Overview:
Candesartan cilexetil is a drug used to treat hypertension or high blood pressure. It is available as oral tablets. Candesartan cilexetil is an ARB (angiotensin receptor blocker). It acts by blocking the action of the receptor. The Food and Drug Administration (FDA) approved Candesartan cilexetil to treat hypertension in June 1998.
Candesartan is also used off-label to treat migraines, left ventricular hypertrophy, diabetic nephropathy, and cerebrovascular accident or stroke. Avoid activities requiring mental alertness while taking this drug, as it may cause drowsiness and dizziness. Report to the doctor if any side effects are experienced after the start of the drug therapy.
How Does Candesartan Cilexetil Work?
Candesartan cilexetil is an angiotensin-II receptor blocker. It acts by binding to the angiotensin-II receptors in the body. The resultant effect is dilation of the blood vessels, thus bringing down the blood pressure. As a result, the heart receives more blood and oxygen and decreases blood pressure. Bringing down high blood pressure reduces the risk of heart attacks, kidney issues, and strokes.
Dosage:
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The adult dosing of Candesartan cilexetil begins at 8 mg tablet once daily.
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The dose of the medication will be further increased or decreased by the doctor depending on the response to the medication by monitoring the blood pressure levels.
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Take this medication by mouth once daily, generally with or without a meal, as prescribed by the doctor.
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In case of any queries, the patient is advised to contact the doctor or pharmacist.
Warnings:
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Hypotension: Patients who have experienced extended diuretic medication, dietary salt restriction, diarrhea, dialysis, or vomiting are more susceptible to developing symptoms of hypotension or a decrease in blood pressure. Patients with symptomatic hypotension may need their drug doses, medications belonging to the diuretic class, or both temporarily decreased in addition to fluid replacement. Hence, monitoring of blood pressure levels is required in these patients.
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Impaired Kidney Function: Drugs of the ARB class have been reported to cause changes in kidney function, including acute kidney disease. Such patients are more susceptible to exhibiting symptoms such as decreased urine output (oliguria), elevations in the laboratory parameters of the kidney function test, etc. The drug may be discontinued in these cases.
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Toxicity to The Fetus: Candesartan cilexetil is a pregnancy category D drug. Administration of the medication during the second and third trimesters of pregnancy has been associated with potential risk to the fetus. It has been shown to increase the risk of toxicity or death. Hence, pregnant women with reproductive potential or who intend to get pregnant should inform the doctor before starting the therapy with Candesartan cilexetil.
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Hyperkalemia: Candesartan cilexetil has been shown to increase potassium levels. Hence, close monitoring of potassium is required while on therapy with the drug.
For Patients
What Is Hypertension or High Blood Pressure?
Hypertension is a condition in which blood pressure is elevated. Various factors like age, obesity, and genetics can cause it. Some other factors that can contribute to hypertension are high sodium intake, lack of physical activity, and alcohol consumption.
The prevalence of hypertension in the United States is more than 30 %. The burden of hypertension and its consequences on society is significant. It can lead to heart attacks, strokes, and kidney failure. Many factors attributed to the increased prevalence of high blood pressure, such as poor diet, lack of physical activity, and alcohol consumption, have been linked to the phenomenon. Prolonged to be exposed to smoking has been found to increase the risk of developing hypertension.
Many symptoms can indicate hypertension, like headaches, dizziness, blurred vision, nosebleeds, and chest pain. There are a variety of treatments for hypertension, such as lifestyle changes, medications, and others.
Learn About Candesartan Cilexetil:
When and Why to Take Candesartan Cilexetil?
Candesartan cilexetil is a prescription medication used to treat high blood pressure in adults and children between the age of 6 to 18 years. Candesartan cilexetil may be taken either with or without food. The drug should be swallowed along with a glass of water. It is important to follow the instructions given by the doctor and to adhere to the therapy strictly, and the medication should be administered daily. In case of any doubts, always seek help from a medical professional.
How Effective Is Candesartan Cilexetil?
Candesartan cilexetil is a well-tolerated drug that has proven to be effective in controlling high blood pressure within three to four weeks since the start of the therapy. The effect is sustained on long-term use of the drug to control hypertension.
What Are the Things to Inform the Doctor Before Taking Candesartan Cilexetil?
Notify the doctor if any of the following conditions are present:
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If the patient is on dialysis or has a heart or kidney disease.
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If the patient experiences gastric problems like vomiting or recently experienced episodes of vomiting.
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If the patient has undergone a kidney transplant.
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If the patient suffers from Conn's syndrome, also known as primary hyperaldosteronism, an adrenal gland disorder.
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If the patient has experienced a stroke.
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If the patient has a history of sudden blood pressure decreases.
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If the patient thinks she is (or may become) pregnant, she should inform the doctor.
- Candesartan cilexetil is contraindicated in the first trimester of pregnancy. It should not be used if the patient is more than three months along because it could seriously harm the developing child.
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If the patient takes medications belonging to the angiotensin-converting enzyme inhibitor (ACEI) or mineralocorticoid receptor antagonists (MRA) class.
What Are the Side Effects of Candesartan Cilexetil?
Like all medications, Candesartan could have adverse effects in some patients. While they are occasionally serious, they are frequently not. The patient needs to notify the doctor if side effects are experienced.
The side effects of Candesartan cilexetil are as follows:
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Drowsiness.
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Light-headedness.
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Dizziness.
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Migraine.
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Infection of the lungs.
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Reduced blood pressure.
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Swelling of the tongue, throat, face, and lips.
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Lumpy rash on the skin (hives).
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Scratching.
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Muscle and joint pain, including back pain.
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Repulsion.
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Cough.
These symptoms are common and usually resolve on their own. However, if it persists or worsens, consult the doctor immediately.
The more severe side effects requiring immediate medical attention include
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Liver inflammation (hepatitis). Symptoms include flu-like symptoms, fatigue, and yellowing of your skin and eye whites.
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Increased potassium in the blood, particularly if you already have kidney or heart disease. The symptoms include weakness, fatigue, an erratic heartbeat, or even pins and needles if it's bad enough.
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Affects the kidneys' function, particularly if the patient already has heart failure or kidney disease. However, this is an extremely rare occurrence.
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Swelling of the face, lips, tongue, or throat may make swallowing difficult; breathing problems with or without facial, lips, tongue, or throat; and intense skin itchiness (with raised lumps).
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White blood cell count decline (agranulocytosis). The patient may experience fatigue, an infection, or a fever, and the ability to fight against infections may be reduced. Contact the physician if this occurs.
What Should Be Done if a Dose Is Missed?
If a dose is missed, take it as soon as it is remembered and continue with the normal dosing regimen. However, if it’s almost time for the next dose, skip the previous one and continue as scheduled. Avoid taking double doses to make up for a missed dose. In case of queries, contact the pharmacist or the doctor.
What Should Be Done to Treat Candesartan Cilexetil Overdose?
Avoid taking the tablet more than the advised dosage. Only take the number of tablets the doctor specified on the pharmacy label. Inform the doctor immediately if an overdose happens, or visit the local accident and emergency department.
How to Store Candesartan Cilexetil?
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Store the tablets at room temperature between 15 to 30 degrees Celsius.
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Keep the tablets away from children and pets.
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The disposal of medications in wastewater or household waste is not recommended. Check how to dispose of expired medicines, according to a pharmacist. These actions will aid in keeping the environment safe.
Avoid Self-Medication:
Avoid taking this drug without a prescription, do not recommend it to others, and do not take it on someone else's advice. Different people react to medications differently, and some may even react worse. Make a list of all the prescriptions and non-prescription that are being taken whenever consulting a doctor, and take the medication only as instructed by a qualified healthcare professional.
For Doctors
Indication:
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Treatment of hypertension in adults and children aged 1 to 17.
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Heart failure (NYHA class II to IV with ejection fraction 40 % or less) to bring down cardiovascular mortality and associated hospitalization.
Dosing:
Dosing Considerations:
Renal Impairment:
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Adult: No initial dosage adjustment is necessary.
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Moderate to Severe: 8 mg daily may be a sufficient dose.
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Pediatric: Use is not recommended.
Hepatic Impairment (Adult):
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Mild: No dosage adjustment is necessary.
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Moderate: Initiate therapy with 8 mg.
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Severe: No specific recommendations are available.
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Geriatric: No initial dosage adjustment is necessary.
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Hemodialysis: No dosage adjustment should be necessary during dialysis.
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Significant Decrease in Renal Function: Withhold or discontinue therapy.
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Symptomatic Hypotension: Temporary dosage reduction may be necessary.
Dosage Forms and Strength:
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4 mg Tablets: They are round or biconvex, white to off-white, non-film-coated, scored, and coded ACF on one side and 004 on the other.
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8 mg Tablets: They are light pink, biconvex, and non-film coated; scored tablets are coded 008 on one side and ACG on the other.
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16 mg Tablets: They are pink, circular or biconvex, uncoated, scored, non-film coated tablets are designated ACH on one side and 016 on the other.
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32 mg Tablets: They are pink, circular or biconvex, non-film coated, scored tablets marked with ACL codes and 032 on opposite sides.
Pharmacology
Mechanism of Action:
Candesartan cilexetil is a prodrug given orally, which quickly breaks down to become its active metabolite, Candesartan, following absorption in the digestive tract. By inhibiting the renin-angiotensin-aldosterone system (RAAS), Candesartan decreases blood pressure. It interferes with angiotensin II for binding to the type-1 angiotensin II receptor (AT1) subtype and counteracts angiotensin II effects on blood pressure elevation. Angiotensin-receptor blockers (ARBs) like Candesartan can be used alone or in combination with other medications to treat hypertension.
In several tissues, including vascular smooth muscle and the adrenal glands, Candesartan specifically prevents angiotensin II from binding to AT1. This lowers blood pressure by blocking angiotensin II effects on aldosterone secretion and vasoconstriction via the AT1 receptor. Candesartan is more selective for AT1 than AT2 by a factor of more than 10,000. Aldosterone secretion inhibition may increase sodium and water excretion at the expense of a decrease in potassium excretion.
Pharmacodynamics:
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Candesartan cilexetil is quickly converted during the gastrointestinal tract's absorption into Candesartan, its active metabolite. Candesartan lowers blood pressure by counteracting the hypertensive effects of angiotensin II through the RAAS.
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Angiotensin II exerts its vasoconstrictive and aldosterone-secreting actions through the G-protein coupled receptor (GPCR) AT1. Recent research suggests that by generating vasorelaxation and raising urinary sodium excretion, AT2 directly influences long-term blood pressure regulation and counteracts AT1-mediated effects.
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AT1 is inhibited by angiotensin receptor blockers (ARBs), non-peptide competitive agents. ARBs block angiotensin II's capacity to generate pressor and cell proliferative effects. ARBs do not impact bradykinin-induced vasodilation, in contrast to ACE inhibitors. ARBs generally lower blood pressure as a side effect.
Pharmacokinetics:
Absorption:
The absolute bioavailability of the drug after ingestion of the Candesartan cilexetil prodrug was calculated to be 15 %. The bioavailability of the active drug from candesartan cilexetil is unaffected by high-fat foods. The volume of distribution for Candesartan cilexetil is 0.13 L/kg.
Distribution:
Candesartan has an extensive protein binding of around 99 %; hence, it does not enter red blood cells.
Metabolism:
Candesartan is formed via the quick and thorough ester hydrolysis of the prodrug Candesartan cilexetil in the intestinal wall. Candesartan is mainly eliminated as an unaltered medication through the biliary pathway and in the feces. O-deethylation of Candesartan via cytochrome P450 2C9 results in a minor amount of hepatic metabolism (20 %) that produces an inactive metabolite. Uridine diphosphate glucuronosyltransferase 1A3 N-glucuronidates candesartan in the tetrazole ring (UGT1A3). O-glucuronidation is another possibility. Candesartan is eliminated in the urine and feces in 75 % of its unaltered form.
Excretion:
Approximately 26 % of the dose of Candesartan taken orally is excreted unaltered in the urine. The majority of Candesartan is eliminated unaltered in the urine and feces (via bile).
Active Ingredients: The active ingredient in Candesartan tablets is Candesartan Cilexetil.
Inactive Ingredients: The inactive ingredient in the Candesartan tablet is
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Hydroxypropyl cellulose.
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Polyethylene glycol.
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Lactose.
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Corn starch.
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Carboxymethylcellulose calcium.
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Magnesium stearate.
Toxicity:
Non-clinical Toxicity:
Candesartan cilexetil has not been reported to cause carcinogenesis or impairment in fertility, as evidenced by animal studies.
Clinical Toxicity:
Clinical toxicity is an extension of the pharmacological activity and is presented with excessive antagonism of angiotensin receptors causing hypotension or vasodilation.
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Treatment of Mild to Moderate Toxicity: Muscle cramps, vertigo, asymptomatic hypoglycemia, mild hypotension, and tachycardia have all been recorded. With parasympathetic (vagal) activation, bradycardia may happen. IV fluids manage it for hypotension.
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Treatment of Severe Toxicity: Another ARB drug (Valsartan) overdose has been associated with circulatory collapse, shock, and a reduction in consciousness. Management includes consideration of activated charcoal for decontamination.
Monitoring Parameters:
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Renal Function: Periodically throughout treatment, especially in patients using NSAIDs or additional medications that affect the renin-angiotensin system.
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Blood Pressure: In patients receiving concurrent renin-angiotensin system-affecting medications, closely monitor them during dose escalation and at regular intervals throughout treatment.
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Serum Potassium Levels: Periodically throughout treatment, especially when a patient only uses potassium-sparing diuretics, potassium supplements, salt replacements that include potassium, or other medications that elevate serum potassium levels.
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Serum Electrolyte Levels: In patients receiving concomitant agents that affect the renin-angiotensin system
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Hypertension: Especially in patients at risk for orthostatic hypotension and other negative effects at regular intervals (e.g., older or with postural symptoms).
Warnings and Precautions:
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Cardiovascular: Hypotension can happen following major surgery and anesthesia, especially in individuals who are dehydrated or have lost a lot of sodium or volume. Correct volume and salt depletion should be done before usage, and therapy should be monitored; a dose reduction may be necessary.
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Hepatic: Moderate hepatic impairment; consider dose reduction
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Renal: In particular in patients whose renal function depends on the RAS (e.g., renal artery stenosis, chronic renal disease, severe heart failure, or volume depletion), drugs that inhibit the renin-angiotensin system (RAS) may cause changes in renal function, including acute renal failure; monitoring is advised, and therapy interruption or discontinuation may be necessary.
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Concurrent Use: Aliskiren; avoid in patients with GFR below 60 mL/min. ACE inhibitors plus mineralocorticoid receptor antagonists are not recommended.
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Endocrine and Metabolic: Monitoring is advised because hyperkalemia can happen, especially in individuals taking potassium-sparing diuretics, potassium supplements, potassium-containing salt replacements, or other medications that increase serum potassium levels.
Contraindications:
Candesartan cilexetil is contraindicated in patients with
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A known history of hypersensitivity to the drug or its components.
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Along with Aliskrein in diabetic patients.
Clinical Studies:
With patients who had diastolic blood pressures of 95 to 114 mm Hg at baseline, the antihypertensive effects of the drug were studied in 14 placebo-controlled trials with durations ranging from 4 to 12 weeks. The daily doses used were primarily 2 to 32 mg.
Candesartan cilexetil was investigated mostly as a single agent, but it was also evaluated in combination with Hydrochlorothiazide and Amlodipine. In these investigations, 1027 patients received a placebo, and 2350 patients were randomly assigned to one of multiple Candesartan cilexetil doses.
Results: These patients did not experience any inflated first-dose effects. Following the initial dosage, most of the antihypertensive impact was noticed in two weeks, and the full effect was in four weeks. Blood pressure effects from a once-daily dose were sustained for 24 hours, with trough-to-peak ratios of blood pressure effects typically exceeding 80 %. When combined with Hydrochlorothiazide, Candesartan cilexetil exhibited an additional blood pressure-lowering impact.
Drug Interactions:
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NSAIDs Including COX-2 Inhibitors: Coadministration of NSAIDs (non-steroidal anti-inflammatory agents), including selective COX-2 (cyclooxygenase-2) inhibitors, with angiotensin II receptor antagonists, such as Candesartan, may deteriorate renal function in patients who are elderly, volume-depleted (including those receiving diuretic therapy), or with compromised renal function, including potential acute renal failure. Usually, these effects are reversible. Patients on Candesartan and NSAID therapy should have their renal function checked periodically. These drugs may have less of an antihypertensive impact when used with NSAIDs, such as selective COX-2 inhibitors.
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Lithium: When used concurrently with angiotensin II receptor antagonists such as Candesartan cilexetil, Lithium has been shown to increase serum lithium concentrations and be hazardous. Hence, monitoring is required.
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Drugs Affecting the RAAS System: Compared to monotherapy, dual blockade of the RAS with ACE inhibitors, Aliskiren, or angiotensin receptor blockers increases the risk of hypotension, hyperkalemia, and abnormalities in renal function (including acute renal failure). Patients on Candesartan cilexetil and other RAS-affecting medications should closely monitor their blood pressure, kidney function, and electrolytes.
Other Specifications:
Candesartan Cilexetil in Pregnant Women:
Avoid use in pregnancy due to potential risk to the fetus.
Candesartan Cilexetil in Lactating Women:
Although it has been demonstrated that Candesartan cilexetil is present in rat milk, it is unknown whether candesartan is excreted in human milk.
Given the possibility of harmful effects on the nursing infant, a choice should be made regarding whether to stop nursing or stop using the drug, considering the significance of the medication to the mother.
Candesartan Cilexetil in Geriatric Patients:
The pharmacokinetics of Candesartan was found to be linear in the elderly, and repeated once-daily treatment did not cause Candesartan or its inactive metabolite to accumulate in the serum of these participants. No initial dosage modification is required.
