Find Medicines

This topical preparation is indicated for the topical treatment of inflammatory dermal infections like-

• Tinea pedis
• Tinea cruris
• Tinea corporis etc.

Betamethasone & Combined preparations

Clotrimazole is a broad-spectrum antifungal agent used for the treatment of superficial infections caused by species of pathogenic dermatophytes, yeasts and Malassezia furfur. The mechanism of action involves inhibition of the synthesis of ergosterol, a major sterol in the fungal cell membrane. This leads to instability of the cell membrane and eventual death of the fungus. Betamethasone dipropionate is a corticosteroid with anti-inflammatory, antipruritic, and vasoconstrictive properties. But the exact mechanism of action of corticosteroids is not clearly known.

Sufficient topical preparation should be applied onto the affected and surrounding skin areas twice a day, in the morning and evening, for 2 weeks in tinea cruris and tinea corporis and for 4 weeks in tinea pedis. The use of this cream for longer than four weeks is not recommended.

The safety and effectiveness of the preparation have not been established in children below the age of 12 years.

Adverse reactions reported for the preparation in clinical trials were paresthesia in 1.9% of patients, rash, edema and secondary infection, each in less than 1% of patients. Other adverse reactions reported with the preparation were burning and dry skin in 1.6% of patients and stinging in less than 1% of patients

This topical preparation is contraindicated to those patients who are sensitive to any of its components or to other corticosteroids or to imidazoles. If irritation or sensitization develops with the use of the cream, treatment should be discontinued and appropriate therapy instituted. The cream is contraindicated in facial rosacea, acne vulgaris, perioral dermatits, perianal and genital pruritus, napkin eruptions and bacterial or viral infections. Systemic absorption of topical corticosteroides can produce reversible hypothalmic-pituitary-adrenal (HPA) axis suppression. If HPA axis suppression is noted, an attempt should be made to withdraw the drug or to reduce the frequency of application. Pediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their large skin surface to body mass ratios.

No information is available of drug interaction.

There is inadequate evidence of safety in pregnancy. Clotrimazole has no teratogenic effect in animals but is foetotoxic at high oral doses. Topical administration of corticosteroids to pregnant animals can cause abnormalities of fetal development. Hence the cream should only be used in pregnancy if the benefit justifies the potential risk to the fetus and such use should not be extensive,i.e. in large amounts or for long periods. It is not known whether the components of the preparation are excreted in human milk and therefore caution should be exercised when treating nursing mothers.

Acute overdose with the cream is unlikely and would not be expected to lead to a life-threatening situation. The cream should not be used for longer than the prescribed time period.

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

Bisoprolol is indicated in-

• Hypertension
• Angina
• Moderate to severe heart failure

Bisoprolol is not recommended for the emergency treatment of hypertensive crises.

Anti adrenergic agent (Beta blockers), Beta-adrenoceptor blocking drugs, Beta-blockers

Bisoprolol Hemifumarate is the most selective ß1 blocker. It displays highest level of affinity for the ß1 receptor than any other beta-blocker available up to now. Selectively blocks ß1 adrenergic receptor in the heart and vascular smooth muscle and reduces heart rate and cardiac output resulting in decrease of arterial hypertension. Lipid metabolism can be adversely affected by ß-blockers, in patients with non-ß1 selective ß1-blocker, but Bisoprolol does not cause any change in the cholesterol fraction including the cardioprotective HDL-cholesterol, in long-term therapy.

Adult: In the treatment of mild to moderate hypertension, Bisoprolol fumarate must be individualized to the needs of the patient. The usual starting dose is 5 mg once daily either added to a diuretic or alone. If the response to 5 mg is inadequate, the dose may be increased to 10 mg and then, if necessary, to 20 mg once daily. An appropriate interval for dose titration is 2 weeks. Increasing the dose beyond 20 mg once daily produces only a small incremental benefit.

Children: Safety and effectiveness in children have not been established.

Patients With Renal or Hepatic Impairment: In patients with hepatic impairment (hepatitis or cirrhosis) or renal dysfunction (creatinine clearance less than 40 mL/min) as in other patients, the initial daily dose should be 5 mg. Because of the possibility of accumulation, caution must be used in dose titration. Since limited data suggest that bisoprolol fumarate is not dialysable, drug replacement is not necessary in patients undergoing dialysis.

Geriatrics: In the elderly, it is not usually necessary to adjust the dose, unless there is also significant renal or hepatic dysfunction

Bisoprolol, like any medication, may have some side effects. It is important that you keep your doctor informed of all side effects especially if you experience one of the following for several days. The most common side effects, whether or not caused by Bisoprolol, are: headache, fatigue, urinary tract infection, rhinitis or sinusitis (inflammation in the nose), diarrhea, dizziness, peripheral edema (swelling of the ankles), joint pain, cough, insomnia (trouble sleeping), nausea (feeling like vomiting), and sore throat. You must seek medical attention immediately if you experience an allergic reaction with symptoms of rash, itching, swelling, dizziness or trouble breathing.

Medicines affect different people in different ways. Just because side effects have occurred in other patients does not mean you will get them. Discuss how you feel on Bisoprolol with your doctor or pharmacist. Do not stop or restart Bisoprolol on your own.

In patients with cardiogenic shock, overt heart failure, second or third degree A-V block, right ventricular failure secondary to pulmonary hypertension and sinus bradycardia.

Monitoring of renal, hepatic and hematopoietic function should be performed at regular intervals during long-term treatment with bisoprolol.

Other β-blocking Agents: Bisoprolol fumarate should not be combined with other β-blocking agents.

Catecholamine-Depleting Drugs: Patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, should be monitored closely because the added β-adrenergic blocking action of bisoprolol fumarate may produce excessive reduction of sympathetic activity.

Centrally Active Antihypertensive Agents: β-blockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are coadministered, the β-blocker should be withdrawn several days before discontinuing clonidine. If replacing clonidine by β-blocker therapy, the introduction of β-blockers should be delayed for several days after clonidine administration has stopped (see also prescribing information for clonidine).

Antiarrhythmic Agents: Bisoprolol fumarate should be used with care when myocardial depressants or inhibitors of A-V conduction, such as certain calcium antagonists (particularly of the phenyl alkylamine (verapamil) and benzothiazepine (diltiazem) classes), or antiarrhythmic agents, such as disopyramide, are used concurrently.

Calcium Channel Blockers: Combined use of β-blockers and calcium channel blockers with negative inotropic effects can lead to prolongation of S-A and A-V conduction, particularly in patients with impaired ventricular function or conduction abnormalities. This may result in severe hypotension, bradycardia and cardiac failure.

Pregnancy: Bisoprolol fumarate was not teratogenic in rats at doses up to 150 mg/kg/day, which is 375 times the maximum recommended human daily dose. Bisoprolol fumarate was fetotoxic (increased late resorptions) at 50 mg/kg/day and maternotoxic (decreased food intake and body-weight gain) at 150 mg/kg/day. Bisoprolol fumarate was not teratogenic in rabbits at doses up to 12.5 mg/kg/day, which is 31 times the maximum recommended human daily dose, but was embryolethal (increased early resorptions) at 12.5 mg/kg/day. There are no studies in pregnant women. Bisoprolol fumarate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: Small amounts of bisoprolol fumarate (<2% of the dose) have been detected in the milk of lactating rats. It is not known whether this drug is excreted in human milk. If use of bisoprolol fumarate is considered essential, then mothers should stop nursing.

Keep in a dry place away from light and heat. Keep out of the reach of children.

Bisoprolol is indicated in-

• Hypertension
• Angina
• Moderate to severe heart failure

Bisoprolol is not recommended for the emergency treatment of hypertensive crises.

Anti adrenergic agent (Beta blockers), Beta-adrenoceptor blocking drugs, Beta-blockers

Bisoprolol Hemifumarate is the most selective ß1 blocker. It displays highest level of affinity for the ß1 receptor than any other beta-blocker available up to now. Selectively blocks ß1 adrenergic receptor in the heart and vascular smooth muscle and reduces heart rate and cardiac output resulting in decrease of arterial hypertension. Lipid metabolism can be adversely affected by ß-blockers, in patients with non-ß1 selective ß1-blocker, but Bisoprolol does not cause any change in the cholesterol fraction including the cardioprotective HDL-cholesterol, in long-term therapy.

Adult: In the treatment of mild to moderate hypertension, Bisoprolol fumarate must be individualized to the needs of the patient. The usual starting dose is 5 mg once daily either added to a diuretic or alone. If the response to 5 mg is inadequate, the dose may be increased to 10 mg and then, if necessary, to 20 mg once daily. An appropriate interval for dose titration is 2 weeks. Increasing the dose beyond 20 mg once daily produces only a small incremental benefit.

Children: Safety and effectiveness in children have not been established.

Patients With Renal or Hepatic Impairment: In patients with hepatic impairment (hepatitis or cirrhosis) or renal dysfunction (creatinine clearance less than 40 mL/min) as in other patients, the initial daily dose should be 5 mg. Because of the possibility of accumulation, caution must be used in dose titration. Since limited data suggest that bisoprolol fumarate is not dialysable, drug replacement is not necessary in patients undergoing dialysis.

Geriatrics: In the elderly, it is not usually necessary to adjust the dose, unless there is also significant renal or hepatic dysfunction

Bisoprolol, like any medication, may have some side effects. It is important that you keep your doctor informed of all side effects especially if you experience one of the following for several days. The most common side effects, whether or not caused by Bisoprolol, are: headache, fatigue, urinary tract infection, rhinitis or sinusitis (inflammation in the nose), diarrhea, dizziness, peripheral edema (swelling of the ankles), joint pain, cough, insomnia (trouble sleeping), nausea (feeling like vomiting), and sore throat. You must seek medical attention immediately if you experience an allergic reaction with symptoms of rash, itching, swelling, dizziness or trouble breathing.

Medicines affect different people in different ways. Just because side effects have occurred in other patients does not mean you will get them. Discuss how you feel on Bisoprolol with your doctor or pharmacist. Do not stop or restart Bisoprolol on your own.

In patients with cardiogenic shock, overt heart failure, second or third degree A-V block, right ventricular failure secondary to pulmonary hypertension and sinus bradycardia.

Monitoring of renal, hepatic and hematopoietic function should be performed at regular intervals during long-term treatment with bisoprolol.

Other β-blocking Agents: Bisoprolol fumarate should not be combined with other β-blocking agents.

Catecholamine-Depleting Drugs: Patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, should be monitored closely because the added β-adrenergic blocking action of bisoprolol fumarate may produce excessive reduction of sympathetic activity.

Centrally Active Antihypertensive Agents: β-blockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are coadministered, the β-blocker should be withdrawn several days before discontinuing clonidine. If replacing clonidine by β-blocker therapy, the introduction of β-blockers should be delayed for several days after clonidine administration has stopped (see also prescribing information for clonidine).

Antiarrhythmic Agents: Bisoprolol fumarate should be used with care when myocardial depressants or inhibitors of A-V conduction, such as certain calcium antagonists (particularly of the phenyl alkylamine (verapamil) and benzothiazepine (diltiazem) classes), or antiarrhythmic agents, such as disopyramide, are used concurrently.

Calcium Channel Blockers: Combined use of β-blockers and calcium channel blockers with negative inotropic effects can lead to prolongation of S-A and A-V conduction, particularly in patients with impaired ventricular function or conduction abnormalities. This may result in severe hypotension, bradycardia and cardiac failure.

Pregnancy: Bisoprolol fumarate was not teratogenic in rats at doses up to 150 mg/kg/day, which is 375 times the maximum recommended human daily dose. Bisoprolol fumarate was fetotoxic (increased late resorptions) at 50 mg/kg/day and maternotoxic (decreased food intake and body-weight gain) at 150 mg/kg/day. Bisoprolol fumarate was not teratogenic in rabbits at doses up to 12.5 mg/kg/day, which is 31 times the maximum recommended human daily dose, but was embryolethal (increased early resorptions) at 12.5 mg/kg/day. There are no studies in pregnant women. Bisoprolol fumarate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: Small amounts of bisoprolol fumarate (<2% of the dose) have been detected in the milk of lactating rats. It is not known whether this drug is excreted in human milk. If use of bisoprolol fumarate is considered essential, then mothers should stop nursing.

Keep in a dry place away from light and heat. Keep out of the reach of children.

Bisoprolol is indicated in-

• Hypertension
• Angina
• Moderate to severe heart failure

Bisoprolol is not recommended for the emergency treatment of hypertensive crises.

Anti adrenergic agent (Beta blockers), Beta-adrenoceptor blocking drugs, Beta-blockers

Bisoprolol Hemifumarate is the most selective ß1 blocker. It displays highest level of affinity for the ß1 receptor than any other beta-blocker available up to now. Selectively blocks ß1 adrenergic receptor in the heart and vascular smooth muscle and reduces heart rate and cardiac output resulting in decrease of arterial hypertension. Lipid metabolism can be adversely affected by ß-blockers, in patients with non-ß1 selective ß1-blocker, but Bisoprolol does not cause any change in the cholesterol fraction including the cardioprotective HDL-cholesterol, in long-term therapy.

Adult: In the treatment of mild to moderate hypertension, Bisoprolol fumarate must be individualized to the needs of the patient. The usual starting dose is 5 mg once daily either added to a diuretic or alone. If the response to 5 mg is inadequate, the dose may be increased to 10 mg and then, if necessary, to 20 mg once daily. An appropriate interval for dose titration is 2 weeks. Increasing the dose beyond 20 mg once daily produces only a small incremental benefit.

Children: Safety and effectiveness in children have not been established.

Patients With Renal or Hepatic Impairment: In patients with hepatic impairment (hepatitis or cirrhosis) or renal dysfunction (creatinine clearance less than 40 mL/min) as in other patients, the initial daily dose should be 5 mg. Because of the possibility of accumulation, caution must be used in dose titration. Since limited data suggest that bisoprolol fumarate is not dialysable, drug replacement is not necessary in patients undergoing dialysis.

Geriatrics: In the elderly, it is not usually necessary to adjust the dose, unless there is also significant renal or hepatic dysfunction

Bisoprolol, like any medication, may have some side effects. It is important that you keep your doctor informed of all side effects especially if you experience one of the following for several days. The most common side effects, whether or not caused by Bisoprolol, are: headache, fatigue, urinary tract infection, rhinitis or sinusitis (inflammation in the nose), diarrhea, dizziness, peripheral edema (swelling of the ankles), joint pain, cough, insomnia (trouble sleeping), nausea (feeling like vomiting), and sore throat. You must seek medical attention immediately if you experience an allergic reaction with symptoms of rash, itching, swelling, dizziness or trouble breathing.

Medicines affect different people in different ways. Just because side effects have occurred in other patients does not mean you will get them. Discuss how you feel on Bisoprolol with your doctor or pharmacist. Do not stop or restart Bisoprolol on your own.

In patients with cardiogenic shock, overt heart failure, second or third degree A-V block, right ventricular failure secondary to pulmonary hypertension and sinus bradycardia.

Monitoring of renal, hepatic and hematopoietic function should be performed at regular intervals during long-term treatment with bisoprolol.

Other β-blocking Agents: Bisoprolol fumarate should not be combined with other β-blocking agents.

Catecholamine-Depleting Drugs: Patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, should be monitored closely because the added β-adrenergic blocking action of bisoprolol fumarate may produce excessive reduction of sympathetic activity.

Centrally Active Antihypertensive Agents: β-blockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are coadministered, the β-blocker should be withdrawn several days before discontinuing clonidine. If replacing clonidine by β-blocker therapy, the introduction of β-blockers should be delayed for several days after clonidine administration has stopped (see also prescribing information for clonidine).

Antiarrhythmic Agents: Bisoprolol fumarate should be used with care when myocardial depressants or inhibitors of A-V conduction, such as certain calcium antagonists (particularly of the phenyl alkylamine (verapamil) and benzothiazepine (diltiazem) classes), or antiarrhythmic agents, such as disopyramide, are used concurrently.

Calcium Channel Blockers: Combined use of β-blockers and calcium channel blockers with negative inotropic effects can lead to prolongation of S-A and A-V conduction, particularly in patients with impaired ventricular function or conduction abnormalities. This may result in severe hypotension, bradycardia and cardiac failure.

Pregnancy: Bisoprolol fumarate was not teratogenic in rats at doses up to 150 mg/kg/day, which is 375 times the maximum recommended human daily dose. Bisoprolol fumarate was fetotoxic (increased late resorptions) at 50 mg/kg/day and maternotoxic (decreased food intake and body-weight gain) at 150 mg/kg/day. Bisoprolol fumarate was not teratogenic in rabbits at doses up to 12.5 mg/kg/day, which is 31 times the maximum recommended human daily dose, but was embryolethal (increased early resorptions) at 12.5 mg/kg/day. There are no studies in pregnant women. Bisoprolol fumarate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: Small amounts of bisoprolol fumarate (<2% of the dose) have been detected in the milk of lactating rats. It is not known whether this drug is excreted in human milk. If use of bisoprolol fumarate is considered essential, then mothers should stop nursing.

Keep in a dry place away from light and heat. Keep out of the reach of children.

Bisoprolol plus Hydrochlorothiazide is indicated in the treatment of Hypertension.

Combined antihypertensive preparations

Bisoprolol Fumarate and Hydrochlorothiazide have been used individually and in combination for the treatment of hypertension. The antihypertensive effects of these agents are additive; Hydrochlorothiazide 6.25 mg significantly increases the antihypertensive effect of Bisoprolol Fumarate. The incidence of hypokalemia with the Bisoprolol Fumarate and Hydrochlorothiazide 6.25 mg combination is significantly lower than with Hydrochlorothiazide 25 mg. Bisoprolol Fumarate is a β1-selective (cardioselective) adrenoceptor blocking agent without significant membrane stabilizing or intrinsic sympathomimetic activities in its therapeutic dose range. Hydrochlorothiazide is a benzothiadiazine diuretic. Thiazides affect renal tubular mechanisms of electrolyte reabsorption and increase excretion of sodium and chloride in approximately equivalent 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 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.

Generally well tolerated. Most side effects have been mild and transient. Side effects which may occur: fatigue, dizziness, headache, bradycardia, arrhythmia, peripheral ischemia, chest pain, palpitations, rhythm disturbances, cold extremities, claudication, orthostatic hypotension, diarrhoea, constipation, nausea, dyspepsia, rhinitis, pharyngitis etc.

It is contraindicated in patients in cardiogenic shock, overt cardiac failure, second or third degree AV block, marked sinus bradycardia, anuria and hypersensitivity to either component of this product or to other sulfonamide-derived drugs.

Hyperuricemia or acute gout may be precipitated in certain patients receiving thiazide diuretics. Warning signs or symptoms of fluid and electrolyte imbalance include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia and gastrointestinal disturbances such as nausea and vomiting. Hypokalemia may develop. If withdrawal of this combination therapy is planned, it should be achieved gradually over a period of about 2 weeks. Patients should be carefully observed.

This combination drug may potentiate the action of other antihypertensive agents used concomitantly. This combination drug should not be combined with other beta-blocking agents. Patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, should be closely monitored because the added beta-adrenergic blocking action of Bisoprolol Fumarate may produce excessive reduction of sympathetic activity. In patients receiving concurrent therapy with clonidine, if therapy is to be discontinued, it is suggested that this combination drug be discontinued for several days before the withdrawal of clonidine. This combination drug should be used with caution when myocardial depressants or inhibitors of AV conduction, such as certain calcium antagonists (particularly of the phenylalkylamine [verapamil] and benzothiazepine [diltiazem] classes) or antiarrhythmic agents, such as disopyramide, are used concurrently. Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Use in Pregnancy: Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Bisoprolol Fumarate and Hydrochlorothiazide should be used during pregnancy only if the potential benefit justifies the risk to the fetus.

Use in Nursing Mothers: Bisoprolol Fumarate alone or in combination with Hydrochlorothiazide has not been studied in nursing mothers. Thiazides are excreted in human breast milk. Small amounts of Bisoprolol Fumarate have been detected in the milk of lactating rats. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

There are limited data on overdose with this combination product. The most frequently observed signs expected with overdosage of a beta-blocker are bradycardia and hypotension. Lethargy is also common and with severe overdoses, delirium, coma, convulsions, and respiratory arrest have been reported to occur. Congestive heart failure, bronchospasm, and hypoglycemia may occur. With thiazide diuretics, acute intoxication is rare. The most prominent feature of overdose is acute loss of fluid and electrolytes. Signs and symptoms include cardiovascular (tachycardia, hypotension, shock), neuromuscular (weakness, confusion, dizziness, cramps of the calf muscles, paresthesia, fatigue, impairment of consciousness), gastrointestinal (nausea, vomiting, thirst), renal (polyuria, oliguria, or anuria), and laboratory findings (hypokalemia, hyponatremia, hypochloremia, alkalosis, increased BUN [especially in patients with renal insufficiency]).

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

Bisoprolol plus Hydrochlorothiazide is indicated in the treatment of Hypertension.

Combined antihypertensive preparations

Bisoprolol Fumarate and Hydrochlorothiazide have been used individually and in combination for the treatment of hypertension. The antihypertensive effects of these agents are additive; Hydrochlorothiazide 6.25 mg significantly increases the antihypertensive effect of Bisoprolol Fumarate. The incidence of hypokalemia with the Bisoprolol Fumarate and Hydrochlorothiazide 6.25 mg combination is significantly lower than with Hydrochlorothiazide 25 mg. Bisoprolol Fumarate is a β1-selective (cardioselective) adrenoceptor blocking agent without significant membrane stabilizing or intrinsic sympathomimetic activities in its therapeutic dose range. Hydrochlorothiazide is a benzothiadiazine diuretic. Thiazides affect renal tubular mechanisms of electrolyte reabsorption and increase excretion of sodium and chloride in approximately equivalent 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 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.

Generally well tolerated. Most side effects have been mild and transient. Side effects which may occur: fatigue, dizziness, headache, bradycardia, arrhythmia, peripheral ischemia, chest pain, palpitations, rhythm disturbances, cold extremities, claudication, orthostatic hypotension, diarrhoea, constipation, nausea, dyspepsia, rhinitis, pharyngitis etc.

It is contraindicated in patients in cardiogenic shock, overt cardiac failure, second or third degree AV block, marked sinus bradycardia, anuria and hypersensitivity to either component of this product or to other sulfonamide-derived drugs.

Hyperuricemia or acute gout may be precipitated in certain patients receiving thiazide diuretics. Warning signs or symptoms of fluid and electrolyte imbalance include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia and gastrointestinal disturbances such as nausea and vomiting. Hypokalemia may develop. If withdrawal of this combination therapy is planned, it should be achieved gradually over a period of about 2 weeks. Patients should be carefully observed.

This combination drug may potentiate the action of other antihypertensive agents used concomitantly. This combination drug should not be combined with other beta-blocking agents. Patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, should be closely monitored because the added beta-adrenergic blocking action of Bisoprolol Fumarate may produce excessive reduction of sympathetic activity. In patients receiving concurrent therapy with clonidine, if therapy is to be discontinued, it is suggested that this combination drug be discontinued for several days before the withdrawal of clonidine. This combination drug should be used with caution when myocardial depressants or inhibitors of AV conduction, such as certain calcium antagonists (particularly of the phenylalkylamine [verapamil] and benzothiazepine [diltiazem] classes) or antiarrhythmic agents, such as disopyramide, are used concurrently. Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Use in Pregnancy: Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Bisoprolol Fumarate and Hydrochlorothiazide should be used during pregnancy only if the potential benefit justifies the risk to the fetus.

Use in Nursing Mothers: Bisoprolol Fumarate alone or in combination with Hydrochlorothiazide has not been studied in nursing mothers. Thiazides are excreted in human breast milk. Small amounts of Bisoprolol Fumarate have been detected in the milk of lactating rats. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

There are limited data on overdose with this combination product. The most frequently observed signs expected with overdosage of a beta-blocker are bradycardia and hypotension. Lethargy is also common and with severe overdoses, delirium, coma, convulsions, and respiratory arrest have been reported to occur. Congestive heart failure, bronchospasm, and hypoglycemia may occur. With thiazide diuretics, acute intoxication is rare. The most prominent feature of overdose is acute loss of fluid and electrolytes. Signs and symptoms include cardiovascular (tachycardia, hypotension, shock), neuromuscular (weakness, confusion, dizziness, cramps of the calf muscles, paresthesia, fatigue, impairment of consciousness), gastrointestinal (nausea, vomiting, thirst), renal (polyuria, oliguria, or anuria), and laboratory findings (hypokalemia, hyponatremia, hypochloremia, alkalosis, increased BUN [especially in patients with renal insufficiency]).

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

Bisoprolol & Amlodipine combination is indicated for the treatment of hypertension as substitution therapy in patients adequately controlled with the individual products given concurrently at the same dose level as in the combination, but as separate tablets

Anti-hypertensive

This consists of Amlodipine and Bisoprolol Fumarate. Amlodipine is a dihydropyridine calcium antagonist that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Amlodipine acts directly on vessels to cause a reduction in peripheral vascular resistance and reduction in blood pressure.

Bisoprolol Fumarate is a synthetic, beta1-selective (cardioselective) adrenoceptor blocking agent, lacking intrinsic sympathomimetic and relevant membrane stabilizing activity. It only shows low affinity to the beta2 receptor of the smooth muscles of bronchi and vessels as well as to the beta2-receptors concerned with metabolic regulation. Therefore, bisoprolol is generally not to be expected to influence airway resistance and beta2-mediated metabolic effects. Its beta1-selectivity extends beyond the therapeutic dose range.

One tablet once daily in patients whose blood pressure is adequately controlled with separately administered monocomponent products of the same doses as the recommended fixed-dose combination.

Common: Dizziness, headache, somnolence, palpitations, flushing, feeling of coldness or numbness in the extremities, gastrointestinal complaints such as nausea, vomiting, diarrhea, constipation, abdominal pain; edema (e.g. ankle edema), fatigue.

Uncommon: Insomnia, mood changes (incl. anxiety), depression, sleep disorders, hypaesthesia, paresthesia, dysgeusia, tremor, visual disturbances (incl. diplopia), tinnitus, AV conduction disturbances, worsening of pre existing heart failure, bradycardia, hypotension, syncope, dyspnea, bronchospasm in patients with bronchial asthma or a history of obstructive airway disease, rhinitis, dyspepsia, dry mouth, alopecia, purpura, skin discoloration, pruritus, exanthema, arthralgia, myalgia, muscular weakness, muscle cramps, back pain, micturition disorder, nocturia, pollakisuria, potency disorders, gynecomastia, asthenia, chest pain, pain, malaise, weight increase, weight decrease.

Rare: Allergic reactions mainly affecting the skin, nightmares, hallucinations, confusion, decreased tear secretion, hearing disorders, allergic rhinitis, hepatitis, increased triglycerides, increased liver enzymes (ALAT, ASAT).

Acute heart failure or during episodes of heart failure decompensation, obstruction of the outflow tract of the left ventricle (e.g. high grade aortic stenosis), cardiogenic shock, second or third degree AV block, sick sinus syndrome, sinoatrial block, symptomatic bradycardia or hypotension, severe bronchial asthma, severe forms of peripheral arterial occlusive disease or severe forms of Raynaud’s syndrome, untreated phaeochromocytoma metabolic acidosis, hypersensitivity to bisoprolol, amlodipine, dihydropyridine derivates or to any of the excipients.

Patients with heart failure should be treated with caution. An increased risk of a further deterioration of the ventricular pump function cannot be excluded. Since the abrupt withdrawal of bisoprolol may lead to a transitory worsening of the clinical condition, especially in patients with ischemic heart disease, the treatment must not be stopped abruptly. Caution is advised in patients with impaired hepatic function. Beta-blockers should be avoided in patients with obstructive airways diseases unless there are compelling clinical reasons for their use. Due to the bisoprolol component treatment must be used with caution in: bronchospasm (bronchial asthma, chronic obstructive airways disease; concomitant bronchodilating therapy may be recommended); diabetes mellitus showing large fluctuations in blood glucose values, symptoms of hypoglycemia can be masked; strict fasting; ongoing desensitization therapy; first degree AV block; Prinzmetal’s angina; peripheral arterial occlusive disease. Patients with psoriasis or with a history of psoriasis should only be given beta-blockers (e.g. bisoprolol) after a careful balancing of benefits and risks. Symptoms of thyrotoxicosis may be masked. In patients undergoing general anesthesia, the anesthetist must be aware of beta-blockade. If it is thought necessary to withdraw beta blocker therapy before surgery, this should be done gradually and completed about 48 hours before anesthesia.

Combinations not recommended: Calcium antagonists of the verapamil and diltiazem type, centrally-acting antihypertensive drugs.

Combinations to be used with caution: Strong or moderate CYP3A4 inhibitors, CYP3A4 inducers, simvastatin, Tacrolimus, Cyclosporine, class I antiarrhythmic drugs, class III antiarrhythmic drugs, parasympathomimetic drugs, topical beta-blockers (e.g. eye drops), insulin and oral antidiabetic drugs, anesthetic agents, digitalis glycosides, non-steroidal anti-inflammatory drugs (NSAIDs), sympathomimetic agents, antihypertensive agents and other drugs with blood pressure lowering potential.

Combinations to be considered: Mefloquine, Rifampicin, Ergotamine derivatives, MAO inhibitors (except MAO-B inhibitor).

Pregnancy and Lactation: Not recommended.

Geriatric use: The usual doses can be administered to elderly people; however, caution is advised when the dose is increased.

Pediatric use: The safety and efficacy of Bisoprolol fumarate/amlodipine in children and adolescents below the age of 18 years have not been established. No data are available.

Patients with Liver disease: In case of hepatic impairment elimination of amlodipine may be elongated. Exact dosage recommendations concerning amlodipine have not been established, but the drug should therefore be administered with special caution in these patients. In case of severe hepatic impairment, the daily dose of bisoprolol must not exceed 10 mg.

Patients with Kidney disease: No dosage adjustment is required for patients with mild to moderate renal impairment. Amlodipine is not dialyzable. Amlodipine should be administered with particular caution to patients undergoing dialysis. In case of severe renal impairment (creatinine clearance <20 ml/min) the daily dose of bisoprolol must not exceed 10 mg

Most common signs expected with overdose of a beta-blocker are bradycardia, hypotension, bronchospasm, acute cardiac insufficiency, hypoglycemia. According to available data gross overdose of amlodipine could result in excessive peripheral vasodilation and possibly reflex tachycardia. Marked and probably prolonged systemic hypotension up to and including shock with fatal outcome have been reported. In general, if overdose occurs, discontinuation of treatment and supportive and symptomatic treatment is recommended.

Keep in a dry place, below 30°C. Protect from light. Keep out of the reach of children.

β-Sitosterol has been used successfully in the treatment of the following wounds:

• Burn
• Leg ulcer
• Surgical wound
• Obstetric wound
• Cracked nipple

Herbal and Nutraceuticals

A thin layer of β-Sitosterol ointment should be applied to the whole burn/affected area 3-4 times daily.

No side effects to the product have been reported so far except for rare allergic reactions to sesame oil.

Avoid contact with eyes or mucous membrane. Avoid accidental ingestion. If swallowed, get medical treatment. β-Sitosterol ointment may vary its physical appearance during storage, especially during the hot season. But it does not lose its effcacy.

Store in a cool & dry place, below 30°C. Protect from direct sunlight & moisture. Keep the medicine out of the reach of children.

This is indicated in-

• Patients with essential hypertension
• Patients with angina pectoris & hypertension as co-existing diseases
• ln post Ml patients
• ln patients with refractory angina pectoris where nitrate therapy has failed.

Combined antihypertensive preparations

This is a fixed-dose combination of Amlodipine and Atenolol. Amlodipine is a dihydropyridine calcium antagonist that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle; it has a greater effect on vascular smooth muscle than on cardiac muscle. Amlodipine is a peripheral vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure. Amlodipine reduces tone, decreases coronary vasoreactivity and lowers cardiac demand by reducing afterload.

Atenolol is a cardioselective beta-blocker. The cardio-selectivity is dose-related. Atenolol causes a reduction in blood pressure by lowering cardiac output, decreasing the plasma renin activity and sympathetic outflow from CNS. Atenolol also causes a reduction in myocardial oxygen demand by virtue of its negative inotropic and negative chronotropic effects.

The recommended dosage is Amlodipine and Atenolol 5/25 mg tablet once daily. If necessary, the dosage may be increased to 5/25 mg two tablets daily or as advised by the physicians. The dosage however should be individualized.

The combination of Amlodipine and Atenolol is well tolerated. Overall side-effects include
fatigue, headache, edema, nausea, drowsiness, anxiety and depression.

Hypersensitivity to either component, sinus bradycardia, second and higher degrees of heart block, cardiogenic shock, hypotension, congestive heart failure, poor left ventricular function.

Bronchospasm: The combination should be used with caution in patients with airway obstruction.

Renal impairment: The combination can be used in patients with renal impairment. However, caution may be necessary if the creatinine clearance is less than 30 ml/min because of possible reduction in the excretion of unchanged Atenolol.

Hepatic impairment: Caution may be necessary in the use of the combination in patients with severe liver damage because of prolongation of the elimination half-life of Amlodipine.

Drug withdrawal: Since coronary heart disease may exist without being recognized, patients should be warned against stopping the drug suddenly. Any discontinuation should be gradual and under observation.

Disopyramide: Atenolol reduces the clearance of disopyramide by 20%. Additive negative inotropic effects on the heart may be produced.

Ampicillin: at doses of 1 gm and above may reduce Atenolol levels.

Oral antidiabetics and insulin: Beta-blockers may decrease tissue sensitivity to insulin and inhibit insulin secretion e.g. in response to oral antidiabetics. Atenolol has less potential for these actions.

The combination should be used during pregnancy only if the expected benefit outweighs the potential fetal risk. The combination should not be used by nursing mothers. If its use is considered necessary, breast-feeding should be stopped.

Though not documented, hypotension and less frequently congestive cardiac failure may occur in cases of overdosage. Unabsorbed drugs may be removed by gastric lavage or administration of activated charcoal. Symptomatic treatment is suggested.

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

Propranolol is indicated in:

• Essential hypertension
• Angina pectoris
• Cardiac arrhythmia
• Thyrotoxicosis
• Anxiety
• Prophylaxis of migraine, etc.

Beta-adrenoceptor blocking drugs, Beta-blockers

Propranolol Hydrochloride is a B-adrenergic receptor blocking drug which is widely used in hypertension and angina pectoris. Propranolol antagonizes catecholamines at B-adrenergic receptors, thus prevents excess rate and force of contraction of the heart and decreases the excess consumption of oxygen by the heart.

Propranolol is almost completely absorbed from the gastrointestinal tract, but a portion is immediately metabolized by the liver when passing through the portal circulation. Peak plasma concentration occurs in 1 to 1.5 hours after oral administration. The plasma half-life of propranolol is from 3 to 6 hours. The metabolites of propranolol are excreted through the urine.

Adult (above 18 years):

• Hypertension: Initially 80 mg twice daily, may be increased at weekly intervals and then maintenance dose of 160-320 mg daily is recommended.
• Angina pectoris: Initially 40 mg 2-3 times daily and then maintenance dose of 120-240 mg daily is given.
• Thyrotoxicosis: 10-40 mg, 3-4 times daily is given.
• Anxiety: 40 mg once daily, may be increased to three times daily.
• Prophylaxis of migraine: Initially 40 mg 2-3 times daily; then maintenance dose of 80-160 mg daily is recommended.

Child (From day 1 to 18 years): Hypertension:

• Neonate: 0.25-0.5 mg/kg 3 times daily, adjusted according to response.
• Child 1 month: 12 years: 0.25-1 mg/kg 3 times daily, maximum dose 5 mg/kg daily in divided dose.
• Child 12-18 years: initially 80 mg twice daily, maintain 160-320 mg daily.

Cold extremities, lassitude, nausea, dizziness, insomnia, paresthesia etc.

Bronchospasm, cardiogenic shock, second or third degree heart block, diabetes mellitus etc.

It should be taken with caution in hepatic and renal impairment, pregnancy and lactating mother.

Patients receiving verapamil, salbutamol, Levosalbutamol, ergot alkaloids, lidocain, phenobarbital drugs should be closely observed during therapy.

Pregnancy category C, should not be used in pregnant women. Propranolol is excreted in human milk. Caution should be taken when propranolol is administered to a nursing mother.

Store in a cool and dry place, protected from light.

Metoprolol is a selective beta1-blocker. Metoprolol reduces or inhibits the agonistic effect on the heart of catecholamines (which are released during physical and mental stress). This means that the usual increase in heart rate, cardiac output, cardiac contractility and blood pressure, produced by the acute increase in catecholamines, is reduced by Metoprolol. Metoprolol interferes less with Insulin release and carbohydrate metabolism than do non-selective beta-blockers. Metoprolol interferes much less with the cardiovascular response to hypoglycaemia than do non-selective beta-blockers.

Film-coated tablet-

• Hypertension: Total daily dosage Metoprolol 100-400 mg to be given as a single or twice-daily dose. The starting dose is 100 mg (two Metoprolol-50 tablets) per day. This may be increased by 100 mg per day at weekly intervals. lf full control is not achieved using a single daily dose, a b.i.d. regimen should be initiated. Combination therapy with a diuretic or other antihypertensive agents may also be considered.
• Angina: Usually Metoprolol 50 mg (one Metoprolol-50 tablet) to 100 mg (two Metoprolol-50 tablets) twice or three times daily.
• Cardiac arrhythmias: Metoprolol 50 mg (one Metoprolol-50 tablet) b.i.d or t.i.d should usually control the condition. It is necessary the dose can be increased up to 300 mg per day in divided doses. Following the treatment of an acute arrhythmia with Metoprolol injection, continuation therapy with Metoprolol tablets should be initiated 4-6 hours later. The initial oral dose should not exceed 50 mg t.i.d.
• Hyperthyroidism: Metoprolol 50 mg (one Metoprolol-50 tablet) four times a day. The dose should be reduced as the euthyroid state is achieved.
• Myocardial infarction: Orally, therapy should commence 15 minutes after the last injection with 50 mg every 6 hours for 48 hours. Patients who fail to tolerate the full intravenous dose should be given half the suggested oral dose. Maintenance- The usual maintenance dose is 200 mg daily given in divided doses. Elderly’ There are no special dosage requirements in otherwise healthy elderly patients. Significant hepatic dysfunction: A reduction in dosage may be necessary.

Extended-release tablet-

• Hypertension: The usual initial dosage is 25 to 100 mg daily in a single dose, whether used alone or added to a diuretic.
• Angina Pectoris: The dosage of extended-release Metoprolol Succinate should be individualized. The usual initial dosage is 100 mg daily, in a single dose.
• Heart Failure: The recommended starting dose of sustained-release Metoprolol Succinate is 25 mg once daily for two weeks in patients with NYHA class II heart failure and 12.5 mg once daily in patients with more severe heart failure. The dosage may be increased at weekly (or longer) intervals until optimum blood pressure reduction is achieved. If treatment is to be discontinued, the dosage should be reduced gradually over a period of 1-2 weeks.

IV Injection-

• Arrhythmias: By intravenous injection, up to 5 mg at a rate of 1-2 mg/minute, repeated after 5 minutes if necessary, total dose 10-15 mg.
• In surgery: By slow intravenous injection 2-4 mg at induction or to control arrhythmias developing during anaesthesia; 2 mg doses may be repeated to a maximum of 10 mg.
• Myocardial Infarction: Early intervention within 12 hours of infarction, by intravenous injection 5 mg every 2 minutes to a maximum of 15 mg, followed after 15 minutes by 50 mg by mouth every 6 hours for 48 hours; maintenance 200 mg daily in divided doses.

Tiredness, dizziness, depression, diarrhea, itching or rash, shortness of breath, slow heart rate, mental confusion, headache, somnolence, nightmares, insomnia, dyspnea, Nausea, dry mouth, gastric pain, constipation, flatulence, digestive tract disorders, heartburn, pruritus, musculoskeletal pain, blurred vision, decreased libido, and tinnitus have also been reported, intensification of AV block.

AV block, Uncontrolled heart failure, severe bradycardia, sick-sinus syndrome, cardiogenic shock and severe peripheral arterial disease. Known hypersensitivity to Metoprolol or other B-blockers. Metoprolol is also contra-indicated when myocardial infarction is complicated by significant bradycardia, first-degree heart block, systolic hypotension (<100mmHg) and/or severe heart failure.

Bronchospastic Diseases: Because of its relative beta 1 ‐selectivity, however, Metoprolol may be used with caution in patients with bronchospastic disease who do not respond to, or cannot tolerate other antihypertensive treatment.

Major Surgery: The necessity or desirability of withdrawing beta‐blocking therapy prior to major surgery is controversial; the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.

Diabetes and Hypoglycemia: Beta‐blockers may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be significantly affected. Peripheral Vascular Disease: Beta‐blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease. Calcium Channel Blockers: Because of significant inotropic and chronotropic effects in patients, caution should be exercised in patients treated with these agents concomitantly.

Catecholamine‐depleting drugs (e.g. Reserpine, Monoamine Oxidase (MAO) inhibitors) may have an additive effect when given with beta‐blocking agents. Drugs that inhibit CYP2D6 such as quinidine, fluoxetine, paroxetine and propafenone are likely to increase Metoprolol concentration. These increases in plasma concentration would decrease the cardioselectivity of Metoprolol. Concomitant use of digitalis glycosides and beta‐blockers can increase the risk of bradycardia. Beta‐blockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine.

Pregnancy Category C. There are no adequate and well‐controlled studies in pregnant women. This drug should be used during pregnancy only if clearly needed. Metoprolol is excreted in breast milk in very small quantities. Caution should be exercised when Metoprolol is administered to a nursing woman.

Hepatic impaired patient: Metoprolol should be used with caution in patients with impaired hepatic function.

Pediatric Use: No clinically relevant differences in the adverse event profile were observed for pediatric patients aged 6 to 16 years as compared with adult patients. Safety and effectiveness of Metoprolol have not been established in patients <6 years of age.

Geriatric Use: There were no notable differences in efficacy or the rate of adverse events between older and younger patients.

Poisoning due to an overdose of metoprolol may lead to severe hypotension, sinus bradycardia, atrioventricular block, heart failure, cardiogenic shock, cardiac arrest, bronchospasm, impairment of consciousness, coma, nausea, vomiting, cyanosis, hypoglycaemia and, occasionally, hyperkalaemia. The first manifestations usually appear 20 minutes to 2 hours after drug ingestion. Treatment: Treatment should include close monitoring of cardiovascular, respiratory and renal function, and blood glucose and electrolytes. Further absorption may be prevented by induction of vomiting, gastric lavage or administration of activated-charcoal if ingestion is recent. Cardiovascular complications should be treated symptomatically, which may require the use of sympathomimetic agents (e.g. noradrenaline, metaramionl), atropine or inotropic agents (e.g. dopamine, dobutamine). Temporary pacing may be required for AV block. Glucagon can reverse the effects of excessive B-blockade, given in a dose of 1-10 mg intravenously. Intravenous B2-stimulants e.g. terbutaline may be required to relieve bronchospasm. Metoprolol cannot be effectively removed by haemodialysis.

Store in a cool and dry place, protected from light.

Ophthalmic steroid - antibiotic combined preparations

Betamethasone is a corticosteroid which is effective in inflammatory dermatoses. It is also effective in less responsive conditions such as psoriasis.  Betamethasone has a 16β-methyl group that enhances the anti-inflammatory action of the molecule and reduces the sodium and water retaining properties of the fluorine atom bound at carbon 9.

Neomycin sulfate is bactericidal against many bacteria which are commonly associated with skin infections. Neomycin is a broad spectrum antibiotic which actively transported across the bacterial cell membrane, binds to a specific receptor protein on the 30s subunit of bacterial ribosomes, and interferes with an initiation complex between mRNA (messenger RNA) and the 30s subunit, inhibiting protein synthesis. DNA may be misread, thus producing nonfunctional proteins; polyribosomes are split apart and are unable to synthesize protein.

Drops:

• Eye: 1 drop instilled into the eye every one or two hours until control is achieved, when the frequency may be reduced.
• Ear: 2 or 3 drops instilled into the ear, every two or three hours until control is achieved, when the frequency can be reduced.
• Nose: 2 or 3 drops instilled into each nostril two or three times daily.

Eye Ointment: It should be applied thinly and evenly to the conjunctival sac at night (If eye drops used during day) or 3-4 times daily (if ointment used alone).

Acute sensitization to neomycin is a rare event but can occur after topical application to the eye. Eye drops containing corticosteroids cause a serious rise in intra-ocular pressure in a small percentage of the population, including most of those with a family history of glaucoma. A milder rise may be experienced by a larger proportion of subjects if treatment is continued for longer than a few weeks. Thinning of the cornea leading to perforation has occurred with use of topical corticosteroids. Cataract is reported to have occurred after unduly prolonged treatment of eye conditions with topical corticosteroids.

Viral, fungal, tuberculous or purulent conditions. Use in the eye is contra-indicated if glaucoma is present or where herpetic keratitis (e.g. dendritic ulcer) is considered a possibility. Inadvertent use of topical steroids in the latter condition can lead to extension of the ulcer and marked visual deterioration. Preparations containing neomycin should not be used for treating otitis externa when the ear drum is perforated, because of the risk of ototoxicity.

Steroids should not be administered to "red eyes" until a definitive diagnosis has been made. Ophthalmological treatment with steroid preparations should not be repeated or prolonged without regular review to exclude raised intra-ocular pressure or unsuspected infections. The unnecessary topical use of neomycin containing products should be avoided in order to minimize the occurrence of neomycin-resistant organisms (and organism cross-resistant to other aminoglycosides).

Pregnancy Category-Not Classified. FDA has not yet classified the drug into a specified pregnancy category. Topical administration of corticosteroid to pregnant animals can cause abnormalities of fetal development. The relevance of this finding to human beings has not been established; however, topical steroids should not be used extensively in pregnancy, i.e. in large amounts or for prolonged periods.

Store below 25° C

Ophthalmic steroid - antibiotic combined preparations

Betamethasone is a corticosteroid which is effective in inflammatory dermatoses. It is also effective in less responsive conditions such as psoriasis.  Betamethasone has a 16β-methyl group that enhances the anti-inflammatory action of the molecule and reduces the sodium and water retaining properties of the fluorine atom bound at carbon 9.

Neomycin sulfate is bactericidal against many bacteria which are commonly associated with skin infections. Neomycin is a broad spectrum antibiotic which actively transported across the bacterial cell membrane, binds to a specific receptor protein on the 30s subunit of bacterial ribosomes, and interferes with an initiation complex between mRNA (messenger RNA) and the 30s subunit, inhibiting protein synthesis. DNA may be misread, thus producing nonfunctional proteins; polyribosomes are split apart and are unable to synthesize protein.

Drops:

• Eye: 1 drop instilled into the eye every one or two hours until control is achieved, when the frequency may be reduced.
• Ear: 2 or 3 drops instilled into the ear, every two or three hours until control is achieved, when the frequency can be reduced.
• Nose: 2 or 3 drops instilled into each nostril two or three times daily.

Eye Ointment: It should be applied thinly and evenly to the conjunctival sac at night (If eye drops used during day) or 3-4 times daily (if ointment used alone).

Acute sensitization to neomycin is a rare event but can occur after topical application to the eye. Eye drops containing corticosteroids cause a serious rise in intra-ocular pressure in a small percentage of the population, including most of those with a family history of glaucoma. A milder rise may be experienced by a larger proportion of subjects if treatment is continued for longer than a few weeks. Thinning of the cornea leading to perforation has occurred with use of topical corticosteroids. Cataract is reported to have occurred after unduly prolonged treatment of eye conditions with topical corticosteroids.

Viral, fungal, tuberculous or purulent conditions. Use in the eye is contra-indicated if glaucoma is present or where herpetic keratitis (e.g. dendritic ulcer) is considered a possibility. Inadvertent use of topical steroids in the latter condition can lead to extension of the ulcer and marked visual deterioration. Preparations containing neomycin should not be used for treating otitis externa when the ear drum is perforated, because of the risk of ototoxicity.

Steroids should not be administered to "red eyes" until a definitive diagnosis has been made. Ophthalmological treatment with steroid preparations should not be repeated or prolonged without regular review to exclude raised intra-ocular pressure or unsuspected infections. The unnecessary topical use of neomycin containing products should be avoided in order to minimize the occurrence of neomycin-resistant organisms (and organism cross-resistant to other aminoglycosides).

Pregnancy Category-Not Classified. FDA has not yet classified the drug into a specified pregnancy category. Topical administration of corticosteroid to pregnant animals can cause abnormalities of fetal development. The relevance of this finding to human beings has not been established; however, topical steroids should not be used extensively in pregnancy, i.e. in large amounts or for prolonged periods.

Store below 25° C

Bisoprolol is indicated in-

• Hypertension
• Angina
• Moderate to severe heart failure

Bisoprolol is not recommended for the emergency treatment of hypertensive crises.

Anti adrenergic agent (Beta blockers), Beta-adrenoceptor blocking drugs, Beta-blockers

Bisoprolol Hemifumarate is the most selective ß1 blocker. It displays highest level of affinity for the ß1 receptor than any other beta-blocker available up to now. Selectively blocks ß1 adrenergic receptor in the heart and vascular smooth muscle and reduces heart rate and cardiac output resulting in decrease of arterial hypertension. Lipid metabolism can be adversely affected by ß-blockers, in patients with non-ß1 selective ß1-blocker, but Bisoprolol does not cause any change in the cholesterol fraction including the cardioprotective HDL-cholesterol, in long-term therapy.

Adult: In the treatment of mild to moderate hypertension, Bisoprolol fumarate must be individualized to the needs of the patient. The usual starting dose is 5 mg once daily either added to a diuretic or alone. If the response to 5 mg is inadequate, the dose may be increased to 10 mg and then, if necessary, to 20 mg once daily. An appropriate interval for dose titration is 2 weeks. Increasing the dose beyond 20 mg once daily produces only a small incremental benefit.

Children: Safety and effectiveness in children have not been established.

Patients With Renal or Hepatic Impairment: In patients with hepatic impairment (hepatitis or cirrhosis) or renal dysfunction (creatinine clearance less than 40 mL/min) as in other patients, the initial daily dose should be 5 mg. Because of the possibility of accumulation, caution must be used in dose titration. Since limited data suggest that bisoprolol fumarate is not dialysable, drug replacement is not necessary in patients undergoing dialysis.

Geriatrics: In the elderly, it is not usually necessary to adjust the dose, unless there is also significant renal or hepatic dysfunction

Bisoprolol, like any medication, may have some side effects. It is important that you keep your doctor informed of all side effects especially if you experience one of the following for several days. The most common side effects, whether or not caused by Bisoprolol, are: headache, fatigue, urinary tract infection, rhinitis or sinusitis (inflammation in the nose), diarrhea, dizziness, peripheral edema (swelling of the ankles), joint pain, cough, insomnia (trouble sleeping), nausea (feeling like vomiting), and sore throat. You must seek medical attention immediately if you experience an allergic reaction with symptoms of rash, itching, swelling, dizziness or trouble breathing.

Medicines affect different people in different ways. Just because side effects have occurred in other patients does not mean you will get them. Discuss how you feel on Bisoprolol with your doctor or pharmacist. Do not stop or restart Bisoprolol on your own.

In patients with cardiogenic shock, overt heart failure, second or third degree A-V block, right ventricular failure secondary to pulmonary hypertension and sinus bradycardia.

Monitoring of renal, hepatic and hematopoietic function should be performed at regular intervals during long-term treatment with bisoprolol.

Other β-blocking Agents: Bisoprolol fumarate should not be combined with other β-blocking agents.

Catecholamine-Depleting Drugs: Patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, should be monitored closely because the added β-adrenergic blocking action of bisoprolol fumarate may produce excessive reduction of sympathetic activity.

Centrally Active Antihypertensive Agents: β-blockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are coadministered, the β-blocker should be withdrawn several days before discontinuing clonidine. If replacing clonidine by β-blocker therapy, the introduction of β-blockers should be delayed for several days after clonidine administration has stopped (see also prescribing information for clonidine).

Antiarrhythmic Agents: Bisoprolol fumarate should be used with care when myocardial depressants or inhibitors of A-V conduction, such as certain calcium antagonists (particularly of the phenyl alkylamine (verapamil) and benzothiazepine (diltiazem) classes), or antiarrhythmic agents, such as disopyramide, are used concurrently.

Calcium Channel Blockers: Combined use of β-blockers and calcium channel blockers with negative inotropic effects can lead to prolongation of S-A and A-V conduction, particularly in patients with impaired ventricular function or conduction abnormalities. This may result in severe hypotension, bradycardia and cardiac failure.

Pregnancy: Bisoprolol fumarate was not teratogenic in rats at doses up to 150 mg/kg/day, which is 375 times the maximum recommended human daily dose. Bisoprolol fumarate was fetotoxic (increased late resorptions) at 50 mg/kg/day and maternotoxic (decreased food intake and body-weight gain) at 150 mg/kg/day. Bisoprolol fumarate was not teratogenic in rabbits at doses up to 12.5 mg/kg/day, which is 31 times the maximum recommended human daily dose, but was embryolethal (increased early resorptions) at 12.5 mg/kg/day. There are no studies in pregnant women. Bisoprolol fumarate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: Small amounts of bisoprolol fumarate (<2% of the dose) have been detected in the milk of lactating rats. It is not known whether this drug is excreted in human milk. If use of bisoprolol fumarate is considered essential, then mothers should stop nursing.

Keep in a dry place away from light and heat. Keep out of the reach of children.

Bisoprolol is indicated in-

• Hypertension
• Angina
• Moderate to severe heart failure

Bisoprolol is not recommended for the emergency treatment of hypertensive crises.

Anti adrenergic agent (Beta blockers), Beta-adrenoceptor blocking drugs, Beta-blockers

Bisoprolol Hemifumarate is the most selective ß1 blocker. It displays highest level of affinity for the ß1 receptor than any other beta-blocker available up to now. Selectively blocks ß1 adrenergic receptor in the heart and vascular smooth muscle and reduces heart rate and cardiac output resulting in decrease of arterial hypertension. Lipid metabolism can be adversely affected by ß-blockers, in patients with non-ß1 selective ß1-blocker, but Bisoprolol does not cause any change in the cholesterol fraction including the cardioprotective HDL-cholesterol, in long-term therapy.

Adult: In the treatment of mild to moderate hypertension, Bisoprolol fumarate must be individualized to the needs of the patient. The usual starting dose is 5 mg once daily either added to a diuretic or alone. If the response to 5 mg is inadequate, the dose may be increased to 10 mg and then, if necessary, to 20 mg once daily. An appropriate interval for dose titration is 2 weeks. Increasing the dose beyond 20 mg once daily produces only a small incremental benefit.

Children: Safety and effectiveness in children have not been established.

Patients With Renal or Hepatic Impairment: In patients with hepatic impairment (hepatitis or cirrhosis) or renal dysfunction (creatinine clearance less than 40 mL/min) as in other patients, the initial daily dose should be 5 mg. Because of the possibility of accumulation, caution must be used in dose titration. Since limited data suggest that bisoprolol fumarate is not dialysable, drug replacement is not necessary in patients undergoing dialysis.

Geriatrics: In the elderly, it is not usually necessary to adjust the dose, unless there is also significant renal or hepatic dysfunction

Bisoprolol, like any medication, may have some side effects. It is important that you keep your doctor informed of all side effects especially if you experience one of the following for several days. The most common side effects, whether or not caused by Bisoprolol, are: headache, fatigue, urinary tract infection, rhinitis or sinusitis (inflammation in the nose), diarrhea, dizziness, peripheral edema (swelling of the ankles), joint pain, cough, insomnia (trouble sleeping), nausea (feeling like vomiting), and sore throat. You must seek medical attention immediately if you experience an allergic reaction with symptoms of rash, itching, swelling, dizziness or trouble breathing.

Medicines affect different people in different ways. Just because side effects have occurred in other patients does not mean you will get them. Discuss how you feel on Bisoprolol with your doctor or pharmacist. Do not stop or restart Bisoprolol on your own.

In patients with cardiogenic shock, overt heart failure, second or third degree A-V block, right ventricular failure secondary to pulmonary hypertension and sinus bradycardia.

Monitoring of renal, hepatic and hematopoietic function should be performed at regular intervals during long-term treatment with bisoprolol.

Other β-blocking Agents: Bisoprolol fumarate should not be combined with other β-blocking agents.

Catecholamine-Depleting Drugs: Patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, should be monitored closely because the added β-adrenergic blocking action of bisoprolol fumarate may produce excessive reduction of sympathetic activity.

Centrally Active Antihypertensive Agents: β-blockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are coadministered, the β-blocker should be withdrawn several days before discontinuing clonidine. If replacing clonidine by β-blocker therapy, the introduction of β-blockers should be delayed for several days after clonidine administration has stopped (see also prescribing information for clonidine).

Antiarrhythmic Agents: Bisoprolol fumarate should be used with care when myocardial depressants or inhibitors of A-V conduction, such as certain calcium antagonists (particularly of the phenyl alkylamine (verapamil) and benzothiazepine (diltiazem) classes), or antiarrhythmic agents, such as disopyramide, are used concurrently.

Calcium Channel Blockers: Combined use of β-blockers and calcium channel blockers with negative inotropic effects can lead to prolongation of S-A and A-V conduction, particularly in patients with impaired ventricular function or conduction abnormalities. This may result in severe hypotension, bradycardia and cardiac failure.

Pregnancy: Bisoprolol fumarate was not teratogenic in rats at doses up to 150 mg/kg/day, which is 375 times the maximum recommended human daily dose. Bisoprolol fumarate was fetotoxic (increased late resorptions) at 50 mg/kg/day and maternotoxic (decreased food intake and body-weight gain) at 150 mg/kg/day. Bisoprolol fumarate was not teratogenic in rabbits at doses up to 12.5 mg/kg/day, which is 31 times the maximum recommended human daily dose, but was embryolethal (increased early resorptions) at 12.5 mg/kg/day. There are no studies in pregnant women. Bisoprolol fumarate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: Small amounts of bisoprolol fumarate (<2% of the dose) have been detected in the milk of lactating rats. It is not known whether this drug is excreted in human milk. If use of bisoprolol fumarate is considered essential, then mothers should stop nursing.

Keep in a dry place away from light and heat. Keep out of the reach of children.

Bisoprolol & Amlodipine combination is indicated for the treatment of hypertension as substitution therapy in patients adequately controlled with the individual products given concurrently at the same dose level as in the combination, but as separate tablets

Anti-hypertensive

This consists of Amlodipine and Bisoprolol Fumarate. Amlodipine is a dihydropyridine calcium antagonist that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Amlodipine acts directly on vessels to cause a reduction in peripheral vascular resistance and reduction in blood pressure.

Bisoprolol Fumarate is a synthetic, beta1-selective (cardioselective) adrenoceptor blocking agent, lacking intrinsic sympathomimetic and relevant membrane stabilizing activity. It only shows low affinity to the beta2 receptor of the smooth muscles of bronchi and vessels as well as to the beta2-receptors concerned with metabolic regulation. Therefore, bisoprolol is generally not to be expected to influence airway resistance and beta2-mediated metabolic effects. Its beta1-selectivity extends beyond the therapeutic dose range.

One tablet once daily in patients whose blood pressure is adequately controlled with separately administered monocomponent products of the same doses as the recommended fixed-dose combination.

Common: Dizziness, headache, somnolence, palpitations, flushing, feeling of coldness or numbness in the extremities, gastrointestinal complaints such as nausea, vomiting, diarrhea, constipation, abdominal pain; edema (e.g. ankle edema), fatigue.

Uncommon: Insomnia, mood changes (incl. anxiety), depression, sleep disorders, hypaesthesia, paresthesia, dysgeusia, tremor, visual disturbances (incl. diplopia), tinnitus, AV conduction disturbances, worsening of pre existing heart failure, bradycardia, hypotension, syncope, dyspnea, bronchospasm in patients with bronchial asthma or a history of obstructive airway disease, rhinitis, dyspepsia, dry mouth, alopecia, purpura, skin discoloration, pruritus, exanthema, arthralgia, myalgia, muscular weakness, muscle cramps, back pain, micturition disorder, nocturia, pollakisuria, potency disorders, gynecomastia, asthenia, chest pain, pain, malaise, weight increase, weight decrease.

Rare: Allergic reactions mainly affecting the skin, nightmares, hallucinations, confusion, decreased tear secretion, hearing disorders, allergic rhinitis, hepatitis, increased triglycerides, increased liver enzymes (ALAT, ASAT).

Acute heart failure or during episodes of heart failure decompensation, obstruction of the outflow tract of the left ventricle (e.g. high grade aortic stenosis), cardiogenic shock, second or third degree AV block, sick sinus syndrome, sinoatrial block, symptomatic bradycardia or hypotension, severe bronchial asthma, severe forms of peripheral arterial occlusive disease or severe forms of Raynaud’s syndrome, untreated phaeochromocytoma metabolic acidosis, hypersensitivity to bisoprolol, amlodipine, dihydropyridine derivates or to any of the excipients.

Patients with heart failure should be treated with caution. An increased risk of a further deterioration of the ventricular pump function cannot be excluded. Since the abrupt withdrawal of bisoprolol may lead to a transitory worsening of the clinical condition, especially in patients with ischemic heart disease, the treatment must not be stopped abruptly. Caution is advised in patients with impaired hepatic function. Beta-blockers should be avoided in patients with obstructive airways diseases unless there are compelling clinical reasons for their use. Due to the bisoprolol component treatment must be used with caution in: bronchospasm (bronchial asthma, chronic obstructive airways disease; concomitant bronchodilating therapy may be recommended); diabetes mellitus showing large fluctuations in blood glucose values, symptoms of hypoglycemia can be masked; strict fasting; ongoing desensitization therapy; first degree AV block; Prinzmetal’s angina; peripheral arterial occlusive disease. Patients with psoriasis or with a history of psoriasis should only be given beta-blockers (e.g. bisoprolol) after a careful balancing of benefits and risks. Symptoms of thyrotoxicosis may be masked. In patients undergoing general anesthesia, the anesthetist must be aware of beta-blockade. If it is thought necessary to withdraw beta blocker therapy before surgery, this should be done gradually and completed about 48 hours before anesthesia.

Combinations not recommended: Calcium antagonists of the verapamil and diltiazem type, centrally-acting antihypertensive drugs.

Combinations to be used with caution: Strong or moderate CYP3A4 inhibitors, CYP3A4 inducers, simvastatin, Tacrolimus, Cyclosporine, class I antiarrhythmic drugs, class III antiarrhythmic drugs, parasympathomimetic drugs, topical beta-blockers (e.g. eye drops), insulin and oral antidiabetic drugs, anesthetic agents, digitalis glycosides, non-steroidal anti-inflammatory drugs (NSAIDs), sympathomimetic agents, antihypertensive agents and other drugs with blood pressure lowering potential.

Combinations to be considered: Mefloquine, Rifampicin, Ergotamine derivatives, MAO inhibitors (except MAO-B inhibitor).

Pregnancy and Lactation: Not recommended.

Geriatric use: The usual doses can be administered to elderly people; however, caution is advised when the dose is increased.

Pediatric use: The safety and efficacy of Bisoprolol fumarate/amlodipine in children and adolescents below the age of 18 years have not been established. No data are available.

Patients with Liver disease: In case of hepatic impairment elimination of amlodipine may be elongated. Exact dosage recommendations concerning amlodipine have not been established, but the drug should therefore be administered with special caution in these patients. In case of severe hepatic impairment, the daily dose of bisoprolol must not exceed 10 mg.

Patients with Kidney disease: No dosage adjustment is required for patients with mild to moderate renal impairment. Amlodipine is not dialyzable. Amlodipine should be administered with particular caution to patients undergoing dialysis. In case of severe renal impairment (creatinine clearance <20 ml/min) the daily dose of bisoprolol must not exceed 10 mg

Most common signs expected with overdose of a beta-blocker are bradycardia, hypotension, bronchospasm, acute cardiac insufficiency, hypoglycemia. According to available data gross overdose of amlodipine could result in excessive peripheral vasodilation and possibly reflex tachycardia. Marked and probably prolonged systemic hypotension up to and including shock with fatal outcome have been reported. In general, if overdose occurs, discontinuation of treatment and supportive and symptomatic treatment is recommended.

Keep in a dry place, below 30°C. Protect from light. Keep out of the reach of children.

Bisoprolol plus Hydrochlorothiazide is indicated in the treatment of Hypertension.

Combined antihypertensive preparations

Bisoprolol Fumarate and Hydrochlorothiazide have been used individually and in combination for the treatment of hypertension. The antihypertensive effects of these agents are additive; Hydrochlorothiazide 6.25 mg significantly increases the antihypertensive effect of Bisoprolol Fumarate. The incidence of hypokalemia with the Bisoprolol Fumarate and Hydrochlorothiazide 6.25 mg combination is significantly lower than with Hydrochlorothiazide 25 mg. Bisoprolol Fumarate is a β1-selective (cardioselective) adrenoceptor blocking agent without significant membrane stabilizing or intrinsic sympathomimetic activities in its therapeutic dose range. Hydrochlorothiazide is a benzothiadiazine diuretic. Thiazides affect renal tubular mechanisms of electrolyte reabsorption and increase excretion of sodium and chloride in approximately equivalent 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 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.

Generally well tolerated. Most side effects have been mild and transient. Side effects which may occur: fatigue, dizziness, headache, bradycardia, arrhythmia, peripheral ischemia, chest pain, palpitations, rhythm disturbances, cold extremities, claudication, orthostatic hypotension, diarrhoea, constipation, nausea, dyspepsia, rhinitis, pharyngitis etc.

It is contraindicated in patients in cardiogenic shock, overt cardiac failure, second or third degree AV block, marked sinus bradycardia, anuria and hypersensitivity to either component of this product or to other sulfonamide-derived drugs.

Hyperuricemia or acute gout may be precipitated in certain patients receiving thiazide diuretics. Warning signs or symptoms of fluid and electrolyte imbalance include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia and gastrointestinal disturbances such as nausea and vomiting. Hypokalemia may develop. If withdrawal of this combination therapy is planned, it should be achieved gradually over a period of about 2 weeks. Patients should be carefully observed.

This combination drug may potentiate the action of other antihypertensive agents used concomitantly. This combination drug should not be combined with other beta-blocking agents. Patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, should be closely monitored because the added beta-adrenergic blocking action of Bisoprolol Fumarate may produce excessive reduction of sympathetic activity. In patients receiving concurrent therapy with clonidine, if therapy is to be discontinued, it is suggested that this combination drug be discontinued for several days before the withdrawal of clonidine. This combination drug should be used with caution when myocardial depressants or inhibitors of AV conduction, such as certain calcium antagonists (particularly of the phenylalkylamine [verapamil] and benzothiazepine [diltiazem] classes) or antiarrhythmic agents, such as disopyramide, are used concurrently. Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Use in Pregnancy: Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Bisoprolol Fumarate and Hydrochlorothiazide should be used during pregnancy only if the potential benefit justifies the risk to the fetus.

Use in Nursing Mothers: Bisoprolol Fumarate alone or in combination with Hydrochlorothiazide has not been studied in nursing mothers. Thiazides are excreted in human breast milk. Small amounts of Bisoprolol Fumarate have been detected in the milk of lactating rats. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

There are limited data on overdose with this combination product. The most frequently observed signs expected with overdosage of a beta-blocker are bradycardia and hypotension. Lethargy is also common and with severe overdoses, delirium, coma, convulsions, and respiratory arrest have been reported to occur. Congestive heart failure, bronchospasm, and hypoglycemia may occur. With thiazide diuretics, acute intoxication is rare. The most prominent feature of overdose is acute loss of fluid and electrolytes. Signs and symptoms include cardiovascular (tachycardia, hypotension, shock), neuromuscular (weakness, confusion, dizziness, cramps of the calf muscles, paresthesia, fatigue, impairment of consciousness), gastrointestinal (nausea, vomiting, thirst), renal (polyuria, oliguria, or anuria), and laboratory findings (hypokalemia, hyponatremia, hypochloremia, alkalosis, increased BUN [especially in patients with renal insufficiency]).

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

Bisoprolol plus Hydrochlorothiazide is indicated in the treatment of Hypertension.

Combined antihypertensive preparations

Bisoprolol Fumarate and Hydrochlorothiazide have been used individually and in combination for the treatment of hypertension. The antihypertensive effects of these agents are additive; Hydrochlorothiazide 6.25 mg significantly increases the antihypertensive effect of Bisoprolol Fumarate. The incidence of hypokalemia with the Bisoprolol Fumarate and Hydrochlorothiazide 6.25 mg combination is significantly lower than with Hydrochlorothiazide 25 mg. Bisoprolol Fumarate is a β1-selective (cardioselective) adrenoceptor blocking agent without significant membrane stabilizing or intrinsic sympathomimetic activities in its therapeutic dose range. Hydrochlorothiazide is a benzothiadiazine diuretic. Thiazides affect renal tubular mechanisms of electrolyte reabsorption and increase excretion of sodium and chloride in approximately equivalent 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 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.

Generally well tolerated. Most side effects have been mild and transient. Side effects which may occur: fatigue, dizziness, headache, bradycardia, arrhythmia, peripheral ischemia, chest pain, palpitations, rhythm disturbances, cold extremities, claudication, orthostatic hypotension, diarrhoea, constipation, nausea, dyspepsia, rhinitis, pharyngitis etc.

It is contraindicated in patients in cardiogenic shock, overt cardiac failure, second or third degree AV block, marked sinus bradycardia, anuria and hypersensitivity to either component of this product or to other sulfonamide-derived drugs.

Hyperuricemia or acute gout may be precipitated in certain patients receiving thiazide diuretics. Warning signs or symptoms of fluid and electrolyte imbalance include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia and gastrointestinal disturbances such as nausea and vomiting. Hypokalemia may develop. If withdrawal of this combination therapy is planned, it should be achieved gradually over a period of about 2 weeks. Patients should be carefully observed.

This combination drug may potentiate the action of other antihypertensive agents used concomitantly. This combination drug should not be combined with other beta-blocking agents. Patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, should be closely monitored because the added beta-adrenergic blocking action of Bisoprolol Fumarate may produce excessive reduction of sympathetic activity. In patients receiving concurrent therapy with clonidine, if therapy is to be discontinued, it is suggested that this combination drug be discontinued for several days before the withdrawal of clonidine. This combination drug should be used with caution when myocardial depressants or inhibitors of AV conduction, such as certain calcium antagonists (particularly of the phenylalkylamine [verapamil] and benzothiazepine [diltiazem] classes) or antiarrhythmic agents, such as disopyramide, are used concurrently. Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Use in Pregnancy: Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Bisoprolol Fumarate and Hydrochlorothiazide should be used during pregnancy only if the potential benefit justifies the risk to the fetus.

Use in Nursing Mothers: Bisoprolol Fumarate alone or in combination with Hydrochlorothiazide has not been studied in nursing mothers. Thiazides are excreted in human breast milk. Small amounts of Bisoprolol Fumarate have been detected in the milk of lactating rats. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

There are limited data on overdose with this combination product. The most frequently observed signs expected with overdosage of a beta-blocker are bradycardia and hypotension. Lethargy is also common and with severe overdoses, delirium, coma, convulsions, and respiratory arrest have been reported to occur. Congestive heart failure, bronchospasm, and hypoglycemia may occur. With thiazide diuretics, acute intoxication is rare. The most prominent feature of overdose is acute loss of fluid and electrolytes. Signs and symptoms include cardiovascular (tachycardia, hypotension, shock), neuromuscular (weakness, confusion, dizziness, cramps of the calf muscles, paresthesia, fatigue, impairment of consciousness), gastrointestinal (nausea, vomiting, thirst), renal (polyuria, oliguria, or anuria), and laboratory findings (hypokalemia, hyponatremia, hypochloremia, alkalosis, increased BUN [especially in patients with renal insufficiency]).

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

Corticosteroid

Betamethasone Valerate BP is a synthetic adrenocorticosteroid, which is glucocorticoid in nature. It is an analog of prednisolone that also possesses a slight degree of mineral corticosteroid activity. Due to its anti-inflammatory, antipruritic and vasoconstrictive activity, it is very effective and suitable for dermatological use. It is absorbed from the skin and inflammation and/or another disease process in the skin increase percutaneous absorption from the skin. Occlusive dressings substantially increase its percutaneous absorption.

Apply sparingly to the affected area two or three times daily until improvement occurs, then twice daily or less. The usual maximum duration of therapy is three weeks.

The following local adverse reactions are more common with the use of high doses, long term use and with the use of occlusive dressings of Cream/Ointment: dryness, itching, burning, skin thinning, local irritation, features of hypercorticolism, telagiectasia, striaea, skin atrophy. hypertrichosis, change in pigmentation, secondary infection, perioral dermatiis, allergic contact dermatitis, maceration of the skin, acneform eruption, exacerbation of symptoms.

Betamethasone Valerate cream or ointment is contraindicated in the following conditions :

• Hypersensitivity to any of the ingredients in the preparation.
• Rosaceae & acne vulgaris.
• Perioral dermatitis, perianal & genital pruritis.
• Viral infections of the skin, e.g. herpes simplex & chicken pox.
• Primary infected skin lesions caused by fungi or bacteria.
• Dermatoses in children under one year of age.

Betamethasone Cream/Ointment is usually well tolerated but if signs of hypersensitivity appear, application should be stopped. Long term continuous topical therapy should be avoided where possible, particularly in children as adrenal suppression may occur even without occlusion. When extensive areas are treated, sufficient systemic absorption may occur to produce symptoms of hypercorticolism. This effect is more likely if occlusive dressings are used, or if the treatment is prolonged. The face or other areas of the body may exhibit atrophic changes after prolonged treatment. If applied to the eyelids, care is needed to ensure that the preparation does not enter the eye, as glaucoma might result. Any spread of the infection requires withdrawal of topical corticosteroid therapy.

There are no significant drug interactions reported with Betamethasone Cream/Ointment.

It should not be used extensively in pregnancy.

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

This cream is usually useful for the treatment of superficial infections caused by gram-positive and gramnegative microorganisms. It is also useful in burns, regeneration of new skin in wounds and ulceration, otitis externa, postoperative infections, neuro-dermatitis and eczema. It may be used as an adjunct to systemic steroid therapy in special kind of pyoderma.

Aural steroid & antibiotic combined preparations

Betamethasone is an active topical corticosteroid, which produces a rapid response in the inflammatory dermatoses and cures psoriasis types of skin diseases. Neomycin Sulfate is a topical broad-spectrum bactericidal amino-glycoside effective against various kinds of gram-positive and gramnegative pathogens such as Proteus vulgaris, Staphylococcus aureus etc. This preparation has effective penetration and uniform distribution capacity, so it is very effective in hairy and intertriginous places. This preparation is very effective for the treatment of wet ulceration of the skin.

Use in adults: This preparation should be applied to the affected parts of the skin as a thin layer for 3 to 4 times daily. In chronic conditions, withdrawal of treatment is carried out by decreasing the frequency of application until the cream is applied as infrequently as once a week. Or as directed by the physician.

Use in children: Do not use it on children under 1 year of age. A course of treatment for a child should not normally last more than 5 days unless otherwise stated by your physician.

This preparation is well tolerated. But prolonged and high doses may cause Cushing's syndrome, acne, thinning and dilatation of blood vessels, particularly when occlusive dressings are used.

This preparation is contraindicated to the patients who are hypersensitive to any of its components. It should not be used for the treatment of otitis externa when the eardrum is perforated. It is contraindicated in skin lesions caused by infection with viruses and fungi.

Long term continuous topical therapy of this preparation should be avoided, which may produce many resistant micro organisms. So, accurate dose of this preparation should be used in infected areas only.

There are no significant drug interactions reported with Betamethasone Valerate BP and Neomycin Sulphate BP Cream/Ointment.

This preparation should not be used extensively in pregnancy.

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.