This combination tablet is indicated for the treatment of hypertension.

Bisoprolol Fumarate and Hydrochlorothiazide are used both individually and together for managing hypertension. Their combined antihypertensive effect is additive. Hydrochlorothiazide 6.25 mg enhances the blood pressure–lowering effect of Bisoprolol Fumarate. Additionally, the risk of hypokalemia with the combination of Bisoprolol Fumarate and Hydrochlorothiazide 6.25 mg is lower compared to Hydrochlorothiazide 25 mg alone. Bisoprolol Fumarate is a β1-selective (cardioselective) adrenergic receptor blocker that does not exhibit significant membrane-stabilizing or intrinsic sympathomimetic activity at therapeutic doses. Hydrochlorothiazide is a benzothiadiazine diuretic. Thiazide diuretics act on the renal tubules to reduce electrolyte reabsorption, thereby increasing the excretion of sodium and chloride in approximately equal amounts.

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 combination, 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 combination. 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 combination.

This combination may enhance the effects of other antihypertensive medications when used together. It should not be used with other beta-blockers. Patients taking catecholamine-depleting agents (e.g., reserpine or guanethidine) should be closely monitored, as additive beta-blockade may excessively reduce sympathetic activity. When used with clonidine, it is recommended to discontinue this combination several days before stopping clonidine therapy. Caution is required when used with drugs that depress AV conduction, such as certain calcium channel blockers (verapamil, diltiazem) and antiarrhythmic agents (e.g., disopyramide). Concomitant use with digitalis glycosides may further slow AV conduction and reduce heart rate, increasing the risk of bradycardia.

This combination is contraindicated in patients with cardiogenic shock, overt cardiac failure, second- or third-degree AV block, significant sinus bradycardia, anuria, or hypersensitivity to any component of the product or to sulfonamide-derived drugs.

This combination is generally well tolerated, and most side effects are mild and temporary. Reported adverse effects include fatigue, dizziness, headache, bradycardia, arrhythmia, peripheral ischemia, chest pain, palpitations, rhythm disturbances, cold extremities, claudication, orthostatic hypotension, diarrhea, constipation, nausea, dyspepsia, rhinitis, and pharyngitis.

Use in Pregnancy: Classified as Pregnancy Category C. Adequate and well-controlled studies in pregnant women are lacking. This combination should be used during pregnancy only if the expected benefit justifies the potential risk to the fetus.

Use in Nursing Mothers: Bisoprolol Fumarate, alone or in combination with Hydrochlorothiazide, has not been adequately studied in breastfeeding women. Thiazides are excreted into breast milk, and small amounts of bisoprolol have been detected in lactating mothers. Due to the risk of serious adverse effects in nursing infants, a decision should be made to either discontinue breastfeeding or discontinue the drug, considering the importance of the medication to the mother.

Thiazide diuretics may trigger hyperuricemia or acute gout in some patients. Signs of fluid and electrolyte imbalance may include dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain or cramps, fatigue, hypotension, reduced urine output, tachycardia, and gastrointestinal symptoms such as nausea and vomiting. Hypokalemia may also occur. If discontinuation of this combination is required, it should be done gradually over approximately two weeks, and patients should be closely monitored.

Data on overdose with this combination are limited. Overdose of beta-blockers commonly presents with bradycardia and hypotension, along with lethargy. In severe cases, symptoms such as delirium, coma, convulsions, and respiratory arrest may occur. Congestive heart failure, bronchospasm, and hypoglycemia are also possible. With thiazide diuretics, acute toxicity is rare, but overdose may lead to significant fluid and electrolyte loss. Clinical features may include cardiovascular symptoms (tachycardia, hypotension, shock), neurological symptoms (weakness, confusion, dizziness, muscle cramps, paresthesia, fatigue, impaired consciousness), gastrointestinal symptoms (nausea, vomiting, thirst), renal impairment (polyuria, oliguria, or anuria), and laboratory abnormalities such as hypokalemia, hyponatremia, hypochloremia, alkalosis, and elevated blood urea nitrogen (BUN), especially in patients with renal dysfunction.

Combined antihypertensive preparations

Store below 30°C, protected from light and moisture. Keep out of reach of children.