Candesartan

Pharmacologic Category

Angiotensin II Receptor Blocker; Antihypertensive

Dosing: Adult

Acute coronary syndromes: Note: May be used as an alternative in patients who cannot tolerate an angiotensin-converting enzyme (ACE) inhibitor (eg, due to cough) (ACC/AHA [Amsterdam 2014; O'Gara 2013]; Guyer 2019). In patients with prior ACE inhibitor-associated angioedema (ie, without urticaria or other signs of hypersensitivity), an angiotensin II receptor blocker (ARB) may also be an alternative. ARBs do not appear to elevate the risk of angioedema (Rasmussen 2019; Toh 2012); however, patients must be educated that angioedema due to an ACE inhibitor can sometimes reoccur within months following discontinuation (Beltrami 2011); referral to an allergist may be appropriate.

Non-ST-elevation acute coronary syndrome (alternative agent) (off-label use): Note: Patients should be hemodynamically stable before initiation. Use as a component of an appropriate medical regimen, which may also include antiplatelet agent(s), a beta-blocker, and a statin. Continue ARB therapy indefinitely for patients with concurrent diabetes, left ventricular ejection fraction ≤40%, hypertension, or stable chronic kidney disease (CKD) (AHA/ACC [Amsterdam 2014]). Dosing is based on general dosing range in the manufacturer's labeling.

Oral: Initial: 8 mg once daily; increase dose as tolerated up to 32 mg/day under close monitoring to avoid hypotension.

ST-elevation myocardial infarction (alternative agent) (off-label use): Note: Patients should be hemodynamically stable before initiation. Use as a component of an appropriate medical regimen, which may also include antiplatelet agent(s), a beta-blocker, and a statin. Continue ARB therapy indefinitely (ACC/AHA [O'Gara 2013]). Dosing is based on general dosing range in the manufacturer's labeling.

Oral: Initial: 8 mg once daily; increase dose as tolerated up to 32 mg/day under close monitoring to avoid hypotension.

Heart failure with reduced ejection fraction: Note: May be used as an alternative in patients who cannot tolerate an ACE inhibitor (eg, due to cough) (ACC/AHA/HFSA [Yancy 2017]; Guyer 2019). In patients with prior ACE inhibitor- or angiotensin receptor-/neprilysin inhibitor-associated angioedema (ie, without urticaria or other signs of hypersensitivity), candesartan may be an alternative (Meyer 2019); however, use in this situation should only occur under the care of a heart failure specialist. ARBs do not appear to elevate the risk of angioedema (Rasmussen 2019; Toh 2012); however, patients must be educated that angioedema due to an ACE inhibitor can sometimes reoccur within months following discontinuation (Beltrami 2011); referral to an allergist may be appropriate.

Oral: Initial: 4 to 8 mg once daily; increase the dose every 2 weeks based on response and tolerability; target dose: 32 mg once daily (ACC/AHA [Yancy 2017]; Meyer 2019).

Hypertension: Note: For initial treatment in patients with blood pressure ≥20/10 mm Hg above goal, may be used in combination with another appropriate agent (eg, long-acting dihydropyridine calcium channel blocker, thiazide diuretic). For patients <20/10 mm Hg above goal, some experts recommend an initial trial of monotherapy; however, over time, many patients will require combination therapy (ACC/AHA [Whelton 2018]; Mann 2019a).

Oral: Initial: 8 mg once daily; evaluate response every 4 to 6 weeks and increase dose as needed up to 32 mg once daily (ACC/AHA [Whelton 2018]; Mann 2019a).

Proteinuric chronic kidney disease (diabetic or nondiabetic) (off-label use): Note: In nondiabetic and type 2 diabetic proteinuric CKD, an ARB or an ACE inhibitor may be used. In type 1 diabetic proteinuric CKD, an ARB may be used as an alternative in patients who cannot tolerate an ACE inhibitor (eg, due to cough) (Bakris 2019; Mann 2019b, McCulloch 2019). In patients with prior ACE inhibitor-associated angioedema (ie, without urticaria or other signs of hypersensitivity), candesartan may be an alternative. ARBs do not appear to elevate the risk of angioedema (Rasmussen 2019; Toh 2012); however, patients must be educated that angioedema due to an ACE inhibitor can sometimes reoccur within months following discontinuation (Beltrami 2011); referral to an allergist may be appropriate. Dosing is based on general dosing range in the manufacturer's labeling.

Oral: Initial: 8 mg once daily; can be increased to 32 mg once daily based on blood pressure response and tolerability. Target to an appropriate blood pressure goal and a proteinuria goal of <1 g/day (KDIGO 2013; Mann 2019b).

IgA nephropathy: In addition to an appropriate blood pressure goal, a proteinuria goal of <1 g/day is also generally recommended (KDIGO 2012). Some experts treat to a proteinuria goal of <500 mg/day. If proteinuria goal is not met with monotherapy at the maximum dose, consider adding other modalities and/or agents (Cattran 2019).

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

Adults: No initial dosage adjustment necessary; however, in patients with severe renal impairment (CrCl <30 mL/minute/1.73 m²) AUC and C_max were approximately doubled after repeated dosing.

Dosing: Hepatic Impairment: Adult

Mild impairment (Child-Pugh class A): No initial dosage adjustment necessary.

Moderate impairment (Child-Pugh class B): Initial: 8 mg daily (AUC increased by 145%) in adult patients with hypertension.

Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, systemic exposure increases significantly in moderate impairment.

Dosing: Pediatric

Note: Use of a lower initial dose is recommended in volume- and salt-depleted patients; if possible, correct volume depletion prior to administration; dosage must be individualized

Hypertension:

Children 1 to <6 years: Oral: Initial: 0.2 mg/kg/day once daily; titrate to response (within 2 weeks, antihypertensive effect usually observed); usual range: 0.05 to 0.4 mg/kg/day divided once or twice daily; maximum daily dose: 0.4 mg/kg/day; higher doses have not been studied.

Children and Adolescents 6 to <17 years: Oral:

<50 kg: Initial: 4 to 8 mg/day once daily; titrate to response (within 2 weeks, antihypertensive effect usually observed); usual range: 2 to 16 mg/day divided once or twice daily; maximum daily dose: 32 mg/day; higher doses have not been studied.

>50 kg: Initial: 8 to 16 mg/day once daily; titrate to response (within 2 weeks, antihypertensive effect usually observed); usual range: 4 to 32 mg/day divided once or twice daily; maximum daily dose: 32 mg/day; higher doses have not been studied.

Adolescents ≥17 years: Oral: Initial: 16 mg once daily; titrate to response (within 2 weeks, antihypertensive effect usually observed; maximum effect seen within 4 to 6 weeks); usual range: 8 to 32 mg/day divided once or twice daily; blood pressure response is dose-related over the range of 2 to 32 mg; larger doses do not appear to have a greater effect and there is relatively little experience with such doses

Dosing: Renal Impairment: Pediatric

Children and Adolescents 1 to <17 years:

CrCl ≥30 mL/minute/1.73 m²: There are no dosage adjustments provided in the manufacturer's labeling; has not been studied in pediatric patients with renal impairment.

CrCl <30 mL/minute/1.73 m²: Use is not recommended (has not been studied).

Not removed by dialysis.

Dosing: Hepatic Impairment: Pediatric

Mild hepatic impairment (Child-Pugh Class A): No initial dosage adjustment required

Moderate hepatic impairment (Child-Pugh Class B): There are no dosage adjustments provided in the manufacturer’s labeling for pediatric patients.

Severe hepatic impairment (Child-Pugh Class C): There are no dosage adjustments provided in manufacturer's labeling (has not been studied); however, systemic exposure increases significantly in moderate impairment.

Calculations

Use: Labeled Indications

Heart failure with reduced ejection fraction: Treatment of heart failure (NYHA class II to IV) in adults with left ventricular systolic dysfunction (ejection fraction <40%) to reduce cardiovascular death and heart failure hospitalization.

Hypertension: Management of hypertension in adults and children ≥1 year of age.

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

Non-ST-elevation acute coronary syndromeLevel of Evidence [G]

Based on the 2014 American Heart Association/American College of Cardiology (AHA/ACC) guidelines for the management of patients with non-ST-elevation acute coronary syndromes, an angiotensin II receptor blocker (ARB) is recommended and effective in patients who have indications for but are intolerant of angiotensin-converting enzyme (ACE) inhibitors; this includes patients with hypertension, diabetes, stable chronic kidney disease (CKD), heart failure, or myocardial infarction who have a left ventricular ejection fraction ≤40%.

Proteinuric chronic kidney disease (diabetic or nondiabetic)Level of Evidence [G]

Based on the 2012 Kidney Disease Improving Global Outcomes guidelines, the use of an ACE inhibitor or an ARB is recommended in patients with proteinuric CKD to prevent progression of CKD.

ST-elevation myocardial infarctionLevel of Evidence [G]

Based on the 2013 ACC/AHA guidelines for the management of patients with ST-elevation acute coronary syndromes, an ARB is recommended and effective in patients who have indications for but are intolerant of ACE inhibitors.

Level of Evidence Definitions

Level of Evidence Scale

Class and Related Monographs

Angiotensin II Receptor Antagonists

Clinical Practice Guidelines

Atrial Fibrillation:

AHA/ACC/HRS, "2014 AHA/ACC/HRS Guideline for the Management of Patients with Atrial Fibrillation," March 2014

Chronic Kidney Disease:

KDIGO 2012 Clinical Practice Guidelines for the Evaluation and Management of Chronic Kidney Disease, January 2013

Coronary Artery Bypass Graft Surgery:

“2011 ACC/AHA Guideline for Coronary Artery Bypass Graft Surgery,” November 2011

AHA Scientific Statement, "Secondary Prevention After Coronary Artery Bypass Graft Surgery,” February 2015

Diabetes Mellitus:

AACE/ACE, “Consensus Statement on the Comprehensive Type 2 Diabetes Management Algorithm - 2019 Executive Summary,” January 2019

ADA, “Standards of Medical Care in Diabetes - 2020,” January 2020

Diabetes Canada, “Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada,” 2018

Heart Failure:

ACC/AHA, “2013 ACC/AHA Guideline for the Management of Heart Failure,” June 2013

ACC/AHA/HFSA, “2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure,” May 2016

Canadian Cardiovascular Society, “2012 Heart Failure Management Guidelines Update: Focus on Acute and Chronic Heart Failure,” 2012

“HFSA 2010 Comprehensive Heart Failure Practice Guideline,” July 2010

Hypertension:

"2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults," November 2017.

AHA/ACC/ASH, “Treatment of Hypertension in Patients with Coronary Artery Disease: A Scientific Statement by the American Heart Association, American College of Cardiology and American Society of Hypertension,” May 2015

"ACC/AHA Expert Consensus Document on Hypertension in the Elderly," 2011

AHA/ACC/CDC, “AHA/ACC/CDC Science Advisory: An Effective Approach to High Blood Pressure Control” November 2013

ASH/ISH, “Clinical Practice Guidelines for the Management of Hypertension in the Community: A Statement by the American Society of Hypertension and the International Society of Hypertension,” January 2014

Eighth Joint National Committee (JNC 8), "2014 Evidence-based Guideline for the Management of High Blood Pressure in Adults," December 2013

Ischemic Heart Disease:

ACC/AHA/AATS/PCNA/SCAI/STS, "2014 Focused Update of the Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease," July 2014

ACC/AHA/ACP/AATS/PCNA/SCAI/STS, “2012 Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease,” November 2012

AHA/ACC, "2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes,” September 2014

ACC/AHA “2013 guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines”, January 2013

Peripheral Arterial Disease:

2011 ACC/AHA Focused Update of the Guideline for the Management of Patients with Peripheral Artery Disease (Updating the 2005 Guideline),” September 2011

Prevention:

“AHA/ACC Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and Other Atherosclerotic Vascular Disease: 2011 Update,” November 2011

Surgery:

ACC/AHA, “2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery,” August 2014

Valvular Heart Disease:

AHA/ACC, “2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease,” March 2014

Administration: Oral

Administer without regard to meals. An oral suspension may be prepared for children unable to swallow tablets (refer to Extemporaneously Prepared information).

Administration: Pediatric

Oral: May be administered without regard to meals. An oral suspension may be prepared for children unable to swallow tablets (refer to Extemporaneous Preparation information).

Storage/Stability

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Extemporaneously Prepared

Oral suspension may be made in concentrations ranging from 0.1 to 2 mg/mL; typically 1 mg/mL oral suspension suitable for majority of prescribed doses; any strength tablet may be used. A 1 mg/mL (total volume: 160 mL) oral suspension may be made with tablets and a 1:1 mixture of Ora-Plus® and Ora-Sweet SF®. Prepare the vehicle by adding 80 mL of Ora-Plus® and 80 mL of Ora-Sweet SF® or, alternatively, use 160 mL of Ora-Blend SF®. Add a small amount of vehicle to five 32 mg tablets and grind into a smooth paste using a mortar and pestle. Transfer the paste to a calibrated amber PET bottle, rinse the mortar and pestle clean using the vehicle, add this to the bottle, and then add a quantity of vehicle sufficient to make 160 mL. The suspension is stable at room temperature for 100 days unopened or 30 days after the first opening; do not freeze; label “shake well before use.” (Atacand prescribing information, 2013).

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat high blood pressure.

• It is used to treat heart failure (weak heart).

• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Back pain

• Flu-like symptoms

• Common cold symptoms

• Sore throat

• Stuffy nose

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain

• High potassium like abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, numbness or tingling feeling

• Severe dizziness

• Passing out

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Sound-alike/look-alike issues:

Contraindications

Hypersensitivity to candesartan or any component of the formulation; concomitant use with aliskiren in patients with diabetes mellitus

Documentation of allergenic cross-reactivity for angiotensin II receptor blockers is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Canadian labeling: Additional contraindications (not in US labeling): Concomitant use with aliskiren in patients with moderate-to-severe renal impairment (GFR <60 mL/minute/1.73 m²); pregnancy; breastfeeding; children <1 year of age; rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption

Warnings/Precautions

Concerns related to adverse effects:

• Angioedema: Angiotensin II receptor antagonists (ARBs) do not appear to elevate the risk of angioedema (Rasmussen 2019; Toh 2012). Patients with a history of angioedema due to an angiotensin-converting enzyme (ACE) inhibitor must be educated that sometimes there can be recurrence within months following discontinuation (Beltrami 2011). No matter the cause of angioedema, prolonged frequent monitoring is required, especially if tongue, glottis, or larynx are involved, as they are associated with airway obstruction. Discontinue therapy immediately if angioedema occurs. Aggressive early management is critical. IM administration of epinephrine may be necessary. Do not readminister the ARB to patients who experience angioedema from this medication.

• Hyperkalemia: May occur; risk factors include renal dysfunction, diabetes mellitus, concomitant use of potassium-sparing diuretics, potassium supplements and/or potassium containing salts. Use cautiously, if at all, with these agents and monitor potassium closely.

• Hypotension: Symptomatic hypotension may occur upon initiation in patients who are salt- or volume-depleted (eg, those treated with high-dose diuretics). Consider lower initial dosages in volume depleted patients; if possible, correct volume depletion prior to administration. This transient hypotensive response is not a contraindication to further treatment with candesartan.

• Renal function deterioration: May be associated with deterioration of renal function and/or increases in serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure) whose GFR is dependent on efferent arteriolar vasoconstriction by angiotensin II; deterioration may result in oliguria, acute renal failure, and progressive azotemia. Small increases in serum creatinine may occur following initiation; consider discontinuation only in patients with progressive and/or significant deterioration in renal function.

Disease-related concerns:

• Aortic/mitral stenosis: Use caution in patients with significant aortic/mitral stenosis.

• Ascites: Avoid use in patients with ascites due to cirrhosis or refractory ascites; if use cannot be avoided in patients with ascites due to cirrhosis, monitor blood pressure and renal function carefully to avoid rapid development of renal failure (AASLD [Runyon 2012]).

• Heart failure: Use caution when initiating in heart failure; may need to adjust dose, and/or concurrent diuretic therapy, because of candesartan-induced hypotension.

• Hepatic impairment: Systemic exposure increases in hepatic impairment. US manufacturer labeling recommends a dosage adjustment in patients with moderate hepatic impairment. Pharmacokinetics have not been studied in severe hepatic impairment.

• Renal artery stenosis: Use candesartan with caution in patients with unstented unilateral/bilateral renal artery stenosis. When unstented bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in renal function unless possible benefits outweigh risks.

• Renal impairment: Use with caution with preexisting renal insufficiency. Pediatric patients with a GFR <30 mL/minute/1.73 m² should not receive candesartan; has not been evaluated.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Pediatric: Avoid use in infants <1 year of age due to potential effects on the development of immature kidneys.

• Pregnancy: [US Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.

• Surgical patients: In patients on chronic ARB therapy, intraoperative hypotension may occur with induction and maintenance of general anesthesia; however, discontinuation of therapy prior to surgery is controversial. If continued preoperatively, avoidance of hypotensive agents during surgery is prudent (Hillis 2011). Based on current research and clinical guidelines in patients undergoing non-cardiac surgery, continuing ARBs is reasonable in the perioperative period. If ARBs are held before surgery, it is reasonable to restart postoperatively as soon as clinically feasible (ACC/AHA [Fleisher 2014]).

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

High concentrations occur in the elderly compared to younger subjects. AUC may be doubled in patients with renal impairment. No initial dose adjustment necessary since repeated dose did not demonstrate accumulation of drug or metabolites in elderly.

The AHA/ACC/ASH 2015 scientific statement on the treatment of hypertension in patients with CAD warns to use caution to avoid decreases in DBP <60 mm Hg especially in patients >60 years of age since reduced coronary perfusion may occur. When lowering SBP in older hypertensive patients with wide pulse pressures, very low DBP values (<60 mm Hg) may result. In patients with obstructive CAD, clinicians should lower blood pressure slowly and carefully monitor for any untoward signs or symptoms, especially those resulting from myocardial ischemia and worsening heart failure (AHA/ACC/ASH [Rosendorff 2015]).

Pregnancy Risk Factor

Pregnancy Considerations

[US Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. When pregnancy is detected, discontinue as soon as possible. The use of drugs which act on the renin-angiotensin system are associated with oligohydramnios. Oligohydramnios, due to decreased fetal renal function, may lead to fetal lung hypoplasia and skeletal malformations. Oligohydramnios may not appear until after irreversible fetal injury has occurred. Use in pregnancy is also associated with anuria, hypotension, renal failure, skull hypoplasia, and death in the fetus/neonate. The exposed fetus should be monitored for fetal growth, amniotic fluid volume, and organ formation. Infants exposed in utero should be monitored for hyperkalemia, hypotension, and oliguria (exchange transfusions or dialysis may be needed). These adverse events are generally associated with maternal use in the second and third trimesters.

Chronic maternal hypertension itself is also associated with adverse events in the fetus/infant. The risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death may be increased with chronic hypertension in pregnancy. Actual risks may be related to duration and severity of maternal hypertension (ACOG 203 2019).

The use of angiotensin II receptor blockers is generally not recommended to treat chronic hypertension in pregnant women and should generally be avoided in women planning a pregnancy (ACOG 203 2019). When treatment is needed in females of reproductive potential with diabetic nephropathy, candesartan should be discontinued at the first positive pregnancy test (Cabiddu 2016; Porta 2011).

Breast-Feeding Considerations

Candesartan is present in breast milk.

Transfer of candesartan in breast milk was evaluated in three postpartum women. The maternal dose in case one was candesartan 32 mg once daily (2.5 months' postpartum), and in cases two and three the dose was candesartan 8 mg once daily (8 and 13 months' postpartum). All three mothers had been treated for at least 2 weeks prior to the study. The maximum breast milk concentration occurred ~7 to 9 hours following the maternal dose. Candesartan was not measurable (<0.2 mcg/L) in the infant serum in cases two and three (sampling occurred ~2 to 3 hours after the maternal dose and was not evaluated in case one). In all three cases, the authors calculated the relative infant dose to be <1% of the weight-adjusted maternal dose (Coberger 2019).

Due to the potential for serious adverse reactions in the breastfeeding infant, the manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, considering the importance of treatment to the mother. In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).

Briggs' Drugs in Pregnancy & Lactation

Candesartan Cilexetil

Adverse Reactions

>10%:

Cardiovascular: Hypotension (19%)

Renal: Renal function abnormality (13%)

1% to 10%:

Central nervous system: Dizziness (4%)

Endocrine & metabolic: Hyperkalemia (6%)

Neuromuscular & skeletal: Back pain (3%)

Respiratory: Upper respiratory tract infection (6%), pharyngitis (2%), rhinitis (2%)

Frequency not defined:

Central nervous system: Headache

Renal: Exacerbation of renal disease (children & adolescents), increased serum creatinine

<1%, postmarketing, and/or case reports: Abnormal hepatic function tests, agranulocytosis, angioedema, cough, hepatitis, hyponatremia, leukopenia, neutropenia, pruritus, skin rash, urticaria

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

Angiotensin Receptor Antagonist Allergy/Hypersensitivity

Toxicology

Angiotensin II Receptor Blockers

Metabolism/Transport Effects

Substrate of CYP2C9 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions Open Interactions

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Aliskiren: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Aliskiren may enhance the hypotensive effect of Angiotensin II Receptor Blockers. Aliskiren may enhance the nephrotoxic effect of Angiotensin II Receptor Blockers. Management: Aliskiren use with ACEIs or ARBs in patients with diabetes is contraindicated. Combined use in other patients should be avoided, particularly when CrCl is less than 60 mL/min. If combined, monitor potassium, creatinine, and blood pressure closely. Risk D: Consider therapy modification

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Risk D: Consider therapy modification

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Angiotensin II: Receptor Blockers may diminish the therapeutic effect of Angiotensin II. Risk C: Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: Angiotensin II Receptor Blockers may enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Angiotensin II Receptor Blockers may increase the serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: In US labeling, use of telmisartan and ramipril is not recommended. It is not clear if any other combination of an ACE inhibitor and an ARB would be any safer. Consider alternatives to the combination when possible. Risk D: Consider therapy modification

Antihepaciviral Combination Products: May increase the serum concentration of Candesartan. Management: Per antihepaciviral combination product US prescribing information, consider decreasing the candesartan dose and monitoring for evidence of hypotension and worsening renal function if these agents are used in combination. Risk D: Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Risk X: Avoid combination

CycloSPORINE (Systemic): Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of CycloSPORINE (Systemic). Risk C: Monitor therapy

Dapoxetine: May enhance the orthostatic hypotensive effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Drospirenone: Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of Drospirenone. Risk C: Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

Eplerenone: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Heparin: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Heparins (Low Molecular Weight): May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy

Lithium: Angiotensin II Receptor Blockers may increase the serum concentration of Lithium. Management: Lithium dosage reductions will likely be needed following the addition of an angiotensin II receptor antagonist. Risk D: Consider therapy modification

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: Angiotensin II Receptor Blockers may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Potassium Salts: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Potassium-Sparing Diuretics: Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Ranolazine: May enhance the adverse/toxic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Sodium Phosphates: Angiotensin II Receptor Blockers may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with ARBs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely. Risk D: Consider therapy modification

Tacrolimus (Systemic): Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of Tacrolimus (Systemic). Risk C: Monitor therapy

Tolvaptan: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Trimethoprim: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Test Interactions

May lead to false-negative aldosterone/renin ratio (ARR) (Funder 2016).

Genes of Interest

Monitoring Parameters

Supine BP, electrolytes, serum creatinine, BUN, urinalysis, symptomatic hypotension, and tachycardia; in heart failure, serum potassium during dose escalation and periodically thereafter.

Heart Failure: Within 1 to 2 weeks after initiation, reassess BP (including postural blood pressure changes), renal function, and serum potassium; follow closely after dose changes. Patients with systolic BP <80 mm Hg, low serum sodium, diabetes mellitus, and impaired renal function should be closely monitored (ACC/AHA [Yancy 2013]).

Hypertension: The 2017 guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults (ACC/AHA [Whelton 2018]):

Confirmed hypertension and known CVD or 10-year atherosclerotic cardiovascular disease risk ≥10%: Target BP <130/80 mm Hg is recommended.

Confirmed hypertension without markers of increased atherosclerotic cardiovascular disease risk: Target BP <130/80 mm Hg may be reasonable.

Diabetes and hypertension: The American Diabetes Association guidelines (ADA 2020):

Patients 18 to 65 years of age, without atherosclerotic cardiovascular disease, and 10-year atherosclerotic cardiovascular disease risk <15%: Target BP <140/90 mm Hg is recommended.

Patients 18 to 65 years of age and known atherosclerotic cardiovascular disease or 10-year atherosclerotic cardiovascular disease risk ≥15%: Target BP <130/80 mm Hg may be appropriate if it can be safely attained.

Patients >65 years of age (healthy or complex/intermediate health): Target BP <140/90 mm Hg is recommended.

Patients >65 years of age (very complex/poor health): Target BP <150/90 mm Hg is recommended.

Advanced Practitioners Physical Assessment/Monitoring

Obtain electrolytes, renal function, and urinalysis. Monitor blood pressure. Assess other medicines patient may be taking; alternate therapy or dosage adjustments may be needed. Monitor for tachycardia, CNS changes, hyperglycemia, and hypotension prior to treatment, when changing dose, and throughout therapy. Assess for signs of angioedema.

Nursing Physical Assessment/Monitoring

Check ordered labs and report abnormalities. Monitor blood pressure. Monitor for signs of tachycardia, CNS changes, hyperglycemia, and hypotension. Monitor for signs of angioedema.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral, as cilexetil:

Atacand: 4 mg [DSC] [scored]

Atacand: 4 mg [scored; contains corn starch]

Atacand: 8 mg [DSC] [scored]

Atacand: 8 mg [scored; contains corn starch]

Atacand: 16 mg [DSC] [scored]

Atacand: 16 mg [scored; contains corn starch]

Atacand: 32 mg [DSC] [scored]

Atacand: 32 mg [scored; contains corn starch]

Generic: 4 mg, 8 mg, 16 mg, 32 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as cilexetil:

Atacand: 4 mg, 8 mg, 16 mg, 32 mg

Generic: 4 mg, 8 mg, 16 mg, 32 mg

Anatomic Therapeutic Chemical (ATC) Classification

C09CA06

Generic Available (US)

Yes

Pricing: US

Tablets (Atacand Oral)

4 mg (per each): $7.33

8 mg (per each): $8.76

16 mg (per each): $9.42

32 mg (per each): $11.92

Tablets (Candesartan Cilexetil Oral)

4 mg (per each): $3.06 - $3.31

8 mg (per each): $3.06 - $3.31

16 mg (per each): $2.76 - $3.31

32 mg (per each): $4.17 - $4.47

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Candesartan is an angiotensin receptor antagonist. Angiotensin II acts as a vasoconstrictor. In addition to causing direct vasoconstriction, angiotensin II also stimulates the release of aldosterone. Once aldosterone is released, sodium as well as water are reabsorbed. The end result is an elevation in blood pressure. Candesartan binds to the AT1 angiotensin II receptor. This binding prevents angiotensin II from binding to the receptor thereby blocking the vasoconstriction and the aldosterone secreting effects of angiotensin II.

Pharmacodynamics/Kinetics

Onset of action: 2 to 3 hours; antihypertensive effect: Within 2 weeks

Peak effect: 6 to 8 hours; maximum antihypertensive effect: 4 to 6 weeks

Duration: >24 hours

Absorption: Candesartan: Rapid and complete following conversion from candesartan cilexetil by GI esterases

Distribution: V_d: 0.13 L/kg

Protein binding: >99%

Metabolism: Converted to active candesartan, via ester hydrolysis during absorption from GI tract; hepatic (minor) via O-deethylation to inactive metabolite

Bioavailability, absolute: Candesartan: 15%

Half-life elimination (dose dependent): 5 to 9 hours

Time to peak: Children (1 to 17 years); Adults: 3 to 4 hours

Excretion: Feces (67%); urine (33%; 26% as unchanged drug)

Clearance: Total body: 0.37 mL/minute/kg; Renal: 0.19 mL/minute/kg; decreased with severe renal impairment

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: In hypertensive patients with CrCl <30 mL/minute/1.73 m², the AUC and C_max are approximately doubled. In heart failure patients with renal impairment, AUC is 36% and 65% higher and C_max is 15% and 55% higher in patients with mild and moderate renal impairment, respectively.

Hepatic function impairment: The AUC and C_max increased 30% and 56% in mild impairment and 145% and 73% in moderate impairment, respectively.

Geriatric: C_max is ~50% higher; AUC is ~80% higher.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Patients may experience orthostatic hypotension as they stand up after treatment; especially if lying in dental chair for extended periods of time. Use caution with sudden changes in position during and after dental treatment.

Effects on Bleeding

No information available to require special precautions

Related Information

Pharmacotherapy Pearls

May have an advantage over losartan due to minimal metabolism requirements and consequent use in mild-to-moderate hepatic impairment

Index Terms

Candesartan Cilexetil

FDA Approval Date

June 04, 1998

References

Alwan S, Polifka JE, Friedman JM. Angiotensin II receptor antagonist treatment during pregnancy. Birth Defects Res A Clin Mol Teratol. 2005;73(2):123-130.

American College of Obstetricians and Gynecologists (ACOG). ACOG Practice Bulletin No. 203: Chronic hypertension in pregnancy. Obstet Gynecol. 2019;133(1):e26-e50. doi: 10.1097/AOG.0000000000003020.[PubMed 30575676]

American Diabetes Association (ADA). Standards of medical care in diabetes–2020. Diabetes Care. 2020;43(suppl 1):S1-S212. https://care.diabetesjournals.org/content/43/Supplement_1. Accessed January 22, 2020.

Amsterdam EA, Wenger NK, Brindis RG, et al; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons; American Association for Clinical Chemistry. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [published correction appears in J Am Coll Cardiol. 2014;64(24):2713-2714]. J Am Coll Cardiol. 2014;64(24):e139-e228. doi: 10.1016/j.jacc.2014.09.017.[PubMed 25260718]

Anderson PO, Sauberan JB. Modeling drug passage into human milk. Clin Pharmacol Ther. 2016;100(1):42-52.[PubMed 27060684]

Atacand (candesartan) [prescribing information]. Wilmington, DE: AstraZeneca LP; May 2018.

Atacand (candesartan) [product monograph]. Mississauga, Ontario, Canada: AstraZeneca Canada Inc; February 2016.

Bakris GL. Treatment of diabetic nephropathy. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 11, 2019.

Beltrami L, Zanichelli A, Zingale L, Vacchini R, Carugo S, Cicardi M. Long-term follow-up of 111 patients with angiotensin-converting enzyme inhibitor-related angioedema. J Hypertens. 2011;29(11):2273-2277. doi: 10.1097/HJH.0b013e32834b4b9b.[PubMed 21970934]

Cabiddu G, Castellino S, Gernone G, et al. A best practice position statement on pregnancy in chronic kidney disease: the Italian Study Group on Kidney and Pregnancy. J Nephrol. 2016;29(3):277-303.[PubMed 26988973]

Cattran DC, Appel GB. Treatment and prognosis of IgA nephropathy. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 16, 2019.

Coberger ED, Jensen BP, Dalrymple JM. Transfer of candesartan into human breast milk. Obstet Gynecol. 2019;134(3):481-484.[PubMed 31403599]

Fleisher LA, Fleischmann KE, Auerbach AD, et al. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130(24):2215-2245. doi: 10.1161/CIR.0000000000000105.[PubMed 25085962]

Franks AM, O'Brien CE, Stowe CD, et al. Candesartan cilexetil effectively reduces blood pressure in hypertensive children. Ann Pharmacother. 2008;42(10):1388-1395.[PubMed 18664605]

Funder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916. doi: 10.1210/jc.2015-4061.[PubMed 26934393]

Granger CB, McMurray JJ, Yusuf S, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-alternative trial. Lancet. 2003;362(9386):772-776.[PubMed 13678870]

Guyer AC, Banerji A. ACE inhibitor-induced angioedema. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 26, 2019.

Hillis LD, Smith PK, Anderson JL, et al. 2011 ACCF/AHA guideline for coronary artery bypass graft surgery: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011;124(23):2610-2642.[PubMed 22064600]

Hoy SM, Keating GM. Candesartan cilexetil: in children and adolescents aged 1 to <17 years with hypertension. Am J Cardiovasc Drugs. 2010;10(5):335-342.[PubMed 20860416]

Ito S. Drug therapy for breast-feeding women. N Engl J Med. 2000;343(2):118-126.[PubMed 10891521]

January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 2014;130(23):2071-2104.[PubMed 24682348]

Kidney Disease: Improving Global Outcomes (KDIGO). Chapter 10: Immunoglobulin A nephropathy. Kidney Int Suppl (2011). 2012;2(2):209-217.[PubMed 25018935]

Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl (2013). 2013;3(1):1-150. https://kdigo.org/wp-content/uploads/2017/02/KDIGO_2012_CKD_GL.pdf.

Mann JFE. Choice of drug therapy in primary (essential) hypertension. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 16, 2019a.

Mann JFE, Bakris GL. Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 16, 2019b.

McCulloch DK, Bakris GL. Moderately increased albuminuria (microalbuminuria) in type 1 diabetes mellitus. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 12, 2019.

Meyer TE. Initial pharmacologic therapy of heart failure with reduced ejection fraction in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 24, 2019.

Nishimura RA, Otto CM, Bonow RO, et al, 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(23):2440-92. doi: 10.1161/CIR.0000000000000029.[PubMed 24589852]

O'Gara PT, Kushner FG, Ascheim DD, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines [published correction appears in Circulation. 2013;128(25):e481]. Circulation. 2013;127(4):e362-e425. doi: 10.1161/CIR.0b013e3182742cf6.[PubMed 23247304]

Pfeffer MA, Swedberg K, Granger CB, et al; CHARM Investigators and Committees. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme [published correction appears in Lancet. 2009;(9703):1744]. Lancet. 2003;362(9386):759-766. doi: 10.1016/s0140-6736(03)14282-1.[PubMed 13678868]

Porta M, Hainer JW, Jansson SO, et al. Exposure to candesartan during the first trimester of pregnancy in type 1 diabetes: experience from the placebo-controlled DIabetic REtinopathy Candesartan Trials. Diabetologia. 2011;54(6):1298-1303.[PubMed 21225239]

Rasmussen ER, Pottegård A, Bygum A, von Buchwald C, Homøe P, Hallas J. Angiotensin II receptor blockers are safe in patients with prior angioedema related to angiotensin-converting enzyme inhibitors – a nationwide registry-based cohort study. J Intern Med. 2019;285(5):553-561. doi: 10.1111/joim.12867.[PubMed 30618189]

Rosendorff C, Lackland DT, Allison M, et al; American Heart Association, American College of Cardiology, and American Society of Hypertension. Treatment of hypertension in patients with coronary artery disease: A scientific statement from the American Heart Association, American College of Cardiology, and American Society of Hypertension. J Am Soc Hypertens. 2015;9(6):453-498. doi: 10.1016/j.jash.2015.03.002.[PubMed 25840695]

Runyon BA; American Association for the Study of Liver Diseases. Practice guideline: management of adult patients with ascites due to cirrhosis: update 2012. http://aasld.org/sites/default/files/guideline_documents/adultascitesenhanced.pdf. Accessed March 2, 2019.[PubMed 23463403]

Schaefer F, van de Walle J, Zurowska A, et al. Efficacy, safety and pharmacokinetics of candesartan cilexetil in hypertensive children from 1 to less than 6 years of age. J Hypertens. 2010;28(5):1083-1090.[PubMed 20160654]

Sipahi I, Debanne SM, Rowland DY, et al. Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. Lancet Oncol. 2010;11(7):627-636.[PubMed 20542468]

Smith SC Jr, Benjamin EJ, Bonow RO, et al. AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation. 2011;124(22):2458-2473.[PubMed 22052934]

Toh S, Reichman ME, Houstoun M, et al. Comparative risk for angioedema associated with the use of drugs that target the renin-angiotensin-aldosterone system [published correction appears in Arch Intern Med. 2013;173(1):14]. Arch Intern Med. 2012;172(20):1582-1589. doi: 10.1001/2013.jamainternmed.34.[PubMed 23147456]

Trachtman H, Hainer JW, Sugg J, et al. Efficacy, safety, and pharmacokinetics of candesartan cilexetil in hypertensive children aged 6 to 17 years. J Clin Hypertens (Greenwich). 2008;10(10):743-750.[PubMed 19090875]

Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hyperten (Greenwich). 2014;16(1):14-26.[PubMed 24341872]

Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018;138(17):e484-e594.[PubMed 30354654]

Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines and the Heart Failure Society of America. Circulation. 2017;136(6):e137-e161. doi: 10.1161/CIR.0000000000000509.[PubMed 28455343]

Yancy CW, Jessup M, Bozkurt B, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013;128(16):e240-e327.[PubMed 23741058]

Yusuf S, Pfeffer MA, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-preserved trial. Lancet. 2003;362(9386):777-781.[PubMed 13678871]

Brand Names: International

Advant (LK); Aldireca (NL); Amias (GB); Amican (HK); Anatan (KR); Arb (BD); Atacan (KR); Atacand (AE, AR, AT, AU, BB, BF, BG, BH, BJ, BM, BR, BS, BZ, CH, CI, CL, CO, CU, CY, CZ, DE, DK, EE, EG, ES, ET, FI, FR, GH, GM, GN, GR, HR, HU, IE, IL, IS, JM, JO, KE, KR, KW, LB, LK, LR, LT, LU, LV, MA, ML, MR, MT, MU, MW, MX, MY, NE, NG, NL, NO, NZ, PE, PL, PR, PT, QA, RO, RU, SA, SC, SD, SE, SG, SI, SK, SL, SN, TN, TR, TT, TZ, UA, UG, UY, ZA, ZM, ZW); Atasart (PH, VN); Bilaten (CL); Blopress (AE, AT, BB, BH, BM, BR, BS, BZ, CH, CN, CR, CY, DE, DO, EC, EG, ES, GT, GY, HK, HN, ID, IE, IQ, IR, IT, JM, JO, JP, KW, LB, LY, MX, MY, NI, NL, OM, PA, PE, PH, PK, PR, QA, SA, SG, SR, SV, SY, TH, TT, TW, VE, YE); Blox (CL); Blox 8 (PY); Candefar (ID); Candelong (LK); Candelotan (KR); Candepress (SA, TR); Canderin (ID); Candesar (EG, IN, KR, UA); Candesarkern (VN); Candiloc (BD); Candist (IE); Cansartan (KR); Cantar (IN, VN); Casartan (PH); Catasart (IE); Dacten (PY); Desaltan (KR); Finil 16 (TH); Frepan (PH); Giran (BD); Hysart (LK); Kairasec (NL); Kanda-16 (TH); Kandepres (HR); Kasark (UA); Kenzen (FR); Sartan (BD); Sartan-16 (PH); Sartan-8 (PH); Tenecand (VN); Tiadyl (AR); Todesaar (TH); Torcand-16 (PH); Torcand-8 (PH); Treatan (LK); Vanox (PY)

Last Updated 3/10/20

Google Sites

Report abuse