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 (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.
(For additional information see "Candesartan: Drug information")
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 or angioedema) (ACC/AHA [Amsterdam 2014; O'Gara 2013]; Guyer 2021). Angiotensin II receptor blockers (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 (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 (AHA/ACC/HFSA [Heidenreich 2022]; Guyer 2021; Meyer 2021). ARBs do not appear to elevate the risk of angioedema (Rasmussen 2019; Toh 2012); however, angioedema due to an ACE inhibitor can sometimes reoccur months following discontinuation (Beltrami 2011).
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 (AHA/ACC/HFSA [Heidenreich 2022]). In hospitalized patients, may titrate more rapidly as tolerated (Meyer 2021).
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) (ACC/AHA [Whelton 2018]).
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 (ACC/AHA [Whelton 2018]; Mann 2021).
Migraine, prevention (alternative agent) (off-label use):
Note: Among second-line agents for migraine prevention, consider use in patients with comorbid hypertension (CHS [Pringsheim 2012]). An adequate trial for assessment of effect is considered to be at least 2 to 3 months at a therapeutic dose (EHF [Steiner 2019]).
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 (Sánchez-Rodríguez 2021; Stovner 2014).
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; Bakris 2022; Mann 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 2019).
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 2022).
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 (Buter 1999; Easthope 2002).
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 (ACC/AHA [Yancy 2013]; expert opinion). Maximum recommended dose: 16 mg once daily (expert opinion).
Hemodialysis, intermittent (thrice weekly): Not significantly dialyzed (Pfister 1999):
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 (ACC/AHA [Yancy 2013]; Buter 1999; Pfister 1999; Schulz 2009; expert opinion). Maximum recommended dose: 16 mg once daily (Ottoson 2003).
Peritoneal dialysis: Not likely to be significantly dialyzed (expert opinion):
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 (ACC/AHA [Yancy 2013]; expert opinion). Maximum recommended dose: 16 mg once daily (expert opinion).
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 (expert opinion).
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 (expert opinion).
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 (KDIGO 2020).
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. Should be used with caution in patients with ascites due to cirrhosis (AASLD [Biggins 2021]; AASLD [Runyon 2013]).
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
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: 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 children 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
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.
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 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 [Runyon 2013]).
• 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 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.
• 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.
• Race/Ethnicity: In Black patients, the BP-lowering effects of ARBs may be less pronounced. The exact mechanism is not known; differences in the renin-angiotensin-aldosterone system, low renin levels, and salt sensitivity more commonly found in Black patients may contribute (Brewster 2013; Helmer 2018; manufacturer's labeling).
• 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]).
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 Lexicomp 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 Lexicomp drug interactions program
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 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 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: 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 the 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 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: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
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-Containing Products: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. 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
Finerenone: Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of Finerenone. Risk C: Monitor therapy
Flunarizine: May enhance the therapeutic effect of Antihypertensive Agents. 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
Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: 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: 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 enhance the hypotensive effect of Angiotensin II Receptor Blockers. Loop Diuretics may enhance the nephrotoxic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
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
Nonsteroidal Anti-Inflammatory Agents (Topical): May diminish the therapeutic effect of Angiotensin II Receptor Blockers. 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. Risk C: Monitor therapy
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
The use of angiotensin II receptor blockers should generally be avoided in females 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).
[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 kidney 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, kidney 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 patients who are pregnant (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).
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.
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).
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): $2.76 - $3.17
8 mg (per each): $2.76 - $3.17
16 mg (per each): $2.76 - $3.18
32 mg (per each): $4.17 - $4.30
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