When pregnancy is detected, discontinue candesartan as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus.
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
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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.
Mild hepatic impairment: No initial dosage adjustment required.
Moderate hepatic impairment: There are no pediatric-specific dosage adjustments provided in the manufacturer's labeling.
Severe hepatic impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
(For additional information see "Candesartan: Drug information")
Acute coronary syndrome:
Note: May be used as an alternative in patients who cannot tolerate an angiotensin-converting enzyme (ACE) inhibitor (eg, due to cough or angioedema) (Ref). Angiotensin II receptor blockers (ARBs) do not appear to elevate the risk of angioedema (Ref); however, patients must be educated that angioedema due to an ACE inhibitor can sometimes reoccur within months following discontinuation (Ref); 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) (Ref). 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 (Ref). 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 (alternative agent):
Note: Alternative therapy in patients who cannot tolerate an angiotensin II receptor-neprilysin inhibitor (ARNI) or an ACE inhibitor (eg, due to cough or angioedema); consultation with a heart failure specialist and/or an allergist may be appropriate (Ref). ARBs do not appear to elevate the risk of angioedema (Ref); however, angioedema due to an ACE inhibitor can sometimes reoccur months following discontinuation (Ref).
Oral: Initial: 4 to 8 mg once daily; increase dose (eg, double) every ≥ 1 to 2 weeks based on response and tolerability to a target dose of 32 mg once daily (Ref). In hospitalized patients, may titrate more rapidly as tolerated (Ref).
Hypertension, chronic:
Note: For patients who warrant combination therapy (BP >20/10 mm Hg above goal or suboptimal response to initial monotherapy), may use with another appropriate agent (eg, long-acting dihydropyridine calcium channel blocker or thiazide diuretic) (Ref).
Oral: Initial: 8 mg once daily; evaluate response after approximately 2 to 4 weeks and titrate dose (eg, increase the daily dose by doubling), as needed, up to 32 mg once daily; if additional blood pressure control is needed, consider combination therapy. Patients with severe asymptomatic hypertension and no signs of acute end organ damage should be evaluated for medication titration within 1 week (Ref).
Migraine, prevention (alternative agent) (off-label use):
Note: Among second-line agents for migraine prevention, consider use in patients with comorbid hypertension (Ref). An adequate trial for assessment of effect is considered to be at least 2 to 3 months at a therapeutic dose (Ref).
Oral: Initial: 4 to 8 mg once daily; may increase dose (eg, by doubling) weekly based on response and tolerability up to 16 mg once daily (Ref).
Proteinuric chronic kidney disease, diabetic or nondiabetic (off-label use):
Oral: Initial: 8 mg once daily; titrate gradually (eg, by doubling the dose every 2 to 4 weeks) to the maximally tolerated dose, not to exceed 32 mg/day. If proteinuria target is not met despite optimized dosage, consider additional therapies (eg, sodium-glucose cotransporter-2 inhibitor) (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Kidney impairment prior to treatment initiation:
Altered kidney function:
CrCl >30 mL/minute/1.73 m2: No dosage adjustment necessary (Ref).
CrCl ≤30 mL/minute/1.73 m2: Start with a lower initial dose (eg, 4 mg once daily); titrate gradually based on tolerability and efficacy with frequent monitoring of BP, kidney function, and potassium (Ref). Maximum recommended dose: 16 mg once daily (Ref).
Hemodialysis, intermittent (thrice weekly): Not significantly dialyzed (Ref):
Start with a lower initial dose (eg, 4 mg once daily); titrate gradually based on tolerability and efficacy with frequent monitoring of BP, kidney function, and potassium (Ref). Maximum recommended dose: 16 mg once daily (Ref).
Peritoneal dialysis: Not likely to be significantly dialyzed (Ref):
Start with a lower initial dose (eg, 4 mg once daily); titrate gradually based on tolerability and efficacy with frequent monitoring of BP, kidney function, and potassium (Ref). Maximum recommended dose: 16 mg once daily (Ref).
CRRT: Start with lower initial dose (eg, 4 mg once daily) and titrate gradually based on tolerability and efficacy with frequent monitoring of BP, kidney function, and potassium. Maximum recommended dose: 16 mg once daily (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Start with lower initial dose (eg, 4 mg once daily) and titrate gradually based on tolerability and efficacy with frequent monitoring of BP, kidney function, and potassium. Maximum recommended dose: 16 mg once daily (Ref).
Alterations in kidney function during treatment:
Small, transient increases in serum creatinine are likely to occur within 4 weeks following initiation of therapy or an increase in dose. If serum creatinine increases by >30%, review for possible etiologies (eg, acute kidney injury, volume depletion, concomitant medications, renal artery stenosis) before determining if dose reduction or discontinuation of candesartan therapy should be considered (Ref).
Mild impairment (Child-Pugh class A): No initial dosage adjustment necessary.
Moderate impairment (Child-Pugh class B): Initial: 4 to 8 mg daily in patients with hypertension; titrate gradually based on tolerability and efficacy.
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. Should be used with caution in patients with ascites due to cirrhosis (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>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
Hypersensitivity to candesartan or any component of the formulation; concomitant use with aliskiren in patients with diabetes mellitus.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Concomitant use with aliskiren in patients with moderate to severe kidney impairment (GFR <60 mL/minute/1.73 m2); pregnancy; breastfeeding; children <1 year of age; rare hereditary problems of galactose intolerance, congenital lactase deficiency or glucose-galactose malabsorption.
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 kidney 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.
• Kidney function deterioration: May be associated with deterioration of kidney 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 kidney 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 kidney function.
Disease-related concerns:
• Aortic/mitral stenosis: Use caution in patients with significant aortic/mitral stenosis.
• Ascites: Generally, 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 kidney function carefully to avoid rapid development of kidney failure (AASLD [Biggins 2021]; AASLD [Runyon 2013]).
• Hepatic impairment: Systemic exposure increases in hepatic impairment; dosage adjustment may be necessary.
• Renal artery stenosis: Use candesartan with caution in patients with unstented unilateral/bilateral kidney artery stenosis. When unstented bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in kidney function unless possible benefits outweigh risks.
• Kidney impairment: Use with caution with preexisting kidney insufficiency. Pediatric patients with a GFR <30 mL/minute/1.73 m2 should not receive candesartan; has not been evaluated.
Special populations:
• Pediatric: Avoid use in infants <1 year of age due to potential effects on the development of immature kidneys.
• Race/Ethnicity: Some studies suggest that when used as monotherapy for hypertension, the BP-lowering effects of renin-angiotensin system (RAS) inhibitors (eg, angiotensin receptor blockers) may be somewhat less pronounced in Black patients (ACC/AHA [Whelton 2018]). The mechanism is not known but may be related to social determinants of health rather than race, as pharmacogenetic differences have not been found to adequately predict blood pressure response (Brewster 2013; Gardner 2022). These observed BP differences were not apparent when RAS inhibitors were used as part of combination therapy (eg, combined with a calcium channel blocker or thiazide diuretic) (Jamerson 2008). Drug selection should be individualized and based on multiple patient-specific factors and not purely race/ethnicity (Holt 2022).
• Surgical patients: In patients on chronic ARB therapy, intraoperative hypotension may occur with induction and maintenance of general anesthesia. Cardiopulmonary bypass, intraoperative blood loss, or vasodilating anesthesia increases endogenous renin release. Use of ARBs perioperatively will blunt angiotensin II effects and may result in hypotension; however, discontinuation of therapy prior to surgery is controversial. If continued preoperatively, avoidance of hypotensive agents during surgery is prudent (Hillis 2011). In patients undergoing elevated-risk noncardiac surgery who take an ARB for hypertension, it is reasonable to hold treatment 24 hours before surgery to limit intraoperative hypotension then restart postoperatively as soon as clinically feasible. In patients who take an ARB for heart failure, it is reasonable to continue therapy, uninterrupted, perioperatively (AHA/ACC [Thompson 2024]).
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 [scored; contains corn starch]
Generic: 4 mg, 8 mg, 16 mg, 32 mg
Yes
Tablets (Atacand Oral)
4 mg (per each): $7.70
8 mg (per each): $9.20
16 mg (per each): $9.89
32 mg (per each): $12.52
Tablets (Candesartan Cilexetil Oral)
4 mg (per each): $2.76 - $3.17
8 mg (per each): $2.76 - $3.17
16 mg (per each): $2.76 - $3.85
32 mg (per each): $4.17 - $5.39
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.
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
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).
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).
Oral: Administer without regard to meals. An oral suspension may be prepared for patients unable to swallow tablets (refer to Extemporaneously Prepared information).
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Treatment of hypertension alone or in combination with other antihypertensive agents (FDA approved in ages ≥1 year and adults); treatment of heart failure (NYHA class II-IV) (FDA approved in adults)
Atacand may be confused with antacid
Substrate of CYP2C9 (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Alfuzosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Aliskiren: May increase nephrotoxic effects of Angiotensin II Receptor Blockers. Aliskiren may increase hyperkalemic effects of Angiotensin II Receptor Blockers. Aliskiren may increase hypotensive effects 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 increase hypotensive effects of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider Therapy Modification
Amphetamines: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Angiotensin II: Angiotensin II Receptor Blockers may decrease therapeutic effects of Angiotensin II. Risk C: Monitor
Angiotensin-Converting Enzyme Inhibitors: Angiotensin II Receptor Blockers may increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Angiotensin II Receptor Blockers may increase serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: 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 when possible. Monitor blood pressure, renal function, and potassium if combined. Risk D: Consider Therapy Modification
Antihepaciviral Combination Products: May increase serum concentration of Candesartan. Management: 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 increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor
Arginine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Barbiturates: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Benperidol: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Brigatinib: May decrease antihypertensive effects of Antihypertensive Agents. Brigatinib may increase bradycardic effects of Antihypertensive Agents. Risk C: Monitor
Brimonidine (Topical): May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Bromperidol: May decrease hypotensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase hypotensive effects of Bromperidol. Risk X: Avoid
Dapoxetine: May increase orthostatic hypotensive effects of Angiotensin II Receptor Blockers. Risk C: Monitor
Dexmethylphenidate: May decrease therapeutic effects of Antihypertensive Agents. Risk C: Monitor
Diazoxide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Dipeptidyl Peptidase-IV Inhibitors: May increase adverse/toxic effects of Angiotensin II Receptor Blockers. Specifically, the risk for angioedema may be increased with this combination. Risk C: Monitor
Drospirenone-Containing Products: May increase hyperkalemic effects of Angiotensin II Receptor Blockers. Risk C: Monitor
DULoxetine: Blood Pressure Lowering Agents may increase hypotensive effects of DULoxetine. Risk C: Monitor
Finerenone: Angiotensin II Receptor Blockers may increase hyperkalemic effects of Finerenone. Risk C: Monitor
Flunarizine: May increase therapeutic effects of Antihypertensive Agents. Risk C: Monitor
Heparin: May increase hyperkalemic effects of Angiotensin II Receptor Blockers. Risk C: Monitor
Heparins (Low Molecular Weight): May increase hyperkalemic effects of Angiotensin II Receptor Blockers. Risk C: Monitor
Herbal Products with Blood Pressure Increasing Effects: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Herbal Products with Blood Pressure Lowering Effects: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Hypotension-Associated Agents: Blood Pressure Lowering Agents may increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Iloperidone: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Indoramin: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Isocarboxazid: May increase antihypertensive effects of Antihypertensive Agents. Risk X: Avoid
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may increase hypotensive effects of Levodopa-Foslevodopa. Risk C: Monitor
Lithium: Angiotensin II Receptor Blockers may increase serum concentration of Lithium. Management: Initiate lithium at lower doses in patients receiving an angiotensin II receptor blocker (ARB). Consider lithium dose reductions in patients stable on lithium therapy who are initiating an ARB. Monitor lithium concentrations closely when combined. Risk D: Consider Therapy Modification
Loop Diuretics: May increase hypotensive effects of Angiotensin II Receptor Blockers. Loop Diuretics may increase nephrotoxic effects of Angiotensin II Receptor Blockers. Risk C: Monitor
Lormetazepam: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Metergoline: May decrease antihypertensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase orthostatic hypotensive effects of Metergoline. Risk C: Monitor
Methylphenidate: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Molsidomine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Naftopidil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicergoline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicorandil: May increase hyperkalemic effects of Angiotensin II Receptor Blockers. Risk C: Monitor
Nicorandil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nitroprusside: Blood Pressure Lowering Agents may increase hypotensive effects of Nitroprusside. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (Topical): May decrease therapeutic effects of Angiotensin II Receptor Blockers. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents: May decrease therapeutic effects of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Angiotensin II Receptor Blockers may increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Risk C: Monitor
Obinutuzumab: May increase hypotensive effects 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 increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Perazine: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Pholcodine: Blood Pressure Lowering Agents may increase hypotensive effects of Pholcodine. Risk C: Monitor
Phosphodiesterase 5 Inhibitors: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Polyethylene Glycol-Electrolyte Solution: Angiotensin II Receptor Blockers may increase nephrotoxic effects of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor
Potassium Salts: May increase hyperkalemic effects of Angiotensin II Receptor Blockers. Risk C: Monitor
Potassium-Sparing Diuretics: May increase hyperkalemic effects of Angiotensin II Receptor Blockers. Risk C: Monitor
Prazosin: Antihypertensive Agents may increase hypotensive effects of Prazosin. Risk C: Monitor
Prostacyclin Analogues: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Quinagolide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Ranolazine: May increase adverse/toxic effects of Angiotensin II Receptor Blockers. Risk C: Monitor
Sacubitril: Angiotensin II Receptor Blockers may increase adverse/toxic effects of Sacubitril. Risk X: Avoid
Silodosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Sodium Phosphates: Angiotensin II Receptor Blockers may increase nephrotoxic effects of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor
Sparsentan: May increase adverse/toxic effects of Angiotensin II Receptor Blockers. Risk X: Avoid
Tacrolimus (Systemic): Angiotensin II Receptor Blockers may increase hyperkalemic effects of Tacrolimus (Systemic). Risk C: Monitor
Terazosin: Antihypertensive Agents may increase hypotensive effects of Terazosin. Risk C: Monitor
Tolvaptan: May increase hyperkalemic effects of Angiotensin II Receptor Blockers. Risk C: Monitor
Trimethoprim: May increase hyperkalemic effects of Angiotensin II Receptor Blockers. Risk C: Monitor
Urapidil: Antihypertensive Agents may increase hypotensive effects of Urapidil. Risk C: Monitor
Avoid use of an angiotensin II receptor blocker (ARB) in patients who may become pregnant and who are not using effective contraception (ADA 2022).
Medications considered acceptable for the treatment of chronic hypertension during pregnancy may generally be used in patients trying to conceive. ARBs are fetotoxic. Transition patients prior to conception to an agent preferred for use during pregnancy unless treatment with an ARB is absolutely necessary (ACC/AHA [Whelton 2018]; ACOG 2019; NICE 2019).
When candesartan is used for the treatment of proteinuric chronic kidney disease in patients who could become pregnant, discontinue use at the first positive pregnancy test (ADA 2022; Fakhouri 2023; Porta 2011).
Candesartan is effective for prevention of migraines. In general, preventive treatment for migraine in patients trying to become pregnant should be avoided. Options for patients planning a pregnancy should be considered as part of a shared decision-making process. Nonpharmacologic interventions should be considered initially. When needed, preventive treatment should be individualized considering the available safety data and needs of the patient should pregnancy occur. A gradual discontinuation of preventive medications is generally preferred when the decision is made to stop treatment prior to conception (ACOG 2022; AHS [Ailani 2021]).
Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Exposure to an angiotensin II receptor blocker (ARB) during the first trimester of pregnancy may be associated with an increased risk of fetal malformations (ACOG 2019; ESC [Regitz-Zagrosek 2018]). Following exposure during the second or third trimesters, drugs that act on the renin-angiotensin system are associated with oligohydramnios. Oligohydramnios, due to decreased fetal kidney function, may lead to fetal lung hypoplasia and skeletal malformations. Oligohydramnios may not appear until after an irreversible fetal injury has occurred. ARB use during pregnancy is also associated with anuria, hypotension, kidney failure, skull hypoplasia, and death in the fetus/neonate. Monitor infants exposed to an ARB in utero for hyperkalemia, hypotension, and oliguria. Exchange transfusions or dialysis may be required to reverse hypotension or improve renal function.
Chronic maternal hypertension is also associated with adverse events in the fetus/infant. Chronic maternal hypertension may increase the risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to the duration and severity of maternal hypertension. Untreated chronic hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, preeclampsia, delivery complications, stroke, and myocardial infarction (ACOG 2019).
Discontinue ARBs as soon as possible once pregnancy is detected. Agents other than an ARB are recommended for the treatment of chronic hypertension during pregnancy (ACOG 2019; ESC [Cífková 2020]; ESC [Regitz-Zagrosek 2018]; SOGC [Magee 2022]). Closely monitor patients exposed to an ARB during pregnancy with serial ultrasounds.
ARBs are not recommended for the treatment of proteinuric chronic kidney disease during pregnancy. When treatment is needed in patients with diabetic nephropathy, candesartan should be discontinued at the first positive pregnancy test (Fakhouri 2023; Porta 2011).
In general, preventive treatment for migraine should be avoided during pregnancy. Options for pregnant patients should be considered as part of a shared decision-making process. Nonpharmacologic interventions should be considered initially. When needed, preventive treatment should be individualized considering the available safety data, the potential for adverse maternal and fetal events, and needs of the patient (ACOG 2022; AHS [Ailani 2021]). Candesartan is not recommended for migraine prevention during pregnancy (ACOG 2022).
Blood pressure, serum creatinine, BUN, baseline and periodic serum electrolytes (particularly K), urinalysis
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.
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: Vd: 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 kidney impairment
Altered kidney function: In hypertensive patients with CrCl <30 mL/minute/1.73 m2, the AUC and Cmax are approximately doubled. In heart failure patients with kidney impairment, AUC is 36% and 65% higher and Cmax is 15% and 55% higher in patients with mild and moderate kidney impairment, respectively.
Hepatic function impairment: The AUC and Cmax increased 30% and 56% in mild impairment and 145% and 73% in moderate impairment, respectively.
Older adult: Cmax is ~50% higher; AUC is ~80% higher.