Azilsartan-chlorthalidone

Azilsartan is an angiotensin II receptor antagonist. Azilsartan keeps blood vessels from narrowing, which lowers blood pressure and improves blood flow.

Chlorthalidone is a thiazide diuretic (water pill) that helps prevent your body from absorbing too much salt, which can cause fluid retention.

Azilsartan and chlorthalidone is a combination medicine used to treat high blood pressure (hypertension). Lowering blood pressure may lower your risk of a stroke or heart attack.

Azilsartan and chlorthalidone may also be used for purposes not listed in this medication guide.

You should not use this medicine if you are unable to urinate.

Do not use if you are pregnant. Stop using this medicine and tell your doctor right away if you become pregnant. Azilsartan and chlorthalidone can cause injury or death to an unborn baby.

If you have diabetes, do not use azilsartan and chlorthalidone together with any medication that contains aliskiren (Amturnide, Tekturna, Tekamlo, Valturna).

You should not use this medicine if you are allergic to azilsartan or chlorthalidone, or if you are unable to urinate.

If you have diabetes, do not use azilsartan and chlorthalidone together with any medication that contains aliskiren (Amturnide, Tekturna, Tekamlo, Valturna).

You may also need to avoid taking azilsartan and chlorthalidone with aliskiren if you have kidney disease.

To make sure this medicine is safe for you, tell your doctor if you have:

• liver or kidney disease;
• gout;
• an electrolyte imbalance (such as low levels of potassium in your blood);
• a history of heart disease or stroke; or
• if you are dehydrated.

FDA pregnancy category D. Do not use if you are pregnant. Stop using and tell your doctor right away if you become pregnant. Azilsartan and chlorthalidone can cause injury or death to the unborn baby if you take the medicine during your second or third trimester. Use effective birth control.

It is not known whether azilsartan and chlorthalidone passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using this medicine.

Azilsartan and chlorthalidone is not approved for use by anyone younger than 18 years old.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• feeling like you might pass out;
• urinating less than usual or not at all;
• drowsiness, confusion, mood changes, increased thirst, loss of appetite;
• swelling, weight gain, feeling short of breath; or
• signs of electrolyte imbalance--dry mouth, extreme thirst, weakness, drowsiness, restless feeling, confusion, increased or decreased urination, nausea and vomiting, constipation, muscle pain or weakness, fast heart rate, or seizure (convulsions).

Common side effects may include:

• dizziness; or
• feeling tired.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Dosage Forms & Strengths

azilsartan/chlorthalidone

tablet

• 40mg/12.5mg
• 40mg/25mg

Hypertension

Angiotensin II receptor blocker (ARB) and thiazide-like diuretic combination 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

40 mg/12.5 mg PO qDay initially; may increase to 40 mg/25 mg after 2-4 weeks as needed to achieve blood pressure goals; not to exceed 40 mg/25 mg daily

Switching from ARB or diuretic monotherapy: Initiate with 40 mg/12.5 mg PO qDay

Renal & Hepatic Impairment

Renal impairment

• Mild-to-moderate (eGFR 30 mL/min/1.73 sq.meter or greater): No dose adjustment required
• Severe (eGFR <30 mL/min/1.73 sq.meter): Safety and effectiveness not established
• Chlorthalidone may precipitate azotemia

Hepatic impairment

• Mild-to-moderate: No dose adjustment required for azilsartan
• Severe: Azilsartan has not been studied in patients with severe hepatic impairment
• 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

Administration

Patients titrated to the individual components (ie, azilsartan and chlorthalidone) may instead receive the corresponding dose of Edarbyclor

Patients who experience dose-limiting adverse reactions on chlorthalidone monotherapy may be switched to Edarbyclor, initially with a lower dose of chlorthalidone

May be taken with or without food

Correct volume depletion prior to administration, particularly with impaired renal function or with high doses of diuretics

May be administered with other antihypertensive agents

Safety and efficacy not established

Black Box Warnings

When pregnancy is detected, discontinue as soon as possible; drugs affecting renin-angiotensin system causing oligohydramnios, which may result in fetal injury and/or death (also see Cautions)

Contraindications

Anuria

Do not coadminister aliskiren with ARBs or ACEIs in patients with diabetes

Cautions

Hyperuricemia

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

Fetal toxicity

• Also see Black Box Warnings
• 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
• 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 symptomatic hypotension may occur after initiation of treatment; such patients are probably not good candidates to start therapy with more than one drug
• Correct volume prior to administration; if hypotension does occur, place patient in supine position and, if necessary, give an IV infusion of normal saline
• 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 if progressive renal impairment becomes evident
• Azilsartan: Dual blockade of the renin angiotensin system with ARBs, ACE inhibitors, or aliskiren is associated with increased risk for hypotension, hyperkalemia, and renal function changes (including acute renal failure) compared to monotherapy
• 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
• May cause renal failure in patients with renal artery stenosis

Electrolytes

• Hypokalemia is a dose-dependent adverse reaction that may develop with chlorthalidone; Edarbyclor attenuates chlorthalidone-associated hypokalemia
• Coadministration of digitalis may exacerbate adverse effects of hypokalemia
• Thiazide diuretics can cause hyponatremia and hypokalemia; drugs that inhibit the renin angiotensin system can cause hyperkalemia; monitor serum electrolytes periodically