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Candesartan and hydrochlorothiazide: Drug information

Candesartan and hydrochlorothiazide: Drug information
(For additional information see "Candesartan and hydrochlorothiazide: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Fetal toxicity:

When pregnancy is detected, discontinue use as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus.

Brand Names: US
  • Atacand HCT
Brand Names: Canada
  • ACCEL-Candesartan/HCTZ [DSC];
  • APO-Candesartan/HCTZ [DSC];
  • Atacand Plus;
  • Auro-Candesartan HCT;
  • JAMP Candesartan-HCT;
  • NRA-Candesartan HCTZ;
  • PMS-Candesartan HCTZ;
  • SANDOZ Candesartan Plus;
  • TEVA-Candesartan/HCTZ
Pharmacologic Category
  • Angiotensin II Receptor Blocker;
  • Antihypertensive;
  • Diuretic, Thiazide
Dosing: Adult
Hypertension

Hypertension:

Note: If a lower dose of either medication is necessary, prescribe individual components separately then titrate dose(s) as needed and convert to combination tablet when appropriate (Ref).

Oral: Initial: Candesartan 16 mg/hydrochlorothiazide 12.5 mg once daily; titrate as needed based on patient response after ~2 to 4 weeks of therapy; maximum dosage of combination product: Candesartan 32 mg/hydrochlorothiazide 25 mg per day.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute: No dosage adjustment provided in manufacturer's labeling (safety and efficacy not established); however, AUC and serum levels of candesartan are increased, and the half-life of hydrochlorothiazide is prolonged in severe impairment. Use is contraindicated in anuric patients.

Dosing: Hepatic Impairment: Adult

US labeling:

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

Moderate to severe impairment (Child-Pugh classes B and C): Not recommended for initiation since an appropriate adjusted dose is not commercially available.

Canadian labeling:

Mild to moderate impairment: Titrate individual components cautiously.

Severe impairment and/or cholestasis: Use is contraindicated.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reactions which follow have been reported with the combination product; see individual drug agents for additional adverse reactions that may be expected from each agent.

1% to 10%:

Central nervous system: Dizziness (3%), headache (3%, placebo 5%)

Neuromuscular & skeletal: Back pain (3%)

Respiratory: Upper respiratory tract infection (4%), flu-like symptoms (3%)

<1%: Abdominal pain, agranulocytosis, angina pectoris, angioedema (<0.5%), anxiety, arthralgia, arthritis, bradycardia, bronchitis, chest pain, conjunctivitis, cough, cystitis, depression, dermatitis, diaphoresis, diarrhea, dyspepsia, dyspnea, ECG abnormality, eczema, epistaxis, extrasystoles, fatigue, gastritis, gastroenteritis, hematuria, hepatic abnormality, hepatitis, hyperglycemia, hyperuricemia, hypoesthesia, hypokalemia, increased blood urea nitrogen, increased creatine phosphokinase, increased serum transaminases, increased susceptibility to infection, insomnia, leg cramps, leukopenia, myalgia, myocardial infarction (<0.5%), nausea, neutropenia, osteoarthritis, pain, palpitations, paresthesia, peripheral edema, pharyngitis, pruritus, rash, rhinitis, sciatica, sinusitis, tachycardia, tinnitus, urinary tract infection, urticaria, vertigo, viral infection, vomiting, weakness

Contraindications

Hypersensitivity to candesartan, hydrochlorothiazide or other sulfonamide-derived drugs, or any component of the formulation; anuria; 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.

Note: Although the FDA-approved product labeling states this medication is contraindicated in patients with hypersensitivity to sulfonamide-containing drugs, the scientific basis of this cross-sensitivity has been challenged. See “Warnings/Precautions” for more detail.

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); severe renal impairment (CrCl <30 mL/minute/1.73 m2); severe hepatic impairment and/or cholestasis; gout; hereditary problems of galactose intolerance, congenital lactase deficiency or glucose-galactose malabsorption; pregnancy; breastfeeding; infants <1 year of age

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 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.

• Electrolyte disturbances: Hyperkalemia may occur with ARBs; risk factors include renal dysfunction, diabetes mellitus, and 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. Thiazide diuretics may cause hypokalemia, hypochloremic alkalosis, hypomagnesemia, and hyponatremia.

• Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated by hydrochlorothiazide. This risk may be increased with doses ≥25 mg (Gurwitz 1997).

• Hypersensitivity reactions: Hypersensitivity reactions may occur with hydrochlorothiazide. Risk is increased in patients with a history of allergy or bronchial asthma.

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

• Kidney 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 glomerular filtration rate (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.

• Ocular effects: Hydrochlorothiazide may cause acute transient myopia and acute angle-closure glaucoma, typically occurring within hours to weeks following initiation; discontinue therapy immediately in patients with acute decreases in visual acuity or ocular pain. Additional treatments may be needed if uncontrolled intraocular pressure persists. Risk factors may include a history of sulfonamide or penicillin allergy.

• Photosensitivity: Photosensitization may occur.

• Skin cancer, nonmelanoma: Prolonged use (≥3 years) may increase the risk for squamous cell carcinoma up to 4 times and increase the risk for basal cell carcinoma up to 1.25 times compared to patients not treated with hydrochlorothiazide (Pedersen 2018; Pottegård 2017).

• Sulfonamide (“sulfa”) allergy: The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, two antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are less well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes.

Disease-related concerns:

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

• Ascites due to cirrhosis: Use with extreme caution or avoid hydrochlorothiazide in the management of ascites due to cirrhosis; may lead to rapid development of hyponatremia when used in combination with spironolactone and furosemide (AASLD [Runyon 2012]). Additionally, use of candesartan should generally be avoided in patients with ascites due to cirrhosis or refractory ascites; if use cannot be avoided in patients with ascites due to cirrhosis, monitor BP and kidney function carefully to avoid rapid development of kidney failure (AASLD [Biggins 2021]; AASLD [Runyon 2013]).

• Bariatric surgery: Dehydration: Avoid diuretics in the immediate postoperative period after bariatric surgery; electrolyte disturbances and dehydration may occur. Diuretics may be resumed, if indicated, once oral fluid intake goals are met (Ziegler 2009).

• Diabetes: Use hydrochlorothiazide with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control.

• Hepatic impairment: Systemic exposure of candesartan is increased in hepatic impairment. Not recommended for initiation in patients with moderate to severe hepatic impairment. In progressive or severe liver disease, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy/coma.

• Hypercalcemia: Thiazide diuretics may decrease renal calcium excretion; consider avoiding use in patients with hypercalcemia.

• Hypercholesterolemia: Use with caution in patients with moderate or high cholesterol concentrations; increased cholesterol and triglyceride levels have been reported with thiazides.

• Kidney impairment: Use candesartan with caution in patients with preexisting renal insufficiency. Cumulative effects may develop, including azotemia, in patients with impaired kidney function. Avoid hydrochlorothiazide in severe renal disease (ineffective). Use is contraindicated in anuric patients. The Canadian labeling also contraindicates use in patients with severe renal impairment (CrCl <30 mL/minute/1.73 m2).

• Parathyroid disease: Thiazide diuretics reduce calcium excretion; pathologic changes in the parathyroid glands with hypercalcemia and hypophosphatemia have been observed with prolonged use; should be discontinued prior to testing for parathyroid function.

• 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.

• Systemic lupus erythematosus (SLE): Hydrochlorothiazide can cause SLE exacerbation or activation.

Special populations:

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

• 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).

Dosage Forms: US

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

Tablet, Oral:

Atacand HCT: 32/25: Candesartan cilexetil 32 mg and hydrochlorothiazide 25 mg, 16/12.5: Candesartan cilexetil 16 mg and hydrochlorothiazide 12.5 mg, 32/12.5: Candesartan cilexetil 32 mg and hydrochlorothiazide 12.5 mg [scored; contains corn starch]

Generic: 16/12.5: Candesartan cilexetil 16 mg and hydrochlorothiazide 12.5 mg, 32/12.5: Candesartan cilexetil 32 mg and hydrochlorothiazide 12.5 mg, 32/25: Candesartan cilexetil 32 mg and hydrochlorothiazide 25 mg

Generic Equivalent Available: US

Yes

Pricing: US

Tablets (Atacand HCT Oral)

16-12.5 mg (per each): $10.83

32-12.5 mg (per each): $11.78

32-25 mg (per each): $13.36

Tablets (Candesartan Cilexetil-HCTZ Oral)

16-12.5 mg (per each): $4.72

32-12.5 mg (per each): $4.81

32-25 mg (per each): $5.21

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.

Dosage Forms: Canada

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

Tablet, Oral:

Atacand Plus: 32/25: Candesartan cilexetil 32 mg and hydrochlorothiazide 25 mg, 16/12.5: Candesartan cilexetil 16 mg and hydrochlorothiazide 12.5 mg, 32/12.5: Candesartan cilexetil 32 mg and hydrochlorothiazide 12.5 mg

Generic: 16/12.5: Candesartan cilexetil 16 mg and hydrochlorothiazide 12.5 mg, 32/12.5: Candesartan cilexetil 32 mg and hydrochlorothiazide 12.5 mg, 32/25: Candesartan cilexetil 32 mg and hydrochlorothiazide 25 mg

Administration: Adult

May administer with or without food.

Use: Labeled Indications

Hypertension: Management of hypertension.

Medication Safety Issues
Older Adult: High-Risk Medication:

Beers Criteria: Diuretics (hydrochlorothiazide) are identified in the Beers Criteria as potentially inappropriate medications to be used with caution in patients 65 years and older due to the potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium concentration closely when initiating or adjusting the dose in older adults (Beers Criteria [AGS 2023]).

Metabolism/Transport Effects

Refer to individual components.

Drug Interactions

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.

Ajmaline: Sulfonamides may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the orthostatic hypotensive effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

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

Allopurinol: Thiazide and Thiazide-Like Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk C: Monitor therapy

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

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy

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

Anticholinergic Agents: May increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Antidiabetic Agents: Thiazide and Thiazide-Like Diuretics may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

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

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

Arsenic Trioxide: Thiazide and Thiazide-Like Diuretics may enhance the hypotensive effect of Arsenic Trioxide. Thiazide and Thiazide-Like Diuretics may enhance the QTc-prolonging effect of Arsenic Trioxide. Management: When possible, avoid concurrent use of arsenic trioxide with drugs that can cause electrolyte abnormalities, such as the thiazide and thiazide-like diuretics. Risk D: Consider therapy modification

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

Beta2-Agonists: May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Thiazide and Thiazide-Like Diuretics. The diuretic response is likewise decreased. Management: Consider separating administraton of bile acid sequestrants and thiazide diuretics by at least 4 hours. Monitor for decreased therapeutic effects of thiazide diuretics if coadministered with a bile acid sequestrant. Risk D: Consider therapy modification

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

Calcium Salts: Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Calcium Salts. Risk C: Monitor therapy

Cardiac Glycosides: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Cardiac Glycosides. Specifically, cardiac glycoside toxicity may be enhanced by the hypokalemic and hypomagnesemic effect of thiazide diuretics. Risk C: Monitor therapy

Corticosteroids (Systemic): May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

CycloPHOSphamide: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of CycloPHOSphamide. Specifically, granulocytopenia may be enhanced. Risk C: Monitor therapy

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

Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

Dexketoprofen: May enhance the adverse/toxic effect of Sulfonamides. Risk C: Monitor therapy

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

Diacerein: May enhance the therapeutic effect of Diuretics. Specifically, the risk for dehydration or hypokalemia may be increased. Risk C: Monitor therapy

Diazoxide: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Diazoxide. Risk C: Monitor therapy

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

Dichlorphenamide: Thiazide and Thiazide-Like Diuretics may enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy

Dofetilide: HydroCHLOROthiazide may enhance the QTc-prolonging effect of Dofetilide. HydroCHLOROthiazide may increase the serum concentration of Dofetilide. Risk X: Avoid combination

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

Indoramin: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Ipragliflozin: May enhance the adverse/toxic effect of Thiazide and Thiazide-Like Diuretics. Specifically, the risk for intravascular volume depletion may be increased. Risk C: Monitor therapy

Ivabradine: Thiazide and Thiazide-Like Diuretics may enhance the arrhythmogenic effect of Ivabradine. Risk C: Monitor therapy

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

Levosulpiride: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Levosulpiride. Risk X: Avoid combination

Licorice: May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Lithium: Thiazide and Thiazide-Like Diuretics may decrease the excretion of Lithium. Management: Reduce the lithium dose if coadministered with thiazide or thiazide-like diuretics. Monitor serum lithium levels during coadministration with thiazide and thiazide-like diuretics. Risk D: Consider therapy modification

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

Loop Diuretics: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy

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

Mecamylamine: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Mecamylamine. Management: Consider avoiding the use of mecamylamine and thiazide diuretics. If combined, mecamylamine prescribing information suggests reducing the mecamylamine dose by 50% in order to avoid excessive hypotension. Risk D: Consider therapy modification

Methenamine: Thiazide and Thiazide-Like Diuretics may diminish the therapeutic effect of Methenamine. Risk C: Monitor therapy

Methotrexate: HydroCHLOROthiazide may enhance the nephrotoxic effect of Methotrexate. Risk C: Monitor therapy

Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). 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

Multivitamins/Fluoride (with ADE): May enhance the hypercalcemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): Thiazide and Thiazide-Like Diuretics may enhance the hypercalcemic effect of Multivitamins/Minerals (with ADEK, Folate, Iron). Risk C: Monitor therapy

Multivitamins/Minerals (with AE, No Iron): Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Multivitamins/Minerals (with AE, No Iron). Specifically, thiazide diuretics may decrease the excretion of calcium, and continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor therapy

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

Neuromuscular-Blocking Agents (Nondepolarizing): Thiazide and Thiazide-Like Diuretics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). 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: Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide and Thiazide-Like Diuretics. 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

Nonsteroidal Anti-Inflammatory Agents (Topical): May diminish the therapeutic effect of Thiazide and Thiazide-Like Diuretics. 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

Opioid Agonists: May enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. Risk C: Monitor therapy

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

Polyethylene Glycol-Electrolyte Solution: Angiotensin II Receptor Blockers may enhance the nephrotoxic effect of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor therapy

Polyethylene Glycol-Electrolyte Solution: Diuretics may enhance the nephrotoxic effect of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor therapy

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. 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

Prazosin: Antihypertensive Agents may enhance the hypotensive effect of Prazosin. Risk C: Monitor therapy

Promazine: Thiazide and Thiazide-Like Diuretics may enhance the QTc-prolonging effect of Promazine. Risk X: Avoid combination

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

Reboxetine: May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hyponatremic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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

Sodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor therapy

Sparsentan: May enhance the adverse/toxic effect of Angiotensin II Receptor Blockers. Risk X: Avoid combination

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

Terazosin: Antihypertensive Agents may enhance the hypotensive effect of Terazosin. Risk C: Monitor therapy

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

Topiramate: Thiazide and Thiazide-Like Diuretics may enhance the hypokalemic effect of Topiramate. Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Topiramate. Risk C: Monitor therapy

Toremifene: Thiazide and Thiazide-Like Diuretics may enhance the hypercalcemic effect of Toremifene. Risk C: Monitor therapy

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

Urapidil: Antihypertensive Agents may enhance the hypotensive effect of Urapidil. Risk C: Monitor therapy

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy

Vitamin D Analogs: Thiazide and Thiazide-Like Diuretics may enhance the hypercalcemic effect of Vitamin D Analogs. Risk C: Monitor therapy

Food Interactions

See individual agents.

Pregnancy Considerations

[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. Also see individual agents for additional information.

Breastfeeding Considerations

It is not known if candesartan is excreted in breast milk. Thiazides are excreted in breast milk. Due to the potential for serious adverse reactions in the nursing infant, the US labeling recommends a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother. The Canadian labeling contraindicates use in nursing women. Also refer to individual agents.

Monitoring Parameters

BP, heart rate; serum electrolytes; BUN, creatinine.

Mechanism of Action

Candesartan: 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 and 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.

Hydrochlorothiazide: Inhibits sodium reabsorption in the distal tubules causing increased excretion of sodium and water as well as potassium and hydrogen ions

Pharmacokinetics (Adult Data Unless Noted)

See individual agents.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Atacand plus | Blopress plus;
  • (AR) Argentina: Atacand d | Dacten d | Tiadyl plus;
  • (AT) Austria: Atacand plus | Blopress plus | Candeblo plus | Candesarcomp | Candesart/HCT Krka | Candesart/HCT Pluspharma | Candesart/HCT Stada | Candesarta/HCT Ratiopharm | Candesarta/HCT Sandoz | Candesartan Hct G.L. | Candesartan/hct | Candesartan/HCT 1a Pharma | Candesartan/HCT Actavis;
  • (AU) Australia: Adesan hct | Apo candesartan hctz | Asartan hct | Atacand plus | Candesan combi | Candesartan combi aspen | Candesartan hct | Candesartan hct gh | Candesartan hctz an | Candesartan hctz ga | Candesartan hctz rbx | Cm candesartan hctz | NOUMED CANDESARTAN/HCT | Pharmacor candesartan hct | Stada candesartan hct;
  • (BE) Belgium: Atacand plus | Candesartan plus hct EG | Co Candesartan;
  • (BF) Burkina Faso: Aderan htz;
  • (BG) Bulgaria: Acrux Plus | Candecard h | Candesartan hct | Candesartan hct aurobindo | Candestar h | Cantab plus | Cardesart co | Carzap h | Cocandesargen | Karbicombi | Repido plus;
  • (BR) Brazil: Angiotensil hct | Atacand hct | Candecor hct | Candemed hct | Candesartana cilexetila + hct | Candesartana cilexetila + hidroclorotiazida | Candessa hct | Cansarcor hct | Venzer hct;
  • (CH) Switzerland: Atacand plus | Blopress plus | Candesartan hct actavis | Candesartan hct helvepharm | Candesartan Plus | Cansartan mepha plus | Co Candesartan | Co candesartan spirig | Pemzek Plus;
  • (CI) Côte d'Ivoire: Aderan htz | Candisar H;
  • (CL) Chile: Atacand plus | Bilaten-D | Blopress d | Blox d;
  • (CN) China: Candesartan cilexetil and hydrochlorothiazide;
  • (CO) Colombia: Atacand plus | Candemox | Candeprex h | Candesartan + hidroclorotiazida | Candesartan/hct | Europres d | Minart plus;
  • (CZ) Czech Republic: Atacand plus | Cancombino | Candesartan/hydrochlorothiazid aurovitas | Carzap hct | Xaleec Combi;
  • (DE) Germany: Atacand plus | Blopresid | Blopresid plus | Blopress plus | Cande Q comp | Candecor comp | Candesarplus AL | Candesartan / HCT axunio | Candesartan comp puren | Candesartan comp. | Candesartan comp. AbZ | Candesartan comp. aurobindo | Candesartan hct krka | Candesartan hexal comp | Candesartan Hormosan comp | Candesartan plus 1a pharma | Candesartan ratiopharm comp | Candesartan Zentiva comp | Candesartan/hct heumann | Candesartan/hct stada | Candesartancilexetil/HCT Mylan | Hytacand Plus | Ratacand plus;
  • (DK) Denmark: Ratacand zid;
  • (DO) Dominican Republic: Acerta 3 | Acrosar D | Adepra H | Aracure-h | Atacand plus | Blopress plus | Blox d | Calmex h | Candersil D | Candesar h | Candesartan 16 mg + hidroclorotiazida 12.5 mg | Candesartan h | Candevex plus | Capsartan H | Cardiosartan d | Cardres h | Coriarten d | Coriarten max | Coropres h | Corprexia D | Corprexia Max | Decora H | Eucand H | Inlosep H | Kerala h | Minart plus | Safebul hct | Sulartan H | Tensinex h | Xiletil D | Xiletil forte | Xiletil H;
  • (EC) Ecuador: Atacand plus | Candesartan + hctz mk | Candesartan/hidroclorotiazida | Minart plus;
  • (EE) Estonia: Atacand plus | Candesartan cilexetil/Hydrochlorothiazide Teva | Candesartan hct actavis | Canocombi | Carzan hct | Prescanden hct;
  • (EG) Egypt: Albustix D | Atacand plus | Blopress plus | Candalkan Plus | Candeblock d | Sarcozide;
  • (ES) Spain: Atacand plus | Blopress plus | Candesartan/hct ratiopharm | Candesartan/hct stada | Candesartan/hidroclorotiazida actavis | Candesartan/hidroclorotiazida almus | Candesartan/hidroclorotiazida apotex ag | Candesartan/hidroclorotiazida cinfa | Candesartan/hidroclorotiazida combix | Candesartan/hidroclorotiazida davurgama | Candesartan/hidroclorotiazida ratiopharm | Candesartan/hidroclorotiazida tarbis | Candesartan/hydroclorotiazida aurobindo | Karbicombi | Parapres plus;
  • (ET) Ethiopia: Atacand plus | Candesartan cilexetil + hydrochlorothiazide | Candesartan cilexetil and hydrochlorothiazide;
  • (FI) Finland: Atacand plus | Candemox comp | Candesartan/Hydrochlorothiazide Orion | Candesartan/hydrochlorthiazid actavis | Candesartan/hydroklortiazid Krka | Candestad Comp | Candexetil Comp | Serbeca;
  • (FR) France: Candesartan/hydrochlorothiazide actavis | Candesartan/Hydrochlorothiazide Arrow | Candesartan/hydrochlorothiazide biogaran | Candesartan/Hydrochlorothiazide EG | Candesartan/hydrochlorothiazide evolugen | Candesartan/hydrochlorothiazide KRKA | Candesartan/Hydrochlorothiazide Mylan | Candesartan/hydrochlorothiazide ranbaxy | Candesartan/Hydrochlorothiazide sandoz | Candesartan/Hydrochlorothiazide Teva | Candesartan/Hydrochlorothiazide Zentiva | Cokenzen | Hytacand;
  • (GR) Greece: Atacand plus | Candesartan+Hydrochlorothiazide | Candesartan+hydrochlorothiazide/mylan | Fyronexe plus;
  • (HK) Hong Kong: Blopress plus;
  • (HR) Croatia: Atacand plus | Kandepres plus;
  • (HU) Hungary: Atacand plus | Karbicombi;
  • (ID) Indonesia: Blopress plus;
  • (IE) Ireland: Atacand plus | Blopress plus | Candesartan Hydrochlorothiazide Actavis | Candesartan Hydrochlorothiazide krka | Candist Plus | Catasart Plus;
  • (IL) Israel: Atacand plus | Candor plus;
  • (IN) India: Candelong-h | Candesar h;
  • (IS) Iceland: Candpress comp;
  • (IT) Italy: Blopresid | Candesartan e idroclorotiazide alter | Candesartan e idroclorotiazide eg | Candesartan e idroclorotiazide mylan | Candesartan e idroclorotiazide sandoz | Candesartan e idroclorotiazide teva | Candesartan e idroclorotiazide zentiva | Candesartan/ Idroclorotiazide Doc | Idrotens | Karbicombi | Ratacand plus;
  • (JO) Jordan: Atacand plus | Blopress plus | Coronasart plus | Gardia plus;
  • (JP) Japan: Cadethia | Ecard | Ecard hd | Ecard LD;
  • (KE) Kenya: Advantec | Atacand plus | Candecard hct | Gardia plus | Sarcozide;
  • (KR) Korea, Republic of: Anatan Plus | Atacand plus | Brcandaplus | Cabadil plus | Cancetil plus | Candante plus | Candecan plus | Candelotan Plus | Candemore Plus | Candeplus | Candera plus | Candesa plus | Candesan plus | Candesar Plus | Candeta plus | Candetan plus | Candro Plus | Cansartan Plus | Cansata Plus | Cantacan plus | Cantanplus | Cantaplus | Canzatan plus | Cowitacan | Desartan plus | Gloata Plus | Hisartan plus | Huniz canderplus | Hutecan plus | Kdc candesartan plus | Neocande plus;
  • (KW) Kuwait: Atacand plus | Blopress plus;
  • (LB) Lebanon: Atacand plus | Blopress plus | Candesartan/hydrochlorothiazide biogaran | Kronik plus | Pms candesart hctz;
  • (LT) Lithuania: Atacand plus | Candesartan hct actavis | Candesartan hct bijon | Canocombi | Carzan hct | Serbeca;
  • (LU) Luxembourg: Atacand plus | Candesartan ratiopharm comp | Co Candesartan;
  • (LV) Latvia: Atacand plus | Candesartan/HCT Actavis | Candesartan/hct teva | Canocombi;
  • (MX) Mexico: Aramistan | Atacand plus | Blopress plus | Candesartan/hidroclorotiazida sandoz | Coriatros duo | Safebul.hid;
  • (MY) Malaysia: Atacand plus | Candesartan hct sandoz;
  • (NG) Nigeria: Advantec | Atacand plus;
  • (NL) Netherlands: Atacand plus | Blopresid | Candesartan cilexetil / hct centrafarm | Candesartan cilexetil HCTZ Focus | Candesartan cilexetil hctz krka | Candesartan cilexetil/hydrochloorthiazide | Candesartan cilexetil/Hydrochloorthiazide Myl | Candesartan cilexetil/hydrochloorthiazide pch | Candesartan hct actavis | Candesartan/hct ratiopharm | Candesartancilexetil/HCTZ | Candesartancilexetil/Hydrochloorthiazide Sand | Silardaf hct;
  • (NO) Norway: Atacand plus | Atacand plus mite | Candemox comp | Candesartan Hydrochlorothiazide krka | Candesartan/hydrochlorothiazide aspen | Candesartan/hydrochlorothiazide KRKA | Candesartan/Hydrochlorothiazide Orion | Hytacand;
  • (PE) Peru: Atacand plus | Blopress plus | Blox d | Midopress plus;
  • (PH) Philippines: Blopress plus | Candez Plus | Sartan-h;
  • (PK) Pakistan: Advantec | Candesar h | Canrec plus | Cansaar Plus | Cansart plus | Carac H | Cartex H | Cazila | Prosartan Du | Sedanta z | Treatan D;
  • (PL) Poland: Candepres hct | Candesartan + Hydrochlorothiazide Vitama | Carzap hct | Karbicombi;
  • (PR) Puerto Rico: Atacand hct | Candesartan cilexetil and hydrochlorothiazide | Candesartan cilexetil and hydrochlorthiazide | Candesartan cilexetil-hydrochlorothiazide;
  • (PT) Portugal: Blopress 16/12.5mg | Candesartan + hidroclorotiazida actavis | Candesartan + Hidroclorotiazida Alter | Candesartan + Hidroclorotiazida Aurobindo | Candesartan + hidroclorotiazida azevedos | Candesartan + hidroclorotiazida bluepharma | Candesartan + Hidroclorotiazida Carpesir | Candesartan + hidroclorotiazida ciclum | Candesartan + hidroclorotiazida cinfa | Candesartan + hidroclorotiazida farmoz | Candesartan + hidroclorotiazida generis | Candesartan + hidroclorotiazida krka | Candesartan + hidroclorotiazida labesfal | Candesartan + Hidroclorotiazida Osir | Candesartan + hidroclorotiazida pharmakern | Candesartan + hidroclorotiazida ratiopharm | Candesartan + Hidroclorotiazida Sandoz | Candesartan + Hidroclorotiazida TAD | Candesartan + Hidroclorotiazida teva | Candesartan + hidroclorotiazida zentiva | Hytacand;
  • (PY) Paraguay: Atacand d | Blox d | Coropres h | Dacten d | Eticard d | Prexin d;
  • (QA) Qatar: Atacand Plus | Blopress Plus;
  • (RO) Romania: Candesartan hct swyssi | Candesartan hidroclorotiazida | Canzeno hct | Karbicombi;
  • (RU) Russian Federation: Atacand plus | Candecor N 16 | Candecor n 32 | Candecor n 8 | Candecor nd 32 | Ordiss h;
  • (SA) Saudi Arabia: Atacand plus | Blopress plus | Candan plus | Candeza plus | Codiceran | Gardia plus;
  • (SE) Sweden: Atacand plus | Blopress comp | Candemox comp | Candesarstad comp | Candesartan/Hydrochlorothiazide 2care4 | Candesartan/hydrochlorothiazide actavis | Candesartan/hydrochlorothiazide bijon | Candesartan/hydrochlorothiazide KRKA | Candesartan/Hydrochlorothiazide Orion | Candesartan/hydrochlorothiazide stada | Candesartan/Hydrochlorothiazide Teva | Candexetil Comp | Etilbo | Parapres comp forte;
  • (SG) Singapore: Atacand plus | Candesartan hct sandoz;
  • (SI) Slovenia: Atacand plus | Candea hct;
  • (SK) Slovakia: Atacand plus | Candemyl Combi | Candesartan hct | Candesartan hct actavis | Candesartan hct swyssi | Carzap hct | Karbicombi | Stadacand Plus;
  • (TH) Thailand: Blopress plus;
  • (TN) Tunisia: Aralead plus | Blopress plus | Etiken | Hytacand;
  • (TR) Turkey: Atacand plus | Ayra plus | Candecard Plus | Candexil Plus | Cantab plus | Co ucand | Tensart Plus;
  • (UA) Ukraine: Atacand plus | Casark h | Casark hd;
  • (UG) Uganda: Atacand plus | Sarcozide;
  • (UY) Uruguay: Blopress plus | Cancor D | Diapresan D;
  • (VE) Venezuela, Bolivarian Republic of: Atacand plus | Blocax plus | Blopress plus | Cander hct | Coropres h;
  • (ZA) South Africa: Atacand plus | Candepres plus | Mylacand plus | Ranepres plus;
  • (ZW) Zimbabwe: Atacand plus
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