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Overview

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Name

Candesartan Cilexetil + Hydrochlorothiazide

Precaution

The combination of Candesartan Cilexetil and Hydrochlorothiazide is primarily used to treat hypertension (high blood pressure) and is also beneficial for patients with heart failure or fluid retention. However, there are several important precautions to consider before using this medication. Both components of the combination have effects on electrolyte balance, so regular monitoring of electrolytes, especially potassium and sodium levels, is essential to avoid imbalances that could lead to serious complications like arrhythmias. Candesartan may increase potassium levels (hyperkalemia), while hydrochlorothiazide is a diuretic that may lower potassium levels (hypokalemia), creating a potential for dangerous electrolyte disturbances. This combination should be used cautiously in patients with renal impairment, as both drugs are processed by the kidneys and could exacerbate kidney problems. Blood pressure should be closely monitored, especially during the initial stages of therapy, as the combination of an ACE inhibitor or ARB (angiotensin receptor blocker) with a diuretic may lead to significant drops in blood pressure. In patients with a history of dehydration or those on other diuretics, there is an increased risk of electrolyte imbalances and dehydration, so proper hydration and electrolyte monitoring are necessary. This medication should not be used during pregnancy, as it may harm the fetus, particularly during the second and third trimesters, and it should be avoided during breastfeeding due to the potential effects on the infant.

Indication

The combination of Candesartan Cilexetil and Hydrochlorothiazide is indicated for the treatment of hypertension (high blood pressure). Candesartan, an angiotensin II receptor blocker (ARB), works by relaxing blood vessels, reducing blood pressure, while Hydrochlorothiazide, a thiazide diuretic, helps the body eliminate excess salt and water, further aiding in blood pressure reduction. In addition to hypertension, this combination may be used in patients with heart failure to reduce symptoms related to fluid retention and to improve overall cardiovascular function. It can also be beneficial in patients with chronic kidney disease (CKD) or those who have diabetes and hypertension, as the ARB (candesartan) helps protect kidney function while lowering blood pressure. Off-label, this combination may also be used in conditions such as edema (fluid retention) where diuresis is required, although this should be done under strict medical supervision to monitor fluid and electrolyte balance.

Contra indication

Candesartan Cilexetil and Hydrochlorothiazide should not be used in patients who have a known allergy to either of the components, including angiotensin II receptor antagonists, thiazide diuretics, or any of the excipients in the formulation. This combination is contraindicated in patients with a history of angioedema related to prior use of ACE inhibitors or ARBs. It should not be used in patients with severe renal impairment or those with conditions such as anuria (lack of urine production) or acute renal failure, as the diuretic effect may exacerbate kidney dysfunction. The use of this combination is also contraindicated during pregnancy, particularly in the second and third trimesters, as it can cause harm to the developing fetus, including renal dysfunction and oligohydramnios (low amniotic fluid). Additionally, it should not be used during breastfeeding as both components can pass into breast milk and pose a risk to the infant. Patients with a history of electrolyte disturbances, such as hyperkalemia (high potassium levels) or hyponatremia (low sodium levels), should avoid using this combination, as hydrochlorothiazide and candesartan together can cause further imbalances in electrolytes.

Side Effect

The most common side effects associated with Candesartan Cilexetil and Hydrochlorothiazide include dizziness, fatigue, and headache. These effects are generally mild and may improve as the body adjusts to the medication. Both components may also lead to electrolyte disturbances, including hypokalemia (low potassium levels), hyperkalemia (high potassium levels), and hyponatremia (low sodium levels), which require regular monitoring of electrolyte levels. In rare cases, more severe side effects may occur, such as: - **Kidney dysfunction**: Both Candesartan and Hydrochlorothiazide can cause or worsen kidney problems. Symptoms of kidney dysfunction may include swelling in the legs, feet, or ankles, fatigue, and changes in urination. Renal function should be monitored regularly. - **Hypotension (low blood pressure)**: A significant drop in blood pressure, particularly after the first dose or a dose increase, may occur. Symptoms can include dizziness, lightheadedness, or fainting, especially when standing up quickly. Adjusting the dose or adding other medications may be necessary if this occurs. - **Angioedema**: A rare but serious allergic reaction that causes swelling of the face, tongue, or throat, leading to difficulty breathing. Angioedema requires immediate medical attention and discontinuation of the medication. - **Hyperglycemia (high blood sugar)**: Hydrochlorothiazide can cause mild increases in blood sugar levels, which may be problematic for patients with diabetes or those at risk of developing diabetes.

Pregnancy Category ID

4

Mode of Action

Candesartan Cilexetil works as an angiotensin II receptor blocker (ARB), which means it blocks the action of angiotensin II, a potent vasoconstrictor. Angiotensin II normally constricts blood vessels, increasing blood pressure. By inhibiting this action, candesartan causes blood vessels to relax, leading to a decrease in blood pressure. Candesartan also reduces the release of aldosterone, a hormone that promotes sodium retention and fluid balance, further contributing to blood pressure reduction. Hydrochlorothiazide is a thiazide diuretic that works by inhibiting sodium reabsorption in the kidneys. This leads to increased excretion of sodium, chloride, and water, which reduces blood volume and, in turn, lowers blood pressure. Additionally, the reduction in fluid retention can be helpful in conditions such as heart failure and edema. Together, Candesartan and Hydrochlorothiazide have a complementary effect: Candesartan decreases vasoconstriction, while Hydrochlorothiazide reduces fluid volume. This dual mechanism provides effective management of hypertension and fluid overload.

Interaction

Candesartan Cilexetil and Hydrochlorothiazide may interact with a variety of medications, potentially altering their effectiveness or increasing the risk of side effects. - **Antihypertensive medications**: The combination with other antihypertensive agents, such as ACE inhibitors, ARBs, beta-blockers, or calcium channel blockers, can lead to excessive blood pressure lowering, which may result in dizziness, fainting, or syncope (fainting). Blood pressure should be carefully monitored, especially when starting treatment or adjusting doses. - **Potassium supplements and potassium-sparing diuretics**: Candesartan may increase potassium levels, and Hydrochlorothiazide can decrease potassium levels. Co-administration of potassium supplements or potassium-sparing diuretics (e.g., spironolactone) may lead to hyperkalemia (high potassium), which could cause serious cardiac arrhythmias. Routine monitoring of potassium levels is advised when using these medications together. - **Lithium**: Lithium, a drug used for bipolar disorder, has a narrow therapeutic index, and its levels may increase when taken with this combination. Elevated lithium levels can lead to toxicity, with symptoms such as nausea, vomiting, tremors, and confusion. If lithium is used concurrently, close monitoring of lithium levels is essential. - **NSAIDs (Nonsteroidal Anti-inflammatory Drugs)**: Concurrent use of NSAIDs (e.g., ibuprofen) can reduce the antihypertensive effect of both candesartan and hydrochlorothiazide, as NSAIDs can reduce renal blood flow and impair the effects of diuretics. Prolonged use of NSAIDs can also increase the risk of kidney damage in patients using this combination.

Pregnancy Category Note

Pregnancy Category: C (1st trimester); D (2nd and 3rd trimesters)

Adult Dose

The usual starting dose for adults with hypertension is 16 mg of Candesartan Cilexetil combined with 12.5 mg of Hydrochlorothiazide once daily. Depending on the patient’s blood pressure response, the dose can be increased up to 32 mg of Candesartan and 25 mg of Hydrochlorothiazide once daily. The maximum recommended dose for most patients is 32 mg of Candesartan and 25 mg of Hydrochlorothiazide daily. For patients with heart failure, the initial dose is often 4 mg of Candesartan combined with 12.5 mg of Hydrochlorothiazide, with gradual increases to the target dose as tolerated. It is important to start with lower doses in older patients or those with renal impairment.

Child Dose

The use of Candesartan Cilexetil and Hydrochlorothiazide in children is not well-established, and the combination is typically not recommended in pediatric populations under the age of 18 unless under the strict supervision of a healthcare provider. In some cases, lower doses of Candesartan and Hydrochlorothiazide may be considered for children with specific conditions like hypertension, but the treatment must be carefully tailored and monitored for potential side effects such as electrolyte imbalances, kidney function, and growth effects. Always consult a pediatrician for any off-label pediatric use.

Renal Dose

In patients with mild to moderate renal impairment (creatinine clearance ≥30 mL/min), no significant dose adjustments are typically required. However, kidney function should be closely monitored, as both Candesartan and Hydrochlorothiazide can affect renal function. In patients with severe renal impairment (creatinine clearance <30 mL/min) or those with end-stage renal disease on dialysis, this combination may not be suitable due to potential complications with electrolyte imbalances and kidney function. If the drug is used, careful monitoring of renal function, electrolytes, and blood pressure is critical.

Administration

Information not available