Bisoren Plus 5 Tablet

Bisoren Plus 5 Tablet is used for: Hypertension, Congestive heart failure, HTN, Angina pectoris

Adult: Oral Initial: 2.5 mg/6.25 mg tablet once daily. Increase based on clinical response in 2 weeks. Maximum: bisoprolol 20 mg/hydrochlorothiazide 12.5 mg once daily.

Renal Impairment Use caution in dosing/titrating patients with renal dysfunction Cumulative effects of thiazides may develop with impaired renal function CrCl <40mL/min: half-life of bisoprolol fumarate is increased up to threefold

May be taken with or without food. Withdraw gradually over about 2 weeks

Anuria Cardiogenic shock Heart block 2°/3° Hypersensitivity to either component or sulfonamide derivatives Overt cardiac failure Marked sinus bradycardia

Although the probability of developing hypokalemia is reduced with therapy because of very low dose of HCTZ employed, periodic determination of serum electrolytes should be performed, and patients should be observed for signs of fluid or electrolyte disturbances, eg, hyponatremia, hypochloremic alkalosis, hypokalemia, and hypomagnesemia Thiazides have been shown to increase urinary excretion of magnesium; this may result in hypomagnesemia; 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, especially with brisk diuresis when severe cirrhosis is present, during concomitant use of corticosteroids or adrenocorticotropic hormone (ACTH) or after prolonged therapy; interference with adequate oral electrolyte intake will also contribute to hypokalemia; hypokalemia and hypomagnesemia can provoke ventricular arrhythmias or sensitize or exaggerate the response of the heart to the toxic effects of digitalis; hypokalemia may be avoided or treated by potassium supplementation or increased intake of potassium-rich foods Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction rather than salt administration, except in rare instances when hyponatremia is life-threatening; in actual salt depletion, appropriate replacement is therapy of choice Calcium excretion is decreased by thiazides, and pathologic changes in parathyroid glands, with hypercalcemia and hypophosphatemia, have been observed in a few patients on prolonged thiazide therapy Hyperuricemia or acute gout may be precipitated in certain patients receiving thiazide diuretics; bisoprolol fumarate, alone or in combination with HCTZ, has been associated with increases in uric acid; however, in U.S. clinical trials, the incidence of treatment-related increases in uric acid was higher during therapy with HCTZ 25 mg (25%) than with B/H 6.25 mg (10%); because of the very low dose of HCTZ employed, hyperuricemia may be less likely with this drug combination In general, beta-blocking agents should be avoided in patients with overt congestive failure; however, in some patients with compensated cardiac failure, it may be necessary to utilize these agents; in such situations, they must be used cautiously Continued depression of the myocardium with beta-blockers can, in some patients, precipitate cardiac failure; at the first signs or symptoms of heart failure, discontinuation of therapy should be considered; in some cases, therapy can be continued while heart failure is treated with other drugs Exacerbations of angina pectoris and, in some instances, myocardial infarction or ventricular arrhythmia, are observed in patients with coronary artery disease following abrupt cessation of therapy with beta-blockers; such patients should be cautioned against interruption or discontinuation of therapy without physician’s advice; even in patients without overt coronary artery disease, it may be advisable to taper therapy with over approximately 1 week with patient under careful observation; if withdrawal symptoms occur, beta-blocking agent therapy should be reinstituted,at least temporarily Beta-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease; exercise caution in such individuals Patients with bronchospastic pulmonary disease should, in general, not receive beta-blockers; because of relative beta1 selectivity of bisoprolol fumarate, the drug may be used with caution in patients with bronchospastic disease who do not respond to, or who cannot tolerate other antihypertensive treatment; Since beta1- selectivity is not absolute, the lowest possible dose of ZIAC should be used. Abeta2 agonist (bronchodilator) should be made available Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery; however, impaired ability of the heart to respond to reflex adrenergic stimuli may augment risks of general anesthesia and surgical procedures Beta-blockers may prevent early warning signs of hypoglycemia, such as tachycardia, and increase the risk for severe or prolonged hypoglycemia at any time during treatment, especially in patients with diabetes mellitus or children and patients who are fasting (eg, surgery, not eating regularly, or are vomiting); if severe hypoglycemia occurs, patients should be instructed to seek emergency treatment Nonselective beta-blockers may potentiate insulin-induced hypoglycemia and delay recovery of serum glucose levels; because of its beta1-selectivity, this is less likely with bisoprolol fumarate; however, patients subject to spontaneous hypoglycemia, or diabetic patients receiving insulin or oral hypoglycemic agents, should be cautioned about these possibilities; also, latent diabetes mellitus may become manifest and diabetic patients given thiazides may require adjustment of insulin dose; because of the very low dose of HCTZ employed, this may be less likely with this drug combination Beta-adrenergic blockade may mask clinical signs of hyperthyroidism, such as tachycardia; abrupt withdrawal of beta-blockade may be followed by exacerbation of symptoms of hyperthyroidism or may precipitate thyroid storm Cumulative effects of thiazides may develop in patients with impaired renal function; in such patients, thiazides may precipitate azotemia; in subjects with creatinine clearance < 40 mL/min, the plasma half-life of bisoprolol fumarate is increased up to threefold, as compared to healthy subjects; if progressive renal impairment becomes apparent, therapy should be discontinued This drug combination should be used with caution in patients with impaired hepatic function or progressive liver disease; thiazides may alter fluid and electrolyte balance, which may precipitate hepatic coma; also, elimination of bisoprolol fumarate is significantly slower in patients with cirrhosis than in healthy subjects Angle-closure glaucoma Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute angle-closure glaucoma and elevated intraocular pressure with or without a noticeable acute myopic shift and/or choroidal effusions Symptoms may include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation Untreated, the acute angle-closure glaucoma may result in permanent visual field loss The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible; prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy Instruct patients taking hydrochlorothiazide to immediately consult their healthcare provider if visual field defects, decreased visual acuity, or ocular pain occur

Pregnancy There are no adequate and well-controlled studies on pregnant women; therapy should be used during pregnancy only if potential benefit justifies risk to fetus Animal data In rats, bisoprolol fumarate/hydrochlorothiazide (B/H) combination was not teratogenic at doses up to 51.4 mg/kg/day of bisoprolol fumarate in combination with 128.6 mg/kg/day of hydrochlorothiazide; bisoprolol fumarate and hydrochlorothiazide doses used in rat study are, as multiples of MRHD in combination, 129 and 514 times greater, respectively, on a bodyweight basis, and 26 and 106 times greater, respectively, on basis of body surface area The drug combination was maternotoxic (decreased body weight and food consumption) at B5.7/H14.3 (mg/kg/day) and higher, and fetotoxic (increased late resorptions) at B17.1/H42.9 (mg/kg/day) and higher; maternotoxicity was present at 14/57 times MRHD of B/H, respectively, on a bodyweight basis, and 3/12 times MRHD of B/H doses, respectively, on basis of body surface area Fetotoxicity was present at 43/172 times the MRHD of B/H, respectively, on body weight basis, and 9/35 times MRHD of B/H doses, respectively, on basis of body surface area; in rabbits, the B/H combination was not teratogenic at doses of B10/H25 (mg/kg/day); bisoprolol fumarate and hydrochlorothiazide used in rabbit study were not teratogenic at 25/100 times B/H MRHD, respectively, on a bodyweight basis, and 10/40 times B/H MRHD, respectively, on basis of body surface area The drug combination was maternotoxic (decreased body weight) at B1/H2.5 (mg/kg/day) and higher, and fetotoxic (increased resorptions) at B10/H25 (mg/kg/day); the multiples of the MRHD for the B/H combination that were maternotoxic are, respectively, 2.5/10 (on the basis of body weight) and 1/4 (on the basis of body surface area), and for fetotoxicity were, respectively 25/100 (on basis of body weight) and 10/40 (on basis of body surface area) Thiazides cross the placental barrier and appear in the cord blood; the use of thiazides in pregnant women requires that anticipated benefit be weighed against possible hazards to the fetus; these hazards include fetal or neonatal jaundice, pancreatitis, thrombocytopenia, and possibly other adverse reactions that have occurred in the adult See also individual agents Impairment of fertility Reproduction studies in rats did not show impairment of fertility with bisoprolol fumarate/hydrochlorothiazide combination doses containing up to 30 mg/kg/day of bisoprolol fumarate in combination with 75 mg/kg/day of hydrochlorothiazide On a bodyweight basis, these doses are 75 and 300 times, respectively, MRHD of bisoprolol fumarate and hydrochlorothiazide; on body surface area basis, these study doses are 15 and 62 times, respectively, MRHD Lactation Bisoprolol fumarate alone or in combination with HCTZ has not been studied in nursing mothers; thiazides are excreted in human breast milk; small amounts of bisoprolol fumarate(<2% of the dose) have been detected in milk of lactating rats; because of potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue drug, taking into account importance of drug to mother

Bisoprolol : May potentiate AV conduction time and may increase negative inotropic effect w/ class I antiarrhythmic drugs (e.g. quinidine, disopyramide, propafenone). Concomitant catecholamine-depleting drugs (e.g. reserpine, guanethidine) may produce excessive sympathetic activity. May exacerbate rebound HTN upon discontinuance of clonidine treatment. Increased risk of bradycardia w/ digitalis glycosides. Reduced hypotensive effect w/ NSAIDs. Hydrochlorothiazide: Increases toxicity of lithium. May potentiate orthostatic hypotension w/ barbiturates and narcotics. Enhanced neuromuscular blocking action of competitive neuromuscular blockers (e.g. atracurium). Increased hypokalaemic effect w/ corticosteroids, corticotropin, ?2 agonists (e.g. salbutamol). Additive effect w/ other antihypertensives. Potentiation of orthostatic hypotension w/ barbiturates or opioids. Reduced antihypertensive effect by drugs that cause fluid retention (e.g. corticosteroids, NSAIDs, carbenoxolone). Enhanced nephrotoxicity of NSAIDs. Reduced therapeutic effect of antidiabetics. Contraindicated (0) Serious (34) acebutolol aminolevulinic acid oral aminolevulinic acid topical atenolol betaxolol carbamazepine carvedilol celiprolol clonidine cyclophosphamide cyclosporine digoxin diltiazem dofetilide esmolol fexinidazole isocarboxazid labetalol lofexidine mavacamten methyl aminolevulinate metoprolol nadolol nebivolol penbutolol pindolol propranolol rivastigmine sotalol squill timolol tretinoin tretinoin topical verapamil

Side effects of Bisoprolol + Hydrochlorothiazide : 1-10% Bisoprolol fumarate Arthralgia (3%), asthenia (2%), cough (3%), diarrhea (4%), dizziness (10%), dry mouth (1%), dyspnea (2%), fatigue (8%), headache (11%), hypoaesthesia (2%), insomnia (3%), nausea (2%), peripheral edema (4%), pharyngitis (2%), rhinitis (4%), sinusitis (2%), upper respiratory infection (5%), vomiting (2% ) Hydrochlorothiazide Anorexia,Epigastric distress,Hypokalemia,Hypotension,Orthostatic hypotension,Phototoxicity Frequency Not Defined Bisoprolol fumarate Aggravate CHF, cold extremeties, decrease HDL, depression, hypotension, increase bronchospasm, increase triglycerides, mask symptoms of hypoglycemia, muscle & joint pain Hydrochlorothiazide Agranulocytosis, anaphylaxis, anemia, Confusion, erythema multiforme skin reactions including Stevens-Johnson syndrome Exfoliative dermatitis including toxic epidermal necrolysis, Hypomagnesemia, hyponatremia, hypochloremia, dizziness, fatigue, headache, hypercalcemia, hyperuricemia, hyperglycemia, hyperlipidemia, hypercholesterolemia, muscle weakness or cramps, nausea, purpura, rash, vertigo, vomiting Potentially Fatal: AV block, bradycardia. Rare but may occur in patients with preexisting cardiac disease. Includes severe bronchospasm, hypoglycaemia, hypotension, orthostatic hypotension, bradyarrhythmias. 'Rebound phenomenon' leading to unstable angina or MI on sudden withdrawal.

Bisoprolol fumarate/hydrochlorothiazide is a fixed-combination tablet that combines a Beta adrenergic receptor blocker, bisoprolol fumarate, and a thiazide diuretic, hydrochlorothiazide. Bisoprolol fumarate, a cardioselective inhibitor of beta(1)-adrenoceptor, has no significant intrinsic sympathomimetic activity or membrane stabilizing activity in its therapeutic dosage; exhibits beta(2)-adrenoceptors inhibition and negative chronotropic effect. Hydrochlorothiazide is a thiazide diuretic that inhibits Na reabsorption in distal renal tubules resulting in increased excretion of Na+ and water, also K+ and H+ ions.

Bisoren Plus 5 5mg + 6.25mg Tablet manufactured by Renata PLC.. Its generic name is Bisoprolol + Hydrochlorothiazide. Bisoren Plus 5 is availble in Bangladesh. Farmaco BD drug index information on Bisoren Plus 5 Tablet is not intended for diagnosis, medical advice or treatment; neither intended to be a substitute for the exercise of professional judgment.