Adult Dosing

Hypertension

• Start 40/12.5 mg PO Daily initially; may increase to 40 mg/25 mg after 2-4 weeks as needed to achieve blood pressure goals
• Max: 40/25 mg/day

Note:

• May be administered with other anti-hypertensive agents
• May be administered with or without food
• Replace volume in volume-depleted patients prior to use

Pediatric Dosing

• Safety and effectiveness in pediatric patients <18 years of age have not been established

• Hypertension
• Indicated for treatment of hypertension in patients not adequately controlled with monotherapy, or as initial therapy in patients likely to need multiple drugs to help achieve blood pressure goals

• Hypersensitivity to any of the ingredients of the product
• Anuria
• Do not co-administer along with aliskiren in patients with diabetes

• When pregnancy is detected, discontinue therapy as soon as possible; drugs affecting renin-angiotensin system may result in fetal injury and/or death

Renal Dose Adjustment (Based on CrCl)

• Mild-moderate impairment (eGFR 30 mL/min/1.73 sq.meter or greater): No dose adjustments
• Severe impairment (eGFR <30 mL/min/1.73 sq.meter): Dose adjustments not defined
• Chlorthalidone may precipitate azotemia
• Progressive renal impairment: treatment should be withheld

Hepatic Dose Adjustment

• Mild-moderate impairment: No dose adjustments
• Severe impairment: Dose adjustments not defined
• Chlorthalidone may cause mild alterations of fluid and electrolyte balance that may precipitate hepatic coma in patients with impaired hepatic function or progressive liver disease

• When pregnancy is detected, discontinue therapy as soon as possible; drugs affecting renin-angiotensin system may result in fetal injury and/or death [US blackbox warning]
• Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy may results in potential neonatal adverse effects which may include skull hypoplasia, anuria, hypotension, renal failure, and death
• Chlorthalidone crosses the placental barrier and appear in cord blood. Adverse reactions include fetal or neonatal jaundice and thrombocytopenia
• Symptomatic hypotension may occur after initiation of therapy 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)
• Closely monitor patients with renal impairment for worsening renal function. Consider withholding or discontinuing therapy
• In patients whose renal function depends 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
• Use of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen have been reported
• In patients with renal disease, chlorthalidone may precipitate azotemia
• Hypokalemia is a dose-dependent adverse reaction that may develop with chlorthalidone
• In patients receiving chlorthalidone or other thiazide diuretics, hyperuricemia may occur or frank gout may be precipitated

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. Discontinue therapy as soon as pregnancy is detected

Breastfeeding: It is not known if this drugs is 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.

• CNS:Dizziness, fatigue, syncope
• CV: Hypotension
• LAB TESTS: Serum creatinine increased

Azilsartan

• Angiotensin II receptor blocker (ARB); blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, including vascular smooth muscle and the adrenal gland
• Absolute bioavailability: 60%
• Metabolized in liver; CYP450: 2C9 substrate
• Excreted in feces (55%) and urine 42% (15% unchanged)
• Half-life: 12 hrs

Chlorthalidone

• Thiazide diuretic; roduces diuresis with increased excretion of sodium and chloride at the cortical diluting segment of the ascending limb of Henle’s loop of the nephron
• Rapidly absorbed after administration
• Not metabolized
• Excreted unchanged by the kidneys (50-75%)
• Half-life: 40-60 hrs

US Trade Name(s)

• Edarbyclor

US Availability

Edarbyclor (azilsartan/chlorthalidone)

• TABS: 40/12.5 mg
• TABS: 40/25 mg

Canadian Trade Name(s)

• N/A

Canadian Availability

• N/A

UK Trade Name(s)

• N/A

UK Availability

• N/A

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

Cardiovascular

Antihypertensive Combinations