Bisoprolol Fumarate + Hydrochlorothiazide

Introduction

Bisoprolol Fumarate and Hydrochlorothiazide is a combination medication used to treat high blood pressure (hypertension). Bisoprolol is a beta-blocker that reduces the workload on the heart, while Hydrochlorothiazide is a thiazide diuretic (water pill) that helps the kidneys eliminate excess fluid and salt from the body. This combination works synergistically to lower blood pressure more effectively than either drug alone.

Uses

This combination drug is primarily used to treat:

• Hypertension (high blood pressure)

Lowering blood pressure helps reduce the risk of heart attacks, strokes, and kidney problems.

Brand Name	Bisoprolol Fumarate + Hydrochlorothiazide
Type
Weight
Generic	Bisoprolol Fumarate + Hydrochlorothiazide
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Available in	English বাংলা

Mechanism of Action

• Bisoprolol Fumarate: Bisoprolol selectively blocks β1-adrenergic receptors in the heart, reducing heart rate, the force of contraction, and cardiac output, thereby lowering blood pressure.
• Hydrochlorothiazide: Hydrochlorothiazide inhibits sodium reabsorption in the distal tubules of the kidneys, increasing the excretion of sodium, water, potassium, and hydrogen ions, which decreases blood volume and, consequently, blood pressure.

How Long Does It Take to Work?

The antihypertensive effects of the Bisoprolol and Hydrochlorothiazide combination can be observed within a few hours of administration, with maximum effects typically seen within 1 to 2 weeks of consistent use.

Absorption

Both Bisoprolol and Hydrochlorothiazide are well absorbed following oral administration. Bisoprolol has an oral bioavailability of approximately 80%, and Hydrochlorothiazide has a bioavailability of 65-75%.

Route of Elimination

Bisoprolol is eliminated through both the kidneys (50%) and the liver (50%). Hydrochlorothiazide is primarily excreted unchanged in the urine.

Dosage

Bisoprolol is an effective treatment of hypertension in once-daily doses of 2.5 to 40 mg, while Hydrochlorothiazide is effective in doses of 12.5 to 50 mg. In clinical trials of Bisoprolol/Hydrochlorothiazide combination therapy using Bisoprolol doses of 2.5 to 20 mg and Hydrochlorothiazide doses of 6.25 to 25 mg, the antihypertensive effects increased with increasing doses of either component.

Initial Therapy: Antihypertensive therapy may be initiated with the lowest dose of this conbination, one 2.5/6.25 mg tablet once daily. Subsequent titration (14 day intervals) may be carried out with this tablets up to the maximum recommended dose 20/12.5 mg once daily, as appropriate.

Replacement Therapy: The combination may be substituted for the titrated individual components.

Therapy Guided by Clinical Effect: A patient whose blood pressure is not adequately controlled with 2.5-20 mg Bisoprolol daily may instead be given this conbination. Patients whose blood pressures are adequately controlled with 50 mg of hydrochlorothiazide daily, but who experience significant potassium loss with this regimen, may achieve similar blood pressure control without electrolyte disturbance if they are switched to this conbination.

The usual dose for adults is:

• Starting dose: Bisoprolol 2.5-5 mg + Hydrochlorothiazide 6.25 mg once daily.
• Maintenance dose: Adjusted based on patient response, but typically does not exceed Bisoprolol 20 mg + Hydrochlorothiazide 12.5 mg per day.

Dosage adjustments are made based on blood pressure response and tolerance. Always follow the specific recommendations of a healthcare provider.

Administration

The drug is administered orally, once daily, preferably in the morning to prevent nighttime urination due to the diuretic effect of Hydrochlorothiazide. It can be taken with or without food.

Side Effects

Common side effects include:

• Dizziness or lightheadedness (especially when standing)
• Fatigue
• Nausea
• Headache
• Increased urination (due to the diuretic effect)

Serious side effects may include:

• Bradycardia (slow heart rate)
• Hypotension (low blood pressure)
• Electrolyte imbalances (e.g., low potassium or sodium levels)
• Heart failure exacerbation

Toxicity

Overdose of Bisoprolol may result in severe bradycardia, hypotension, bronchospasm, or acute heart failure, while Hydrochlorothiazide overdose can cause electrolyte imbalances, dehydration, and low blood pressure. Treatment involves supportive measures, such as fluid replacement and electrolyte correction.

Precautions

• Bisoprolol should be used cautiously in patients with a history of bronchospastic disease, as it can cause bronchoconstriction.
• Hydrochlorothiazide may cause electrolyte imbalances, including hypokalemia and hyponatremia, and requires regular monitoring of serum electrolytes.
• Patients with diabetes should monitor their blood sugar closely, as Hydrochlorothiazide can raise blood sugar levels.

Interaction

• Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): May reduce the antihypertensive effects of both Bisoprolol and Hydrochlorothiazide.
• Calcium Channel Blockers: Increased risk of bradycardia when used with Bisoprolol.
• Corticosteroids: May increase the risk of electrolyte imbalances when used with Hydrochlorothiazide.

Disease Interaction

• Use cautiously in patients with bronchospastic diseases, as Bisoprolol can cause bronchoconstriction.
• Patients with gout may experience exacerbations due to Hydrochlorothiazide increasing uric acid levels.
• Electrolyte imbalances should be closely monitored, especially in patients with renal impairment.

Drug Interaction

Both Bisoprolol and Hydrochlorothiazide have several drug interactions:

• Digoxin: Increased risk of bradycardia when used with Bisoprolol.
• ACE inhibitors: May enhance the antihypertensive effects of Bisoprolol and Hydrochlorothiazide.
• Antidiabetic medications: Hydrochlorothiazide may reduce the effectiveness of antidiabetic drugs.

Food Interactions

No significant food interactions are known. However, patients should maintain adequate hydration and avoid excessive salt intake, which may reduce the effectiveness of Hydrochlorothiazide.

Pregnancy Use

This combination drug is not recommended during pregnancy, especially in the second and third trimesters, due to the potential risks of fetal harm, such as growth retardation, neonatal hypotension, and electrolyte disturbances. It should be used only if clearly necessary and prescribed by a healthcare provider.

Lactation Use

Hydrochlorothiazide is excreted in breast milk in small amounts, while Bisoprolol is excreted in higher amounts. The combination is not recommended for use during breastfeeding, as it may affect milk production and pose a risk to the infant.

Acute Overdose

Symptoms of overdose may include severe hypotension, bradycardia, electrolyte imbalances, dehydration, and renal impairment. Treatment includes gastric lavage, administration of activated charcoal, intravenous fluids, and electrolyte correction. Atropine may be administered for bradycardia, and glucagon for severe hypotension.

Contraindication

This combination drug is contraindicated in patients with:

• Severe bradycardia
• Heart block greater than first degree (without a pacemaker)
• Decompensated heart failure
• Hypersensitivity to Bisoprolol, Hydrochlorothiazide, or sulfonamide-derived drugs
• Severe renal impairment (for Hydrochlorothiazide)

Use Direction

The medication should be taken once daily, preferably in the morning, with or without food. Patients should not discontinue the drug abruptly, as it may cause rebound hypertension or worsening of heart failure. Dose adjustments may be necessary based on blood pressure and heart rate.

Storage Conditions

Store the medication at room temperature, between 20°C and 25°C (68°F to 77°F), in a tightly sealed container, protected from light and moisture. Keep out of reach of children.

Volume of Distribution

• Bisoprolol: 3.5 L/kg, indicating moderate tissue distribution.
• Hydrochlorothiazide: 3.6-7.8 L/kg, indicating widespread distribution in body tissues.

Half Life

• Bisoprolol: 9 to 12 hours, allowing for once-daily dosing.
• Hydrochlorothiazide: 6 to 15 hours, depending on renal function.

Clearance

• Bisoprolol: Approximately 15.6 mL/min/kg, cleared via renal and hepatic pathways.
• Hydrochlorothiazide: Primarily eliminated by the kidneys, with clearance influenced by renal function.

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