Bisoprolol Fumarate + Hydrochlorothiazide

Bisoprolol + Hydrochlorothiazide is a fixed-combination tablet used for the treatment of hypertension. It contains Bisoprolol Fumarate (a beta-blocker) and Hydrochlorothiazide (a thiazide diuretic).

Bisoprolol is a cardioselective β1-adrenoceptor blocker that slows heart rate and improves cardiac pumping efficiency. Hydrochlorothiazide is a thiazide diuretic that removes excess water and salt from the body, lowering blood pressure. The antihypertensive effects of these agents are additive; Hydrochlorothiazide 6.25 mg significantly increases the antihypertensive effect of Bisoprolol.

This combination is indicated for the treatment of hypertension when patients are adequately controlled with individual components or when a single medication is not effective.

• Hypertension (high blood pressure)

Bisoprolol: Selectively blocks β1-receptors, reducing heart rate and myocardial contractility, thereby lowering blood pressure and decreasing myocardial oxygen demand.

Hydrochlorothiazide: Inhibits Na⁺ reabsorption in distal renal tubules, increasing excretion of Na⁺ and water (along with K⁺ and H⁺), reducing blood volume and lowering blood pressure. Long-term use also relaxes blood vessels and improves blood flow.

Adults:
Initial Therapy: One 2.5/6.25 mg tablet once daily.
Titration: Increase at 14-day intervals up to maximum 20/12.5 mg once daily.
Replacement Therapy: May be substituted for titrated individual components.

Renal impairment (CrCl <40 mL/min): Half-life of bisoprolol is increased up to threefold; caution in dosing/titration.

Hepatic impairment: Caution required; dose adjustment may be needed.

Elderly: Dosage adjustment usually not necessary.

Common side effects:
Fatigue, dizziness, headache, bradycardia (slow heart rate), arrhythmia, peripheral ischemia, chest pain, palpitations, cold extremities, claudication, orthostatic hypotension, diarrhea, constipation, nausea, dyspepsia, rhinitis, pharyngitis, increased blood uric acid, decreased potassium level, glucose intolerance, altered blood lipid level, decreased magnesium level, increased calcium level.

Most side effects are mild and transient.

• May cause dizziness; get up slowly from sitting or lying position.
• Do not stop suddenly (withdraw gradually over about 2 weeks).
• Diabetic patients should monitor blood glucose regularly (may mask hypoglycemia symptoms).
• Signs of fluid/electrolyte imbalance (dry mouth, thirst, weakness, lethargy, muscle pain/cramps, hypotension, oliguria, tachycardia, nausea, vomiting) should be reported to your doctor.
• Drink plenty of fluids to prevent dehydration.
• Hyperuricemia or acute gout may occur (due to thiazide diuretic).
• Hypokalemia may develop.
• May affect ability to drive; be cautious.
• Avoid alcohol (may cause excessive drowsiness).
• Regular monitoring of blood pressure, kidney function, blood glucose, potassium, and magnesium levels is recommended.

• Cardiogenic shock
• Uncompensated cardiac failure
• Second or third degree AV block
• Marked sinus bradycardia
• Anuria
• Severe hemorrhage
• Bronchospasm
• Pregnancy
• Hypersensitivity to bisoprolol, hydrochlorothiazide, or other sulfonamide-derived drugs
• Low cardiac output

Bisoprolol:
• Class I antiarrhythmic drugs (quinidine, disopyramide, propafenone) may potentiate AV conduction time and increase negative inotropic effect.
• Catecholamine-depleting drugs (reserpine, guanethidine) may produce excessive sympathetic activity.
• May exacerbate rebound hypertension upon clonidine discontinuation.
• Increased risk of bradycardia with digitalis glycosides.
• Reduced hypotensive effect with NSAIDs.

Hydrochlorothiazide:
• Increases lithium toxicity.
• May potentiate orthostatic hypotension with barbiturates and narcotics.
• Enhances neuromuscular blocking action of competitive neuromuscular blockers (e.g., atracurium).
• Increased hypokalemic effect with corticosteroids, corticotropin, β2 agonists (e.g., salbutamol).
• Additive effect with other antihypertensives.
• Potentiation of orthostatic hypotension with barbiturates or opioids.
• Reduced antihypertensive effect by fluid-retaining drugs (corticosteroids, NSAIDs, carbenoxolone).
• Enhanced nephrotoxicity of NSAIDs.
• Reduced therapeutic effect of antidiabetics.

Beta-blocker overdose: Most frequently observed signs are bradycardia and hypotension. Lethargy is common; severe overdose may cause delirium, coma, convulsions, and respiratory arrest. Congestive heart failure, bronchospasm, and hypoglycemia may occur.

Thiazide diuretic overdose: Acute intoxication is rare. The most prominent feature is acute fluid and electrolyte loss. Signs and symptoms include cardiovascular (tachycardia, hypotension, shock), neuromuscular (weakness, confusion, dizziness, calf muscle cramps, paresthesia, fatigue, impaired consciousness), gastrointestinal (nausea, vomiting, thirst), renal (polyuria, oliguria, or anuria), and laboratory findings (hypokalemia, hyponatremia, hypochloremia, alkalosis, increased BUN especially in renal insufficiency).