Drug: Edarbyclor

Edarbyclor is a combination of azilsartan medoxomil (ARB; as its potassium salt) and chlorthalidone (thiazide-like diuretic). Azilsartan medoxomil, a prodrug, is hydrolyzed to azilsartan in the gastrointestinal tract during absorption. Azilsartan is a selective AT1 subtype angiotensin II receptor antagonist. Chlorthalidone is a monosulfamyl thiazide-like diuretic that differs chemically from thiazide diuretics by the lack of a benzothiadiazine structure. The potassium salt of azilsartan medoxomil, azilsartan kamedoxomil, is chemically described as (5Methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4yl]methyl}-1H-benzimidazole-7-carboxylate monopotassium salt. Its empirical formula is C30H23KN4O8. Chlorthalidone is chemically described as 2-chloro-5(1-hydroxy-3-oxo-1- isoindolinyl) benzenesulfonamide. Its empirical formula is C14H11ClN2O4S. The structural formula for azilsartan medoxomil is The Structural formula for chlorthalidone 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. Chlorthalidone is a white to yellowish white powder with a molecular weight of 338.76. Chlorthalidone is practically insoluble in water, in ether, and in chloroform; soluble in methanol; slightly soluble in ethanol. Edarbyclor is available for oral use as tablets. The tablets have a characteristic odor. Each Edarbyclor tablet contains 42.68 mg of azilsartan kamedoxomil, which is equivalent to containing azilsartan medoxomil 40 mg plus 12.5 or 25 mg of chlorthalidone. Each tablet of Edarbyclor also contains the following inactive ingredients: mannitol, microcrystalline cellulose, fumaric acid, sodium hydroxide, hydroxypropyl cellulose, crospovidone, magnesium stearate, hypromellose 2910, talc, titanium dioxide, ferric oxide red, polyethylene glycol 8000, and printing ink gray F1.

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The following potential adverse reactions with Edarbyclor, azilsartan medoxomil, or chlorthalidone and similar agents are included in more detail in the WARNINGS AND PRECAUTIONS section of the label:
  • Fetal toxicity [see WARNINGS AND PRECAUTIONS]
  • Hypotension in Volume- or Salt-Depleted Patients [see WARNINGS AND PRECAUTIONS]
  • Impaired Renal Function [see WARNINGS AND PRECAUTIONS]
  • Hypokalemia [see WARNINGS AND PRECAUTIONS]
  • Hyperuricemia [see WARNINGS AND PRECAUTIONS]
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. Edarbyclor has been evaluated for safety in more than 3900 patients with hypertension; more than 700 patients were treated for at least 6 months and more than 280 for at least 1 year. Adverse reactions have generally been mild and transient in nature. Common adverse reactions that occurred in the 8-week factorial design trial in at least 2% of Edarbyclor-treated patients and greater than azilsartan medoxomil or chlorthalidone are presented in Table 1. Table 1: Adverse Reactions Occurring at an Incidence of ≥ 2% of Edarbyclor-treated Patients and > Azilsartan medoxomil or Chlorthalidone
Preferred Term Azilsartan medoxomil 20, 40, 80 mg
(N=470) Chlorthalidone 12.5, 25 mg
(N=316) Edarbyclor 40 / 12.5, 40 / 25 mg
(N=302) Dizziness 1.7% 1.9% 8.9% Fatigue 0.6% 1.3% 2.0% Hypotension and syncope were reported in 1.7% and 0.3%, respectively, of patients treated with Edarbyclor. Study discontinuation because of adverse reactions occurred in 8.3% of patients treated with the recommended doses of Edarbyclor compared with 3.2% of patients treated with azilsartan medoxomil and 3.2% of patients treated with chlorthalidone. The most common reasons for discontinuation of therapy with Edarbyclor were serum creatinine increased (3.6%) and dizziness (2.3%). The adverse reaction profile obtained from 52 weeks of open-label combination therapy with azilsartan medoxomil plus chlorthalidone or Edarbyclor was similar to that observed during the double-blind, active controlled trials. In 3 double-blind, active controlled, titration studies, in which Edarbyclor was titrated to higher doses in a step-wise manner, adverse reactions and discontinuations for adverse events were less frequent than in the fixed-dose factorial trial. Azilsartan Medoxomil A total of 4814 patients were evaluated for safety when treated with azilsartan medoxomil 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. Generally, adverse reactions were mild, not dose related and similar regardless of age, gender and race. 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 azilsartan medoxomil in controlled trials are listed below: Gastrointestinal Disorders: diarrhea, nausea General Disorders and Administration Site Conditions: asthenia, fatigue Musculoskeletal and Connective Tissue Disorders: muscle spasm Nervous System Disorders: dizziness, dizziness postural Respiratory, Thoracic and Mediastinal Disorders: cough Chlorthalidone The following adverse reactions have been observed in clinical trials of chlorthalidone: rash, headache, dizziness, GI upset, and elevations of uric acid and cholesterol. Clinical Laboratory Findings with Edarbyclor In the factorial design trial, clinically relevant changes in standard laboratory parameters were uncommon with administration of the recommended doses of Edarbyclor. Renal Parameters Increased blood creatinine is a known pharmacologic effect of renin-angiotensin aldosterone system (RAAS) blockers, such as ARBs and ACE inhibitors, and is related to the magnitude of blood pressure reduction. 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. Elevations of creatinine were typically transient, or non-progressive and reversible, and associated with large blood pressure reductions. Mean increases in blood urea nitrogen (BUN) were observed with Edarbyclor (5.3 mg/dL) compared with azilsartan medoxomil (1.5 mg/dL) and with chlorthalidone (2.5 mg/dL). Postmarketing Experience The following adverse reactions have been identified during the postmarketing use of EDARBYCLOR. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
  • Nausea
  • Rash
  • Pruritus
  • Angioedema
Read the Edarbyclor (azilsartan medoxomil and chlorthalidone tablets) Side Effects Center for a complete guide to possible side effectsLearn More »

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Dosing Information The recommended starting dose of Edarbyclor is 40/12.5 mg taken orally once daily. Most of the antihypertensive effect is apparent within 1 to 2 weeks. The dosage may be increased to 40/25 mg after 2 to 4 weeks as needed to achieve blood pressure goals. Edarbyclor doses above 40/25 mg are probably not useful. Edarbyclor may be used to provide additional blood pressure lowering for patients not adequately controlled on ARB or diuretic monotherapy treatment. Patients not controlled with azilsartan medoxomil 80 mg may have an additional systolic / diastolic clinic blood pressure reduction of 13/6 mm Hg when switched to Edarbyclor 40/12.5 mg. Patients not controlled with chlorthalidone 25 mg may have an additional clinic blood pressure reduction of 10/7 mm Hg when switched to Edarbyclor 40/12.5 mg. Edarbyclor may be used as initial therapy if a patient is likely to need multiple drugs to achieve blood pressure goals. Patients titrated to the individual components (azilsartan medoxomil and chlorthalidone) may instead receive the corresponding dose of Edarbyclor. Edarbyclor may be taken with or without food [see CLINICAL PHARMACOLOGY]. Edarbyclor may be administered with other antihypertensive agents as needed. Prior To Dosing Correct any volume depletion prior to administration of Edarbyclor, particularly in patients with impaired renal function or those treated with high doses of diuretics [see WARNINGS AND PRECAUTIONS]. Patients who experience dose-limiting adverse reactions on chlorthalidone may be switched to Edarbyclor, initially with a lower dose of chlorthalidone [see WARNINGS AND PRECAUTIONS]. Handling Instructions As Edarbyclor is moisture sensitive, dispense and store Edarbyclor in its original container to protect Edarbyclor from light and moisture.

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Edarbyclor The pharmacokinetics of azilsartan medoxomil and chlorthalidone are not altered when the drugs are co-administered. No drug interaction studies have been conducted with other drugs and Edarbyclor, although studies have been conducted with azilsartan medoxomil and chlorthalidone. Azilsartan Medoxomil 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, azilsartan medoxomil 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 Edarbyclor and NSAID therapy. The antihypertensive effect of Edarbyclor may be attenuated by NSAIDs, including selective COX-2 inhibitors. Dual Blockade of the Renin-Angiotensin System (RAS) Dual blockade of the 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. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on Edarbyclor and other agents that affect the RAS. Do not coadminister aliskiren with Edarbyclor in patients with diabetes. Avoid use of aliskiren with Edarbyclor in patients with renal impairment (GFR < 60 mL/min). Chlorthalidone Lithium renal clearance is reduced by diuretics, such as chlorthalidone, increasing the risk of lithium toxicity. Consider monitoring lithium levels when using Edarbyclor. Lithium 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. Last reviewed on RxList: 5/6/2015
This monograph has been modified to include the generic and brand name in many instances.

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Edarbyclor contains an angiotensin II receptor blocker (ARB) and a thiazide-like diuretic and is indicated for the treatment of hypertension, to lower blood pressure. Edarbyclor may be used in patients whose blood pressure is not adequately controlled on monotherapy. Edarbyclor may be used as initial therapy if a patient is likely to need multiple drugs to achieve blood pressure goals. 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 thiazide-like diuretics such as chlorthalidone and ARBs such as azilsartan medoxomil. There are no controlled trials demonstrating risk reduction with Edarbyclor. 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 of high blood pressure, 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; however, the blood pressure effect of Edarbyclor in blacks is similar to that in non-blacks. 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. The choice of Edarbyclor as initial therapy for hypertension should be based on an assessment of potential benefits and risks including whether the patient is likely to tolerate the starting dose of Edarbyclor. Patients with moderate-to-severe hypertension are at a relatively high risk of cardiovascular events (e.g., stroke, heart attack, and heart failure), kidney failure, and vision problems, so prompt treatment is clinically relevant. Consider the patient's baseline blood pressure, target goal and the incremental likelihood of achieving the goal with a combination product, such as Edarbyclor, versus a monotherapy product when deciding upon initial therapy. Individual blood pressure goals may vary based on the patient's risk. Data from an 8-week, active-controlled, factorial trial provide estimates of the probability of reaching a target blood pressure with Edarbyclor compared with azilsartan medoxomil or chlorthalidone monotherapy [see Clinical Studies]. Figures 1.a-1.d provide estimates of the likelihood of achieving target clinic systolic and diastolic blood pressure control with Edarbyclor 40/25 mg tablets after 8 weeks, based on baseline systolic or diastolic blood pressure. The curve for each treatment group was estimated by logistic regression modeling and is more variable at the tails. Figure 1a: Probability of Achieving Systolic Blood Pressure < 140 mmHg at Week 8
Figure 1b: Probability of Achieving Systolic Blood Pressure < 130 mmHg at Week 8
Figure 1c: Probability of Achieving Diastolic Blood Pressure < 90 mmHg at Week 8
Figure 1d: Probability of Achieving Diastolic Blood Pressure < 80 mmHg at Week 8
For example, a patient with a baseline blood pressure of 170/105 mm Hg has approximately a 48% likelihood of achieving a goal of < 140 mm Hg (systolic) and 48% likelihood of achieving < 90 mm Hg (diastolic) on azilsartan medoxomil 80 mg. The likelihood of achieving these same goals on chlorthalidone 25 mg is approximately 51% (systolic) and 40% (diastolic). These likelihoods rise to 85% (systolic) and 85% (diastolic) with Edarbyclor 40/25 mg.

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Edarbyclor is contraindicated in patients with anuria [see WARNINGS AND PRECAUTIONS]. Do not coadminister aliskiren with Edarbyclor in patients with diabetes [see DRUG INTERACTIONS]. Last reviewed on RxList: 5/6/2015
This monograph has been modified to include the generic and brand name in many instances.

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Limited data are available related to overdosage in humans. Azilsartan medoxomil Limited data are available related to overdosage in humans. During controlled clinical trials in healthy subjects, once daily doses up to 320 mg of azilsartan medoxomil 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. Chlorthalidone Symptoms of acute overdosage include nausea, weakness, dizziness, and disturbances of electrolyte balance. The oral LD50 of the drug in the mouse and the rat is more than 25,000 mg/kg body weight. The minimum lethal dose (MLD) in humans has not been established. There is no specific antidote, but gastric lavage is recommended, followed by supportive treatment. Where necessary, this may include intravenous dextrose-saline with potassium, administered with caution.

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Dosage Forms And Strengths Edarbyclor is supplied in the following dosage strengths:
  • 40/12.5 mg: pale red, round, biconvex, film-coated tablets, approximately 9.7 mm in diameter, with “A/C” and “40/12.5” imprinted on one side. Each tablet contains 40 mg of azilsartan medoxomil and 12.5 mg of chlorthalidone.
  • 40/25 mg: light red, round, biconvex, film-coated tablets, approximately 9.7 mm in diameter, with “A/C” and “40/25” imprinted on one side. Each tablet contains 40 mg of azilsartan medoxomil and 25 mg of chlorthalidone.
Storage And Handling Edarbyclor is supplied as fixed dose combination tablets that are round, biconvex, film-coated, and 9.7 mm in diameter. Strength Color Imprinting NDC Number 60631-xxx-xx Bottle of 30 40 / 12.5 mg Pale red A/C 40/12.5 412-30 40 / 25 mg Light red A/C 40/25 425-30 Store at 25°C (77°F), excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature]. Keep container tightly closed. Protect from moisture and light. Do not repackage; dispense and store in original container. Osaka, Japan Manufactured for: Atlanta, GA 30328. Revised: April 2015 Last reviewed on RxList: 5/6/2015
This monograph has been modified to include the generic and brand name in many instances.

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Fetal Toxicity Azilsartan Medoxomil 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 Edarbyclor as soon as possible [see Use in Specific Populations]. Chlorthalidone Thiazides cross the placental barrier and appear in cord blood. Adverse reactions include fetal or neonatal jaundice and thrombocytopenia. Hypotension In Volume- Or Salt-Depleted Patients In patients with an activated renin-angiotensin system, such as volume- or salt-depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of treatment with Edarbyclor. Such patients are probably not good candidates to start therapy with more than one drug; therefore, correct volume prior to administration of Edarbyclor. 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 Edarbyclor Monitor for worsening renal function in patients with renal impairment. Consider withholding or discontinuing Edarbyclor if progressive renal impairment becomes evident. Azilsartan Medoxomil As a consequence of inhibiting the renin-angiotensin system, changes in renal function may be anticipated in susceptible individuals treated with 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 Edarbyclor [see DRUG INTERACTIONS, Use In Specific Populations and CLINICAL PHARMACOLOGY]. 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. Chlorthalidone 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 Chlorthalidone Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving chlorthalidone or other thiazide diuretics. Patient Counseling Information See FDA-approved patient labeling (PATIENT INFORMATION). Tell patients that if they miss a dose, they should take it later in the same day, but not to double the dose on the following day. Pregnancy Tell female patients of childbearing potential about the consequences of exposure to Edarbyclor during pregnancy. Discuss treatment options with women planning to become pregnant. Tell patients to report pregnancies to their physicians as soon as possible. Symptomatic Hypotension Advise patients to report light-headedness. Advise patients, if syncope occurs, to have someone call the doctor or seek medical attention, and to discontinue Edarbyclor. Inform patients that dehydration from excessive perspiration, vomiting, or diarrhea may lead to an excessive fall in blood pressure. Inform patients to consult with their healthcare provider if these symptoms occur. Renal Impairment Inform patients with renal impairment that they should receive periodic blood tests to monitor their renal function while taking Edarbyclor. Gout Have patients report gout symptoms. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility No carcinogenicity, mutagenicity, or fertility studies have been conducted with the combination of azilsartan medoxomil and chlorthalidone. However, these studies have been conducted for azilsartan medoxomil alone. Azilsartan Medoxomil Carcinogenesis Azilsartan medoxomil was not carcinogenic when assessed in 26-week transgenic (Tg.rasH2) mouse and 2-year rat studies. The highest doses tested (450 mg azilsartan medoxomil/kg/day in the mouse and 600 mg azilsartan medoxomil/kg/day in the rat) produced exposures to azilsartan that are 12 (mice) and 27 (rats) times the average exposure to azilsartan in humans given the maximum recommended human dose (MRHD, 80 mg azilsartan medoxomil/day). M-II was not carcinogenic when assessed in 26-week Tg.rasH2 mouse and 2-year rat studies. The highest doses tested (approximately 8000 mg M-II/kg/day (males) and 11,000 mg M-II/kg/day (females) in the mouse and 1000 mg M-II/kg/day (males) and up to 3000 mg M-II/kg/day (females) in the rat) produced exposures that are, on average, about 30 (mice) and 7 (rats) times the average exposure to M-II in humans at the MRHD. Mutagenesis Azilsartan medoxomil, azilsartan, and M-II were positive for structural aberrations in the Chinese Hamster Lung Cytogenic Assay. In this assay, structural chromosomal aberrations were observed with the prodrug, azilsartan medoxomil, without metabolic activation. The active moiety, azilsartan, was also positive in this assay both with and without metabolic activation. The major human metabolite, M-II was also positive in this assay during a 24-hr assay without metabolic activation. Azilsartan medoxomil, azilsartan, and M-II were devoid of genotoxic potential in the Ames reverse mutation assay with Salmonella typhimurium and Escherichia coli, the in vitro Chinese Hamster Ovary Cell forward mutation assay, the in vitro mouse lymphoma (tk) gene mutation test, the ex vivo unscheduled DNA synthesis test, and the in vivo mouse and/or rat bone marrow micronucleus assay. Impairment of Fertility There was no effect of azilsartan medoxomil on the fertility of male or female rats at oral doses of up to 1000 mg azilsartan medoxomil/kg/day [6000 mg/m² (approximately 122 times the MRHD of 80 mg azilsartan medoxomil/60 kg on a mg/m² basis)]. Fertility of rats also was unaffected at doses of up to 3000 mg M-II/kg/day. Use In Specific Populations 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 Edarbyclor 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 reninangiotensin 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 Edarbyclor, 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 Edarbyclor for hypotension, oliguria, and hyperkalemia [see Use in Specific Populations]. 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 and thiazide-like diuretics like chlorthalidone are excreted in human milk. 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 Safety and effectiveness of Edarbyclor in pediatric patients under 18 years of age have not been established. Neonates with a history of in utero exposure to Edarbyclor: If oliguria or hypotension occurs, support blood pressure and renal function. Exchange transfusions or dialysis may be required. Geriatric Use Edarbyclor No dose adjustment with Edarbyclor is necessary in elderly patients. Of the total patients in clinical studies with Edarbyclor, 24% were elderly (65 years of age or older); 5.7% were 75 years and older. No overall 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]. Renal Impairment Edarbyclor Safety and effectiveness of Edarbyclor in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m²) have not been established. No dose adjustment is required in patients with mild (eGFR 60-90 mL/min/1.73 m²) or moderate (eGFR 30-60 mL/min/1.73 m²) renal impairment. Chlorthalidone Chlorthalidone may precipitate azotemia. Hepatic Impairment Azilsartan Medoxomil No dose adjustment is necessary for subjects with mild or moderate hepatic impairment. Azilsartan medoxomil has not been studied in patients with severe hepatic impairment [see CLINICAL PHARMACOLOGY]. Chlorthalidone Minor alterations of fluid and electrolyte balance may precipitate hepatic coma in patients with impaired hepatic function or progressive liver disease. Last reviewed on RxList: 5/6/2015
This monograph has been modified to include the generic and brand name in many instances.

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