Candesartan cilexetil/Hydrochlorothiazide

Description

Candesartan cilexetil and hydrochlorothiazide tablets combine an angiotensin II receptor (type AT1) antagonist, candesartan cilexetil, and the diuretic hydrochlorothiazide. Candesartan cilexetil is a nonpeptide compound with the chemical description of (±)-1-Hydroxyethyl 2-ethoxy-1-p-(o-1H-tetrazol-5-ylphenyl)benzyl-7-benzimidazolecarboxylate, cyclohexyl carbonate (ester). It has an empirical formula of C33H34N6O6, a molecular weight of 610.67, and appears as a white to off-white powder. Candesartan cilexetil is practically insoluble in water and sparingly soluble in methanol, existing as a racemic mixture with one chiral center at the cyclohexyloxycarbonyloxy ethyl ester group. Upon oral administration, it undergoes hydrolysis at the ester link to yield the active drug, candesartan, which is achiral.

Hydrochlorothiazide is chemically defined as 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide, with an empirical formula of C7H8ClN3O4S2 and a molecular weight of 297.72. It is a white or practically white crystalline powder, slightly soluble in water and freely soluble in sodium hydroxide solution.

Candesartan cilexetil and hydrochlorothiazide tablets, USP, are formulated for oral administration and are available in three strengths: 16 mg/12.5 mg, 32 mg/12.5 mg, and 32 mg/25 mg. The 16 mg/12.5 mg tablets contain 16 mg of candesartan cilexetil and 12.5 mg of hydrochlorothiazide, while the 32 mg/12.5 mg tablets contain 32 mg of candesartan cilexetil and 12.5 mg of hydrochlorothiazide. The 32 mg/25 mg tablets contain 32 mg of candesartan cilexetil and 25 mg of hydrochlorothiazide. Inactive ingredients include carboxymethylcellulose calcium, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate, corn starch, polyethylene glycol 6000, and microcrystalline cellulose. The 32 mg/12.5 mg tablets also contain ferric oxide (yellow) as a colorant.

Uses and Indications

Candesartan cilexetil and hydrochlorothiazide tablets are indicated for the treatment of hypertension to lower blood pressure. Effective management of hypertension is essential for reducing the risk of both fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions.

Control of high blood pressure should be integrated into a comprehensive cardiovascular risk management strategy, which includes lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. It is recognized that many patients may require a combination of antihypertensive medications to achieve their blood pressure goals.

Numerous antihypertensive agents have demonstrated efficacy in randomized controlled trials, showing a reduction in cardiovascular morbidity and mortality. The most significant cardiovascular outcome benefit observed is a reduction in the risk of stroke, alongside reductions in myocardial infarction and overall cardiovascular mortality. Elevated systolic or diastolic blood pressure is associated with increased cardiovascular risk, with a greater absolute risk increase per mmHg at higher blood pressures. Even modest reductions in severe hypertension can yield substantial health benefits.

The relative risk reduction associated with blood pressure lowering is consistent across diverse populations with varying absolute risk levels. Patients identified as being at higher risk, independent of their hypertension status—such as those with diabetes or hyperlipidemia—may benefit from more aggressive treatment aimed at achieving lower blood pressure targets. It is important to note that some antihypertensive medications may exhibit smaller blood pressure-lowering effects when used as monotherapy in black patients. Additionally, many antihypertensive drugs possess additional approved indications and effects, including those related to angina, heart failure, or diabetic kidney disease.

Dosage and Administration

The usual recommended starting dose of candesartan cilexetil is 16 mg administered once daily for patients who are not volume depleted and are receiving it as monotherapy. The dosing regimen may be adjusted to either once or twice daily, with total daily doses ranging from 8 mg to 32 mg. For patients requiring further reduction in blood pressure, titration to 32 mg is advised, as doses exceeding 32 mg do not demonstrate an increased efficacy in lowering blood pressure.

Hydrochlorothiazide can be effectively administered in doses ranging from 12.5 mg to 50 mg once daily. Candesartan cilexetil and hydrochlorothiazide tablets may be co-administered with other antihypertensive agents as needed. These tablets can be taken with or without food, providing flexibility in administration.

Contraindications

Candesartan cilexetil and hydrochlorothiazide tablets are contraindicated in patients with a known hypersensitivity to candesartan, hydrochlorothiazide, or other sulfonamide-derived drugs.

Co-administration of aliskiren with candesartan cilexetil and hydrochlorothiazide tablets is contraindicated in patients with diabetes due to the potential for adverse effects.

Additionally, these tablets are contraindicated in patients with anuria, as the lack of urine production may lead to complications associated with the pharmacological effects of the medication.

Warnings and Precautions

The use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy is associated with significant risks, including reduced fetal renal function and increased morbidity and mortality for both the fetus and neonate. Oligohydramnios resulting from such therapy can lead to fetal lung hypoplasia and skeletal deformations. Potential adverse effects in neonates may include skull hypoplasia, anuria, hypotension, renal failure, and death. Therefore, upon detection of pregnancy, it is imperative to discontinue candesartan cilexetil and hydrochlorothiazide tablets as soon as possible.

In cases where there is no suitable alternative to therapy with renin-angiotensin system-affecting drugs, healthcare providers must inform the mother of the potential risks to the fetus. Serial ultrasound examinations should be conducted to monitor the intra-amniotic environment. If oligohydramnios is detected, candesartan cilexetil and hydrochlorothiazide tablets should be discontinued unless deemed lifesaving for the mother. Fetal testing may be warranted depending on the gestational age. It is crucial to note that oligohydramnios may not manifest until after the fetus has sustained irreversible injury. Infants with a history of in utero exposure to these medications should be closely monitored for hypotension, oliguria, and hyperkalemia.

Candesartan cilexetil and hydrochlorothiazide tablets can induce symptomatic hypotension, particularly in patients who are volume and/or salt depleted due to prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting. Patients experiencing symptomatic hypotension may require a temporary reduction in the dosage of candesartan cilexetil and hydrochlorothiazide tablets or volume repletion. It is essential to correct any volume and/or salt depletion prior to initiating therapy with these tablets.

In patients with heart failure, the use of candesartan cilexetil and hydrochlorothiazide tablets may lead to excessive hypotension, which can result in oliguria, azotemia, and, in rare cases, acute renal failure and death. Therapy in these patients should commence under close medical supervision, with careful monitoring during the first two weeks of treatment and following any dose adjustments of candesartan or diuretics.

Renal function should be monitored periodically in patients receiving candesartan cilexetil and hydrochlorothiazide tablets, as changes in renal function, including acute renal failure, can occur due to the effects of drugs that inhibit the renin-angiotensin system and diuretics. Patients whose renal function may be influenced by the renin-angiotensin system are particularly at risk for developing oliguria, progressive azotemia, or acute renal failure. Consideration should be given to withholding or discontinuing therapy in patients who exhibit a clinically significant decline in renal function.

The use of drugs that inhibit the renin-angiotensin system can lead to hyperkalemia, while hydrochlorothiazide may cause hypokalemia and hyponatremia. Additionally, hypomagnesemia can result in treatment-resistant hypokalemia. Therefore, it is recommended to monitor serum electrolytes periodically.

Hydrochlorothiazide, classified as a sulfonamide, may provoke idiosyncratic reactions, including acute transient myopia and acute angle-closure glaucoma. Symptoms such as a sudden decrease in visual acuity or ocular pain may occur within hours to weeks of initiating treatment. If left untreated, acute angle-closure glaucoma can result in permanent vision loss. The primary course of action is to discontinue hydrochlorothiazide promptly, and if intraocular pressure remains uncontrolled, immediate medical or surgical intervention may be necessary.

Hypersensitivity reactions to hydrochlorothiazide can occur in patients with or without a prior history of allergy or bronchial asthma, although the likelihood is increased in those with such a history.

General precautions include the potential for hydrochlorothiazide to alter glucose tolerance and elevate serum cholesterol and triglyceride levels. Additionally, it may increase serum uric acid levels due to decreased clearance, potentially causing or exacerbating hyperuricemia and precipitating gout in susceptible individuals. Thiazides can also reduce urinary calcium excretion, leading to elevated serum calcium levels; therefore, the use of candesartan cilexetil and hydrochlorothiazide tablets is contraindicated in patients with hypercalcemia.

Regular monitoring of renal function and serum electrolytes is essential for patients treated with candesartan cilexetil and hydrochlorothiazide tablets to ensure safe and effective use of the medication.

Side Effects

Patients receiving treatment may experience a range of adverse reactions, which can be categorized by frequency and seriousness.

Common adverse reactions observed in clinical trials include respiratory system disorders such as upper respiratory tract infections, occurring in 3.6% of patients compared to 3.0% in the control group. Other notable common reactions include back pain (3.3% vs. 2.4%), influenza-like symptoms (2.5% vs. 1.9%), and dizziness (2.9% vs. 1.2%).

In addition to these common reactions, post-marketing experience has revealed several other adverse effects. Digestive system disorders may include abnormal hepatic function and hepatitis. Hematologic issues such as neutropenia, leukopenia, and agranulocytosis have also been reported. Immunologic reactions, including angioedema, have been noted, as well as metabolic and nutritional disorders like hyperkalemia and hyponatremia. Respiratory system disorders may manifest as cough, while skin and appendage disorders can include pruritus, rash, and urticaria. Rare cases of rhabdomyolysis have been documented in patients receiving angiotensin II receptor blockers.

Specific adverse reactions associated with hydrochlorothiazide include gastrointestinal disturbances such as pancreatitis, jaundice (intrahepatic cholestatic jaundice), sialadenitis, cramping, constipation, gastric irritation, and anorexia. Hematologic reactions may involve aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, and thrombocytopenia. Hypersensitivity reactions can range from anaphylactic reactions to necrotizing angiitis, respiratory distress (including pneumonitis and pulmonary edema), photosensitivity, urticaria, and purpura. Musculoskeletal effects may include muscle spasms, while skin reactions can involve erythema multiforme (including Stevens-Johnson syndrome), exfoliative dermatitis (including toxic epidermal necrolysis), and alopecia. Patients may also experience transient blurred vision and xanthopsia as special senses disorders, along with urogenital issues such as impotence.

Warnings associated with the use of these medications include potential fetal toxicity, particularly when drugs affecting the renin-angiotensin system are used during the second and third trimesters of pregnancy, which can lead to injury or death of the developing fetus. Symptomatic hypotension may occur, especially in patients who are volume and/or salt depleted. Changes in renal function, including acute renal failure, can also arise. Patients may experience potassium abnormalities, with hydrochlorothiazide potentially causing hypokalemia and hyponatremia. Additionally, hydrochlorothiazide may lead to acute myopia and secondary angle-closure glaucoma as an idiosyncratic reaction. Hypersensitivity reactions to hydrochlorothiazide can occur in patients with or without a prior history of allergy or bronchial asthma.

Metabolic disturbances associated with hydrochlorothiazide may include altered glucose tolerance, elevated serum levels of cholesterol and triglycerides, and increased serum uric acid levels, which may precipitate gout in susceptible individuals.

Drug Interactions

Candesartan, an angiotensin II receptor antagonist, exhibits a low potential for drug interactions due to its minimal metabolism by the cytochrome P450 system. Consequently, interactions with drugs that inhibit or are metabolized by these enzymes are not anticipated.

Pharmacodynamic Interactions

Non-Steroidal Anti-Inflammatory Agents (NSAIDs) and Selective COX-2 Inhibitors Co-administration of NSAIDs, including selective COX-2 inhibitors, with candesartan may lead to renal function deterioration, particularly in elderly patients, those who are volume-depleted, or individuals with compromised renal function. This may result in acute renal failure, although these effects are generally reversible. It is advisable to monitor renal function periodically in patients receiving both candesartan and NSAID therapy. Additionally, the antihypertensive effect of candesartan may be diminished by NSAIDs.

Lithium Concomitant use of lithium with candesartan has been associated with increased serum lithium concentrations and potential toxicity. Monitoring of serum lithium levels is recommended during co-administration.

Dual Blockade of the Renin-Angiotensin System (RAS) The combination of candesartan with other agents that affect the RAS, such as ACE inhibitors or aliskiren, may increase the risk of hypotension, hyperkalemia, and renal function changes, including acute renal failure. Close monitoring of blood pressure, renal function, and electrolytes is essential in patients receiving this combination therapy.

Potassium-Sparing Diuretics and Potassium Supplements Co-administration of candesartan with potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes may lead to hyperkalemia. Serum potassium levels should be monitored in these patients.

Alcohol, Barbiturates, and Narcotics The use of alcohol, barbiturates, or narcotics may enhance the risk of orthostatic hypotension when taken with candesartan.

Antidiabetic Drugs Adjustment of the dosage of antidiabetic medications may be necessary when used concurrently with candesartan.

Pharmacokinetic Interactions

Ion Exchange Resins The absorption of hydrochlorothiazide, when administered with cholestyramine or colestipol, may be significantly reduced. It is recommended to stagger the administration of hydrochlorothiazide and ion exchange resins, ensuring hydrochlorothiazide is taken at least 4 hours before or 4-6 hours after the resins.

Other Interactions

Skeletal Muscle Relaxants Increased responsiveness to nondepolarizing skeletal muscle relaxants, such as tubocurarine, may occur when used with candesartan.

Digitalis Thiazide-induced hypokalemia or hypomagnesemia may increase the risk of digoxin toxicity. Monitoring of potassium and magnesium levels is advisable.

Noradrenaline Thiazides may reduce arterial responsiveness to noradrenaline; however, this effect is not sufficient to negate the therapeutic efficacy of noradrenaline.

Steroids and Adrenocorticotropic Hormone (ACTH) Hypokalemia may develop during concurrent use of steroids or ACTH.

Cytotoxic Products Thiazides may decrease the renal excretion of cytotoxic agents, such as cyclophosphamide and methotrexate, potentially enhancing their myelosuppressive effects.

Cyclosporine The concomitant use of cyclosporine with candesartan may elevate the risk of hyperuricemia and complications related to gout.

Contraindications

Aliskiren should not be co-administered with candesartan in patients with diabetes or those with renal impairment (GFR <60 mL/min).

Packaging & NDC

The table below lists all NDC Code configurations of Candesartan Cilexetil and Hydrochlorothiazide, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Pediatric patients, particularly neonates with a history of in utero exposure to candesartan cilexetil and hydrochlorothiazide tablets, may experience specific complications. In cases of oliguria or hypotension, it is crucial to prioritize the support of blood pressure and renal perfusion. Interventions such as exchange transfusions or dialysis may be necessary to address hypotension and/or to compensate for impaired renal function.

The safety and effectiveness of candesartan cilexetil and hydrochlorothiazide tablets in pediatric patients have not been established. Therefore, caution is advised when considering this treatment in the pediatric population.

Geriatric Use

Elderly patients (≥ 65 years) have been the subject of pharmacokinetic studies regarding candesartan. Findings indicate that the plasma concentration of candesartan is elevated in this population, with a maximum concentration (C_max) approximately 50% higher and an area under the curve (AUC) approximately 80% higher compared to younger subjects receiving the same dosage.

Despite these increased plasma levels, the pharmacokinetics of candesartan remain linear in elderly patients, and neither candesartan nor its inactive metabolite accumulates in the serum with repeated once-daily administration. Consequently, no initial dosage adjustment is necessary for elderly patients.

Healthcare providers should remain vigilant when prescribing candesartan to geriatric patients, considering the potential for increased exposure and monitoring for any adverse effects.

Pregnancy

There is no specific information regarding the use of this medication during pregnancy, including safety concerns, dosage modifications, or special precautions. Healthcare professionals should consider the lack of data when prescribing this medication to pregnant patients. The potential risks and benefits should be carefully evaluated, and alternative treatments may be considered in consultation with the patient. Women of childbearing potential should be advised to discuss their pregnancy status and any plans for pregnancy with their healthcare provider prior to initiating treatment.

Lactation

It is not known whether candesartan is excreted in human milk; however, it has been demonstrated to be present in rat milk. Thiazides are known to appear in human milk.

Due to the potential for adverse effects on the nursing infant, healthcare professionals should consider the importance of the drug to the lactating mother when making a decision to either discontinue nursing or discontinue the medication.

Renal Impairment

Patients with renal impairment should have their renal function monitored periodically while being treated with candesartan cilexetil and hydrochlorothiazide tablets. It is important to note that changes in renal function, including acute renal failure, may occur due to the effects of drugs that inhibit the renin-angiotensin system and diuretics.

Particular caution is warranted for patients whose renal function may be influenced by the renin-angiotensin system, such as those with renal artery stenosis, chronic kidney disease, severe heart failure, or volume depletion. These patients may be at an increased risk of developing oliguria, progressive azotemia, or acute renal failure when receiving candesartan cilexetil and hydrochlorothiazide tablets.

In cases where a clinically significant decrease in renal function is observed, it may be necessary to withhold or discontinue therapy. Additionally, in patients with heart failure, the use of candesartan cilexetil and hydrochlorothiazide tablets may lead to excessive hypotension, which can result in oliguria, azotemia, and, in rare instances, acute renal failure and death.

Therapy should be initiated under close medical supervision, with careful monitoring during the first two weeks of treatment and following any increase in the dose of candesartan or the diuretic.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the prescribing information.

Overdosage

In cases of overdosage with candesartan cilexetil, acute toxicity studies in animal models have demonstrated that no lethality was observed in mice, rats, and dogs administered single oral doses of up to 2000 mg/kg. Additionally, rats receiving a combination of candesartan cilexetil (2000 mg/kg) and hydrochlorothiazide (1000 mg/kg) also showed no lethality. However, in mice administered single oral doses of the primary metabolite, candesartan, the minimum lethal dose was found to be greater than 1000 mg/kg but less than 2000 mg/kg.

Limited clinical data are available regarding human overdosage with candesartan cilexetil. The most likely manifestations of an overdose may include hypotension, dizziness, and tachycardia. In some cases, bradycardia may occur due to parasympathetic (vagal) stimulation. Should symptomatic hypotension arise, it is imperative to initiate supportive treatment promptly.

For hydrochlorothiazide, the predominant signs and symptoms associated with overdosage are typically those resulting from electrolyte depletion, including hypokalemia, hypochloremia, and hyponatremia, as well as dehydration due to excessive diuresis. If digitalis has been co-administered, hypokalemia may exacerbate the risk of cardiac arrhythmias.

It is important to note that candesartan is not removed by hemodialysis, and the extent to which hydrochlorothiazide is removed by this method has not been established.

For the most current information regarding the management of overdose, healthcare professionals are advised to consult their Regional Poison Control Center. Contact numbers for certified poison control centers can be found in the Physicians’ Desk Reference (PDR). In managing overdose cases, it is crucial to consider the potential for multiple-drug overdoses, drug-drug interactions, and altered pharmacokinetics in the patient.

Nonclinical Toxicology

Fertility and reproductive performance were evaluated in studies involving male and female rats administered oral doses of up to 300 mg candesartan cilexetil/kg/day, which is approximately 83 times the maximum daily human dose based on body surface area. The results indicated no adverse effects on fertility. Additionally, hydrochlorothiazide did not adversely affect the fertility of either sex in mice and rats, with doses administered via diet of up to 100 mg/kg and 4 mg/kg, respectively, prior to conception and throughout gestation.

No carcinogenicity studies have been conducted with the combination of candesartan cilexetil and hydrochlorothiazide. However, candesartan cilexetil was administered orally to mice and rats for up to 104 weeks at doses of up to 100 mg/kg/day and 1000 mg/kg/day, respectively, with no evidence of carcinogenicity observed. The administration routes differed, with rats receiving the drug by gavage and mice via dietary administration. The systemic exposures achieved were significantly higher than those in humans at the maximum recommended daily dose of 32 mg. Furthermore, two-year feeding studies conducted by the National Toxicology Program (NTP) revealed no carcinogenic potential for hydrochlorothiazide in female mice at doses up to approximately 600 mg/kg/day or in male and female rats at doses up to approximately 100 mg/kg/day. However, the NTP did find equivocal evidence for hepatocarcinogenicity in male mice.

In terms of mutagenicity, candesartan cilexetil and its active metabolite, candesartan, tested positive in vitro in the Chinese hamster lung (CHL) chromosomal aberration assay and the mouse lymphoma mutagenicity assay. The combination of candesartan cilexetil and hydrochlorothiazide tested negative for mutagenicity in the Ames test, unscheduled DNA synthesis in rat liver, chromosomal aberrations in rat bone marrow, and micronuclei in mouse bone marrow. Both candesartan and its O-deethyl metabolite were positive for genotoxicity in the in vitro CHL chromosomal aberration assay, but neither compound was positive in the Ames test or the in vitro mouse lymphoma cell assay. Candesartan was also evaluated in vivo in the mouse micronucleus test and in vitro in the Chinese hamster ovary (CHO) gene mutation assay, yielding negative results in both cases. Candesartan cilexetil was similarly evaluated in the Ames test, the in vitro mouse lymphoma cell assay, the in vivo rat hepatocyte unscheduled DNA synthesis assay, and the in vivo mouse micronucleus test, all with negative outcomes.

When hydrochlorothiazide was tested alone, it produced positive results in vitro in the CHO sister chromatid exchange (clastogenicity) and mouse lymphoma cell (mutagenicity) assays, as well as in the Aspergillus nidulans non-disjunction assay. However, it was not found to be genotoxic in vitro in the Ames test for point mutations, the CHO test for chromosomal aberrations, or in vivo in assays involving mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene.

Postmarketing Experience

Very rarely, the following events have been reported in the postmarketing experience with candesartan cilexetil:

Abnormal hepatic function and hepatitis have been noted under digestive disorders. Hematologic events include neutropenia, leukopenia, and agranulocytosis. Immunologic reactions such as angioedema have also been documented. Metabolic and nutritional disorders reported include hyperkalemia and hyponatremia. Additionally, respiratory system disorders such as cough have been observed. Skin and appendages disorders, including pruritus, rash, and urticaria, have been reported as well.

Furthermore, rare cases of rhabdomyolysis have been associated with the use of angiotensin II receptor blockers.

Patient Counseling

Healthcare providers should advise patients to discontinue candesartan cilexetil and hydrochlorothiazide tablets as soon as pregnancy is detected. It is important to inform patients that medications acting directly on the renin-angiotensin system can cause injury and even death to a developing fetus.

Patients should be made aware that lightheadedness may occur, particularly during the initial days of therapy, and they should report this symptom to their prescribing physician. In the event of syncope, patients must discontinue the medication and consult their physician before resuming treatment.

Healthcare providers should emphasize that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to a significant drop in blood pressure, which may result in lightheadedness or syncope. Patients should be instructed not to use potassium supplements, salt substitutes containing potassium, or any other medications that may elevate serum potassium levels without prior consultation with their physician.

For those taking hydrochlorothiazide, it is essential to instruct patients to protect their skin from sun exposure and to undergo regular skin cancer screenings. Female patients of childbearing age should be informed about the potential consequences of exposure to candesartan cilexetil and hydrochlorothiazide tablets during pregnancy. Providers should discuss treatment options with women who are planning to become pregnant and encourage patients to report any pregnancies to their physicians as soon as possible.

Finally, healthcare providers should ensure that serum electrolytes are monitored periodically to maintain patient safety and treatment efficacy.

Storage and Handling

The product is supplied in a container that must be kept tightly closed to maintain integrity. It should be stored at a temperature range of 20 to 25°C (68 to 77°F), with permissible excursions between 15 to 30°C (59 to 86°F) as defined by USP Controlled Room Temperature guidelines.

Additional Clinical Information

Patients receiving candesartan cilexetil and hydrochlorothiazide tablets should be informed about the potential for lightheadedness, particularly during the initial days of therapy, and the importance of reporting this to their prescribing physician. In cases of syncope, patients are advised to discontinue the medication until consulting with their physician. Clinicians should counsel patients on the risks associated with inadequate fluid intake, excessive perspiration, diarrhea, or vomiting, which may lead to significant drops in blood pressure, resulting in lightheadedness or syncope. Additionally, patients should be cautioned against using potassium supplements, salt substitutes containing potassium, or other medications that may elevate serum potassium levels without prior consultation with their physician. Those taking hydrochlorothiazide should also be advised to protect their skin from sun exposure and to undergo regular skin cancer screenings.

In post-marketing experience, very rare adverse events associated with candesartan cilexetil have been reported, including abnormal hepatic function, hepatitis, neutropenia, leukopenia, agranulocytosis, angioedema, hyperkalemia, hyponatremia, cough, pruritus, rash, and urticaria. There have also been rare reports of rhabdomyolysis in patients receiving angiotensin II receptor blockers.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Candesartan Cilexetil and Hydrochlorothiazide as submitted by Solco Healthcare LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)