azilsartan/chlorthalidone (Rx)

Brand and Other Names:Edarbyclor
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Dosing & Uses

AdultPediatric

Dosing 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

Next:

Interactions

Interaction Checker

and azilsartan/chlorthalidone

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            Contraindicated (1)

            • aliskiren

              azilsartan decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ARBs in patients with diabetes; avoid coadministration with ARBs if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ARBS with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            Serious - Use Alternative (19)

            • aminolevulinic acid oral

              aminolevulinic acid oral, chlorthalidone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid administering other phototoxic drugs with aminolevulinic acid oral for 24 hr during perioperative period.

            • aminolevulinic acid topical

              chlorthalidone increases toxicity of aminolevulinic acid topical by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration of photosensitizing drugs may enhance the phototoxic reaction to photodynamic therapy with aminolevulinic acid.

            • benazepril

              azilsartan, benazepril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • captopril

              azilsartan, captopril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • enalapril

              azilsartan, enalapril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • fosinopril

              azilsartan, fosinopril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • isocarboxazid

              isocarboxazid, chlorthalidone. Other (see comment). Contraindicated. Comment: Additive hypotensive effects may be seen when MAOI's are combined with antihypertensives.

            • lisinopril

              azilsartan, lisinopril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • lithium

              azilsartan increases toxicity of lithium by decreasing renal clearance. Avoid or Use Alternate Drug.

            • lofexidine

              lofexidine, chlorthalidone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.

              lofexidine, azilsartan. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.

            • methyl aminolevulinate

              chlorthalidone, methyl aminolevulinate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

            • moexipril

              azilsartan, moexipril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • perindopril

              azilsartan, perindopril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • potassium phosphates, IV

              azilsartan and potassium phosphates, IV both increase serum potassium. Avoid or Use Alternate Drug.

            • quinapril

              azilsartan, quinapril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • ramipril

              azilsartan, ramipril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • squill

              chlorthalidone increases toxicity of squill by Other (see comment). Avoid or Use Alternate Drug. Comment: Potassium depletion may enhance toxicity of squill.

            • trandolapril

              azilsartan, trandolapril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • tretinoin

              chlorthalidone, tretinoin. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

            Monitor Closely (175)

            • acebutolol

              acebutolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • aceclofenac

              aceclofenac increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • acemetacin

              acemetacin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • albiglutide

              chlorthalidone decreases effects of albiglutide by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

              azilsartan increases effects of albiglutide by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

            • albuterol

              albuterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

            • amifostine

              amifostine, azilsartan. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration with blood pressure lowering agents may increase the risk and severity of hypotension associated with amifostine. When amifostine is used at chemotherapeutic doses, withhold blood pressure lowering medications for 24 hr prior to amifostine; if blood pressure lowering medication cannot be withheld, do not administer amifostine.

            • aldesleukin

              aldesleukin increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • amifostine

              amifostine, chlorthalidone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration with blood pressure lowering agents may increase the risk and severity of hypotension associated with amifostine. When amifostine is used at chemotherapeutic doses, withhold blood pressure lowering medications for 24 hr prior to amifostine; if blood pressure lowering medication cannot be withheld, do not administer amifostine.

            • amiloride

              amiloride increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • arformoterol

              arformoterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

            • aspirin

              aspirin, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              aspirin decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              aspirin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • aspirin rectal

              aspirin rectal decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              aspirin rectal increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

              aspirin rectal, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • aspirin/citric acid/sodium bicarbonate

              aspirin/citric acid/sodium bicarbonate decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              aspirin/citric acid/sodium bicarbonate, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              aspirin/citric acid/sodium bicarbonate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • atenolol

              atenolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • avanafil

              avanafil increases effects of azilsartan by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • avanafil

              avanafil increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • beclomethasone, inhaled

              beclomethasone, inhaled increases toxicity of chlorthalidone by increasing elimination. Use Caution/Monitor. May increase the hypokalemic effects of thiazide diuretics.

            • benazepril

              benazepril, chlorthalidone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Enhanced hypotensive effects. Increased risk of nephrotoxicity. Monitor blood pressure and renal function.

            • bendroflumethiazide

              bendroflumethiazide and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

            • betaxolol

              betaxolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • bisoprolol

              bisoprolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • bretylium

              azilsartan, bretylium. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Each drug may cause hypotension.

              chlorthalidone, bretylium. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Each drug may cause hypotension.

            • bumetanide

              bumetanide and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

            • canagliflozin

              azilsartan and canagliflozin both increase serum potassium. Use Caution/Monitor.

            • buprenorphine, long-acting injection

              buprenorphine, long-acting injection decreases effects of chlorthalidone by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Opioids can reduce diuretic efficacy by inducing antidiuretic hormone release.

            • calcifediol

              chlorthalidone increases toxicity of calcifediol by Other (see comment). Use Caution/Monitor. Comment: Thiazide diuretics may increase serum calcium by decreasing urinary calcium excretion.

            • candesartan

              candesartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • captopril

              captopril, chlorthalidone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Increased risk of nephrotoxicity. Monitor blood pressure and renal function.

            • carbenoxolone

              chlorthalidone and carbenoxolone both decrease serum potassium. Use Caution/Monitor.

            • carbidopa

              carbidopa increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.

            • carvedilol

              carvedilol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • celecoxib

              celecoxib decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              celecoxib increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              celecoxib, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • celiprolol

              celiprolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              chlorthalidone decreases levels of celiprolol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

            • choline magnesium trisalicylate

              choline magnesium trisalicylate, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              choline magnesium trisalicylate decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • chlorothiazide

              chlorothiazide and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

            • cholestyramine

              cholestyramine decreases levels of chlorthalidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

            • choline magnesium trisalicylate

              choline magnesium trisalicylate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

            • cornsilk

              cornsilk increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypokalemia (theoretical interaction).

            • cyclopenthiazide

              chlorthalidone and cyclopenthiazide both decrease serum potassium. Use Caution/Monitor.

            • dalteparin

              dalteparin increases toxicity of azilsartan by Other (see comment). Use Caution/Monitor. Comment: Low molecular weight heparins may suppress adrenal aldosterone secretion, which can potentially cause hyperkalemia.

            • deflazacort

              chlorthalidone and deflazacort both decrease serum potassium. Use Caution/Monitor.

            • dichlorphenamide

              dichlorphenamide and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

            • diclofenac

              diclofenac decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              azilsartan decreases effects of diclofenac by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              diclofenac, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              diclofenac increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • diflunisal

              diflunisal decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              diflunisal, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              diflunisal increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • digoxin

              digoxin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              chlorthalidone increases effects of digoxin by pharmacodynamic synergism. Use Caution/Monitor. Hypokalemia increases digoxin effects.

            • enoxaparin

              enoxaparin increases toxicity of azilsartan by Other (see comment). Use Caution/Monitor. Comment: Low molecular weight heparins may suppress adrenal aldosterone secretion, which can potentially cause hyperkalemia.

            • dobutamine

              dobutamine and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

            • dopexamine

              dopexamine and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

            • drospirenone

              drospirenone increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • empagliflozin

              empagliflozin, chlorthalidone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of empagliflozin with diuretics results in increased urine volume and frequency of voids, which might enhance the potential for volume depletion.

            • ephedrine

              ephedrine and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

            • epinephrine

              epinephrine and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

            • epinephrine racemic

              epinephrine racemic and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

            • eprosartan

              eprosartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • esmolol

              esmolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ethacrynic acid

              ethacrynic acid and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

            • etodolac

              etodolac increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              etodolac, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              etodolac decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • exenatide injectable solution

              azilsartan increases effects of exenatide injectable solution by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

              chlorthalidone decreases effects of exenatide injectable solution by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

            • exenatide injectable suspension

              azilsartan increases effects of exenatide injectable suspension by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

              chlorthalidone decreases effects of exenatide injectable suspension by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

            • fenoprofen

              fenoprofen increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              fenoprofen, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              fenoprofen decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • fentanyl

              fentanyl decreases effects of chlorthalidone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

            • flurbiprofen

              flurbiprofen, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              flurbiprofen decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • fentanyl intranasal

              fentanyl intranasal decreases effects of chlorthalidone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

            • fentanyl transdermal

              fentanyl transdermal decreases effects of chlorthalidone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

            • fentanyl transmucosal

              fentanyl transmucosal decreases effects of chlorthalidone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

            • flurbiprofen

              flurbiprofen increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • formoterol

              formoterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

            • furosemide

              furosemide and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

            • gentamicin

              chlorthalidone and gentamicin both decrease serum potassium. Use Caution/Monitor.

            • heparin

              heparin increases toxicity of azilsartan by Other (see comment). Use Caution/Monitor. Comment: Low molecular weight heparins may suppress adrenal aldosterone secretion, which can potentially cause hyperkalemia.

            • hydrochlorothiazide

              chlorthalidone and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • ibuprofen

              ibuprofen, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              ibuprofen decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              ibuprofen increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ibuprofen IV

              ibuprofen IV increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. NSAIDs may decrease the therapeutic effects of thiazide-like diuretics; may also enhance nephrotoxic effects.

              ibuprofen IV decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              ibuprofen IV, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              chlorthalidone will increase the level or effect of ibuprofen IV by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • indacaterol, inhaled

              chlorthalidone, indacaterol, inhaled. serum potassium. Use Caution/Monitor. Combination may increase risk of hypokalemia.

              indacaterol, inhaled, chlorthalidone. Other (see comment). Use Caution/Monitor. Comment: Caution is advised in the coadministration of indacaterol neohaler with non-potassium-sparing diuretics.

            • indomethacin

              indomethacin, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              indomethacin decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • indapamide

              chlorthalidone and indapamide both decrease serum potassium. Use Caution/Monitor.

            • indomethacin

              indomethacin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • insulin aspart

              azilsartan increases effects of insulin aspart by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin aspart protamine/insulin aspart

              azilsartan increases effects of insulin aspart protamine/insulin aspart by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin degludec

              azilsartan increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

              chlorthalidone decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

              azilsartan, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

            • insulin degludec/insulin aspart

              chlorthalidone decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

              azilsartan, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

            • insulin detemir

              azilsartan increases effects of insulin detemir by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin inhaled

              chlorthalidone decreases effects of insulin inhaled by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

            • insulin glargine

              azilsartan increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin glulisine

              azilsartan increases effects of insulin glulisine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin inhaled

              azilsartan, insulin inhaled. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              azilsartan increases effects of insulin inhaled by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin isophane human/insulin regular human

              azilsartan increases effects of insulin isophane human/insulin regular human by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin lispro

              azilsartan increases effects of insulin lispro by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin lispro protamine/insulin lispro

              azilsartan increases effects of insulin lispro protamine/insulin lispro by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin NPH

              azilsartan increases effects of insulin NPH by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin regular human

              azilsartan increases effects of insulin regular human by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • irbesartan

              irbesartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • isoproterenol

              isoproterenol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

            • juniper

              juniper, chlorthalidone. Other (see comment). Use Caution/Monitor. Comment: Juniper may potentiate or interfere with diuretic therapy. Juniper has diuretic effects, but may cause kidney damage at large doses.

            • ketoprofen

              ketoprofen increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              ketoprofen, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              ketoprofen decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • ketorolac

              ketorolac, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              ketorolac decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              ketorolac increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ketorolac intranasal

              ketorolac intranasal increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

            • liraglutide

              azilsartan increases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

            • labetalol

              labetalol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • levalbuterol

              levalbuterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

            • levodopa

              levodopa increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

            • lily of the valley

              chlorthalidone increases toxicity of lily of the valley by Other (see comment). Use Caution/Monitor. Comment: Increased risk of cardiac toxicity due to K+ depletion.

            • liraglutide

              chlorthalidone decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

            • lithium

              chlorthalidone increases toxicity of lithium by decreasing elimination. Use Caution/Monitor.

            • lornoxicam

              lornoxicam increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • losartan

              losartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • lurasidone

              lurasidone increases effects of chlorthalidone by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of hypotension with concurrent use. Monitor blood pressure and adjust dose of antihypertensive agent as needed.

            • maitake

              maitake increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypokalemia (theoretical interaction).

            • maraviroc

              maraviroc, chlorthalidone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.

              maraviroc, azilsartan. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.

            • meclofenamate

              meclofenamate decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              meclofenamate, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              meclofenamate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • mefenamic acid

              mefenamic acid, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              mefenamic acid decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              mefenamic acid increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • meloxicam

              meloxicam, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              meloxicam decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              meloxicam increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • metaproterenol

              metaproterenol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

            • methylphenidate

              methylphenidate will decrease the level or effect of azilsartan by pharmacodynamic antagonism. Use Caution/Monitor. Methylphenidate may diminish antihypertensive effects. Monitor BP.

            • methoxsalen

              methoxsalen, chlorthalidone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive photosensitizing effects.

            • methyclothiazide

              chlorthalidone and methyclothiazide both decrease serum potassium. Use Caution/Monitor.

            • metolazone

              chlorthalidone and metolazone both decrease serum potassium. Use Caution/Monitor.

            • metoprolol

              metoprolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • mometasone inhaled

              mometasone inhaled increases toxicity of chlorthalidone by Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may increase hypokalemic effect of loop diuretics.

            • mycophenolate

              chlorthalidone will increase the level or effect of mycophenolate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • nabumetone

              nabumetone, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              nabumetone increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              nabumetone decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • nadolol

              nadolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • naproxen

              naproxen, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              naproxen decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • naproxen

              naproxen increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • nebivolol

              nebivolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • nitazoxanide

              nitazoxanide, chlorthalidone. Either increases levels of the other by Mechanism: plasma protein binding competition. Use Caution/Monitor.

            • nitroglycerin rectal

              nitroglycerin rectal, azilsartan. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Observe for possible additive hypotensive effects during concomitant use. .

              nitroglycerin rectal, chlorthalidone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Observe for possible additive hypotensive effects during concomitant use. .

            • norepinephrine

              norepinephrine and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

            • oxaprozin

              oxaprozin, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              oxaprozin decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • oliceridine

              oliceridine decreases effects of chlorthalidone by Other (see comment). Use Caution/Monitor. Comment: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Monitor for signs of diminished diuresis and/or effects on blood pressure and increase dosage of the diuretic as needed. .

            • olmesartan

              olmesartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • olodaterol inhaled

              chlorthalidone and olodaterol inhaled both decrease serum potassium. Use Caution/Monitor.

            • ospemifene

              chlorthalidone, ospemifene. Either increases levels of the other by plasma protein binding competition. Modify Therapy/Monitor Closely.

            • oxaprozin

              oxaprozin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • parecoxib

              parecoxib increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • penbutolol

              penbutolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pindolol

              pindolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pirbuterol

              pirbuterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

            • piroxicam

              piroxicam increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              piroxicam, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              piroxicam decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • pivmecillinam

              pivmecillinam, chlorthalidone. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • potassium citrate/citric acid

              azilsartan and potassium citrate/citric acid both increase serum potassium. Use Caution/Monitor.

            • porfimer

              chlorthalidone, porfimer. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced photosensitivity.

            • potassium acid phosphate

              potassium acid phosphate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • potassium chloride

              potassium chloride increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • potassium citrate

              potassium citrate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • potassium iodide

              potassium iodide and azilsartan both increase serum potassium. Use Caution/Monitor. Potassium salts may increase the hyperkalemic effects of ARBs; the effect may be the result of aldosterone suppression in patients receiving ARBs.

            • probenecid

              chlorthalidone will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • propranolol

              propranolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • sacubitril/valsartan

              sacubitril/valsartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • salicylates (non-asa)

              salicylates (non-asa) increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • salmeterol

              salmeterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

            • salsalate

              salsalate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              salsalate decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              salsalate, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • shark cartilage

              chlorthalidone, shark cartilage. Other (see comment). Use Caution/Monitor. Comment: May lead to hypercalcemia (theoretical).

            • sodium sulfate/?magnesium sulfate/potassium chloride

              sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of azilsartan by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

            • sodium sulfate/?magnesium sulfate/potassium chloride

              sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of chlorthalidone by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

            • sodium sulfate/potassium sulfate/magnesium sulfate

              sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of chlorthalidone by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

              sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of azilsartan by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

            • sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol

              chlorthalidone and sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol both decrease serum potassium. Modify Therapy/Monitor Closely.

            • sulfasalazine

              sulfasalazine, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              sulfasalazine decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • sotalol

              sotalol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • spironolactone

              spironolactone increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • succinylcholine

              succinylcholine increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • sulfasalazine

              sulfasalazine increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • sulindac

              sulindac, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              sulindac decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              sulindac increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • synthetic human angiotensin II

              azilsartan decreases effects of synthetic human angiotensin II by pharmacodynamic antagonism. Use Caution/Monitor.

            • tadalafil

              tadalafil increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • tadalafil

              tadalafil increases effects of azilsartan by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • telmisartan

              telmisartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • temocillin

              temocillin, chlorthalidone. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • terbutaline

              terbutaline and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

            • ticarcillin

              ticarcillin, chlorthalidone. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • timolol

              timolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • tolfenamic acid

              tolfenamic acid increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • tolmetin

              tolmetin, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              tolmetin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              tolmetin decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • tolvaptan

              tolvaptan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • voclosporin

              voclosporin and azilsartan both increase serum potassium. Use Caution/Monitor.

              voclosporin, azilsartan. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.

            Minor (46)

            • acarbose

              chlorthalidone decreases effects of acarbose by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • aceclofenac

              chlorthalidone will increase the level or effect of aceclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • acemetacin

              chlorthalidone will increase the level or effect of acemetacin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • acyclovir

              chlorthalidone will increase the level or effect of acyclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • agrimony

              agrimony increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.

            • albuterol

              albuterol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • aminohippurate sodium

              chlorthalidone will increase the level or effect of aminohippurate sodium by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • arformoterol

              arformoterol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • aspirin

              chlorthalidone will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • aspirin rectal

              chlorthalidone will increase the level or effect of aspirin rectal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • aspirin/citric acid/sodium bicarbonate

              chlorthalidone will increase the level or effect of aspirin/citric acid/sodium bicarbonate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • balsalazide

              chlorthalidone will increase the level or effect of balsalazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • bendroflumethiazide

              bendroflumethiazide will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • birch

              birch increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.

            • bitter melon

              bitter melon, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • brimonidine

              brimonidine increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.

            • budesonide

              budesonide, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • calcitriol topical

              calcitriol topical, chlorthalidone. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential additive hypercalcemia.

            • calcium acetate

              chlorthalidone increases levels of calcium acetate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

            • calcium carbonate

              chlorthalidone increases levels of calcium carbonate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

            • calcium chloride

              chlorthalidone increases levels of calcium chloride by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

            • calcium citrate

              chlorthalidone increases levels of calcium citrate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

            • calcium gluconate

              chlorthalidone increases levels of calcium gluconate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

            • carbenoxolone

              chlorthalidone, carbenoxolone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypokalemic effects.

            • cefadroxil

              cefadroxil will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cefamandole

              cefamandole will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cefpirome

              cefpirome will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • celecoxib

              chlorthalidone will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cephalexin

              cephalexin will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • chlorothiazide

              chlorothiazide will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • chlorpropamide

              chlorthalidone will increase the level or effect of chlorpropamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              chlorthalidone decreases effects of chlorpropamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • choline magnesium trisalicylate

              chlorthalidone will increase the level or effect of choline magnesium trisalicylate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • colestipol

              colestipol decreases levels of chlorthalidone by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • corticotropin

              corticotropin, chlorthalidone. pharmacodynamic synergism. Minor/Significance Unknown. Possible enhanced electrolyte loss.

            • cortisone

              cortisone, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • cosyntropin

              cosyntropin, chlorthalidone. pharmacodynamic synergism. Minor/Significance Unknown. Possible enhanced electrolyte loss.

            • cyclopenthiazide

              chlorthalidone will increase the level or effect of cyclopenthiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • deflazacort

              deflazacort, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • dexamethasone

              dexamethasone, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • diazoxide

              diazoxide, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hyperglycemia.

            • diclofenac

              chlorthalidone will increase the level or effect of diclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • diflunisal

              chlorthalidone will increase the level or effect of diflunisal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • dobutamine

              dobutamine, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • dopexamine

              dopexamine, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • entecavir

              azilsartan, entecavir. Either increases effects of the other by decreasing renal clearance. Minor/Significance Unknown. Coadministration with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of either entecavir or the coadministered drug.

            • ephedrine

              ephedrine, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

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            Adverse Effects

            1-10%

            Dizziness (8.9%)

            Fatigue (2%)

            Hypotension (1.7%)

            <1%

            Syncope (0.3%)

            Postmarketing Reports

            Nausea

            Rash, pruritus, angioedema

            Loss of consciousness

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            Warnings

            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

            Coadministration with aliskiren-containing products 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

            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

            Impaired renal function

            • Monitor for worsening renal function in patients with renal impairment; consider withholding or discontinuing if progressive renal impairment becomes evident
            • May cause renal failure in patients with renal artery stenosis
            • 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
              • As a consequence of inhibiting the renin-angiotensin system, changes in renal function may be anticipated in susceptible individuals receiving therapy
              • In patients whose renal function may depend on activity of renin-angiotensin system (eg, 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 receiving therapy
            • 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
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            Pregnancy & Lactation

            Pregnancy

            Drug can cause fetal harm when administered to a pregnant woman; use of drugs that act on renin-angiotensin system during second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death; most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in first trimester have not distinguished drugs affecting renin-angiotensin system from other antihypertensive agents; when pregnancy is detected, discontinue drug as soon as possible

            Hypertension in pregnancy increases maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (eg, need for cesarean section and post-partum hemorrhage); hypertension increases fetal risk for intrauterine growth restriction and intrauterine death; pregnant women with hypertension should be carefully monitored and managed accordingly

            Oligohydramnios in pregnant women who use drugs affecting renin-angiotensin system in the second and third trimesters can result in reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension and death

            Perform serial ultrasound examinations to assess the intra-amniotic environment; closely observe infants with histories of in utero exposure to drug for hypotension, oliguria, and hyperkalemia; in neonates with a history of in utero exposure to drug, if oliguria or hypotension occurs, support blood pressure and renal perfusion; exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function

            Thiazides cross the placenta; use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice, thrombocytopenia, and possible other adverse reactions that have occurred in adults

            Lactation

            There is limited information regarding presence of azilsartan in human milk, effects on breastfed infant, or on milk production; azilsartan is present in rat milk; thiazide-like diuretics like chlorthalidone are excreted in human milk; because of potential for adverse effects on nursing infant, advise a nursing woman that breastfeeding is not recommended during therapy

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Angiotensin II blocker; displaces angiotensin II from AT1 receptor and may lower blood pressure by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water absorption, and hypertrophic responses

            Chlorthalidone produces diuresis with increased excretion of sodium and chloride at the cortical diluting segment of the ascending limb of Henle’s loop of the nephron

            Pharmacokinetics

            Bioavailability: 60% (azilsartan)

            Onset: 2.6 hr (chlorthalidone)

            Duration: Up to 72 hr (chlorthalidone)

            Peak Plasma Time: 3 hr (azilsartan); 1 hr (chlorthalidone)

            Protein Bound: >99%, mainly to albumin (azilsartan); 75% bound to plasma protein and 58% of drug bound to albumin (chlorthalidone)

            Chlorthalidone binding (whole blood): Predominantly bound to erythrocyte carbonic anhydrase

            Vd: 16 L (azilsartan)

            Half-life, elimination: 11-12 hr (azilsartan); 45 hr (chlorthalidone)

            Renal clearance: 2.3 mL/min (azilsartan)

            Excretion (azilsartan medoxomil): Feces 55%, urine 42%; active metabolite (azilsartan) 15% excreted in urine

            Excretion (chlorthalidone): Major portion of drug excreted unchanged by the kidneys; nonrenal routes not clarified

            Metabolism

            • Azilsartan medoxomil is rapidly hydrolyzed to azilsartan, the active metabolite, in the GI tract during absorption
            • Azilsartan metabolites: major metabolite in plasma is formed by O-dealkylation, referred to as metabolite M-II, and the minor metabolite is formed by decarboxylation, referred to as metabolite M-I; these do no contribute to the pharmacologic activity
            • Metabolized by: CYP2C9 (azilsartan)
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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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            Code Definition
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.