Inclusion Criteria: Patients were included if their clinic SBP was ≥150 mm Hg and ≤180 mm Hg and 24-hour mean SBP was ≥130 mm Hg and ≤170 mm Hg.¹⁶

Key Exclusion Criteria¹⁶:

Secondary hypertension
Significant renal disorders
Significant metabolic disorders

Significant hepatic disorders
Significant psychiatric disorders

References

1. World Health Organization. A global brief on Hypertension Silent Killer, Global Public Health Crisis. World Health Organization. 2013; 1–40. 2. Stamler R. Implications of the INTERSALT study. Hypertension. 1991;17(suppl 1):116-120. 3. Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42(6):1206-1252. 4. Fryar CD, Kit B, Carroll MD, Afful J. Hypertension prevalence, awareness, treatment, and control among adults age 18 and older: United States, August 2021–August 2023. NCHS Data Brief. Accessed January 29, 2025. 5. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018;71(19):e127-248. 6. CDC. High Blood Pressure Facts. Accessed January 28, 2025. https://www.cdc.gov/high-blood-pressure/data-research/facts-stats/index.html 7. Edarbi [package insert]. Woburn, MA: Azurity Pharmaceuticals, Inc; 2024. 8. Ojima M, Igata H, Tanaka M, et al. In vitro antagonistic properties of a new angiotensin type 1 receptor blocker, azilsartan, in receptor binding and function studies. J Pharmacol Exp Ther. 2011;336(3):801-808. 9. Miura S, Okabe A, Matsuo Y, Karnik SS, Saku K. Unique binding behavior of the recently approved angiotensin II receptor blocker azilsartan compared with that of candesartan. Hypertens Res. 2013;36(2):134-139. 10. Benicar [package insert]. South Plainfield, NJ: Cosette Pharmaceuticals, Inc; 2022. 11. Diovan [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2021. 12. Avapro [package insert]. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2021. 13. Atacand [package insert]. Södertälje, Sweden: AstraZeneca AB; 2020. 14. Micardis [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2022. 15. Cozaar [package insert]. Jersey City, NJ: Organon LLC, a subsidiary of Organon & Co.; 2021. 16. White WB, Weber MA, Sica D, et al. Effects of the angiotensin receptor blocker azilsartan medoxomil versus olmesartan and valsartan on ambulatory and clinic blood pressure in patients with stages 1 and 2 hypertension. Hypertension. 2011;57(3):413-420. 17. Edarbyclor [package insert]. Woburn, MA: Azurity Pharmaceuticals, Inc; 2022. 18. Guerrero-Garcia C, Rubio-Guerra AF. Combination therapy in the treatment of hypertension. Drugs Context. 2018;7:212531. 19. Cushman WC, Bakris GL, White WB, et al. Azilsartan medoxomil plus chlorthalidone reduces blood pressure more effectively than olmesartan plus hydrochlorothiazide in stage 2 systolic hypertension. Hypertension. 2012;60(2):310-318. 20. Ferdinand KC, Bakris GL, Cushman WC, et al. Comparison of effectiveness of azilsartan medoxomil and olmesartan in Blacks versus whites with systemic hypertension. Am J Cardiol. 2018;122(9):1496-1505. 21. Rethy L, Shah NS, Paparello JJ, Lloyd-Jones DM, Khan SS. Trends in Hypertension-Related Cardiovascular Mortality in the United States, 2000 to 2018. Hypertension. 2020;76(3):e23-e25. 22. Du LP, Cheng ZW, Zhang YX, Li Y, Mei D. The impact of fixed-dose combination versus free-equivalent combination therapies on adherence for hypertension: a meta-analysis. J Clin Hypertens (Greenwich). 2018;20(5):902-907.