Full Prescribing Info
Contents
Bisoprolol hemifumarate, hydrochlorothiazide.
Description
Each tablet contains bisoprolol hemifumarate 2.5 or 5 mg and hydrochlorothiazide 6.25 mg.
Action
Pharmacotherapeutic Group: Selective β1-adrenoreceptor blocker and diuretic.
Pharmacology: Mode of Action: Clinical studies have demonstrated synergy for the β-blocker/diuretic combination and its efficacy at ¼ of the standard doses (5 mg/6.25 mg) in the treatment of mild to moderate hypertension.
The pharmacodynamic effects eg, hypokalemia (hydrochlorothiazide) and bradycardia, asthenia and headache (bisoprolol) are dose-dependent. The combination of the 2 active substances at ¼ of the usual doses (5 mg/6.25 mg) aims to reduce these effects.
Bisoprolol is a highly selective β1-adrenoreceptor inhibitor, devoid of intrinsic sympathomimetic activity or significant membrane-stabilizing effects. As for other β1-receptor antagonists, the mode of action of bisoprolol in hypertension is not well understood, but it has been shown that the substance distinctly lowers serum renin and slows down the heart rate.
Hydrochlorothiazide is a thiazide diuretic with antihypertensive activity. Its diuretic effect is due to inhibition of the active transport of Na+ from renal tubules into blood, preventing reabsorption of Na+.
Indications/Uses
Treatment of hypertension.
Dosage/Direction for Use
Adults and the Elderly: Usual Starting Dose: 1 tab Lodoz 2.5 once daily. If the antihypertensive effect of this dosage is inadequate, the dose will be increased to 1 tab Lodoz 5 once daily and if response is still inadequate, to maximum dose 1 tab Lodoz 10 once daily. Dose adjustment is not necessary in cases of mild or moderate liver or renal failure (creatinine clearance >30 mL/min).
Children: There is no paediatric experience with bisoprolol, and it is not therefore recommended for children.
Overdosage
In the event of overdose or of a sudden reduction in heart rate and/or blood pressure, the treatment must be stopped. If necessary, the following antidotes can be administered, alone or in succession: Atropine IV 0.5-2 mg; orciprenaline 0.5 mg by slow IV injection; glucagon 1-5 mg may also be given.
Contraindications
Bisoprolol: Overt Cardiac Failure: In general, β-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 patients, they must be used cautiously. Cardiogenic shock, sick sinus syndrome, sinoatrial block, 2nd- or 3rd-degree atrioventricular block, considerable bradycardia (pulse slower than 50 beats/min), asthma and chronic obstructive bronchopneumopathies in their severe forms, untreated pheochromocytoma, Raynaud's disease and peripheral arterial disorders in their severe forms, hypotension, known hypersensitivity to bisoprolol and metabolic acidosis. Acute myocardial infarction, prinzmetal's angina.
Hydrochlorothiazide: Known hypersensitivity to hydrochlorothiazide or other sulfonamide derivatives, renal failure (CrCl <30 mL/min), coma and pre-coma hepaticum, severe hypokalemia or hyponatremia.
Special Precautions
Bisoprolol: Never interrupt treatment suddenly in case of ischemic heart disease. Use with care in cases of 1st-degree AV block. Since bisoprolol is a highly selective β1-adrenoreceptor blocker, it may be prescribed with care in patients with a history of chronic obstructive bronchopathy or a family history of asthma. However, an increase in airways resistance may be observed in certain patients and this may be regarded as a signal to discontinue therapy. This bronchospasm generally subsides on administration of a standard bronchodilator eg, salbutamol.
Bisoprolol has a low affinity for β2-receptors and therefore, does not cause hypoglycemia. However, caution is required in diabetics because bisoprolol may mask the symptoms of hypoglycemia (tachycardia in particular).
Beta-blockers may trigger or aggravate symptoms connected with arterial insufficiency in patients with peripheral vascular disorders. Caution is required in these patients.
In patients susceptible to a severe anaphylactic reaction, whatever its origin or during desensitizing treatments, β-blockers may lead to an aggravation of the reaction and to resistance to its treatment with adrenaline in the usual doses.
Hydrochlorothiazide: It has been observed in clinical studies that the low dose of hydrochlorothiazide present in Lodoz leads to a smaller increase in serum uric acid than that usually described after higher doses. Caution is necessary, however, in patients predisposed to gout or hyperuricemia.
The use of Lodoz with a particularly low thiazide content (6.25 mg) reduces the risk of any appreciable electrolyte imbalance. However, checks of the water and electrolyte balance must be carried out at regular intervals in all patients treated with diuretics. Thiazides can induce hypokalemia and therefore, serum potassium must be monitored, particularly in the elderly, in patients on digitalis medication, on a low-potassium diet or with gastrointestinal anomalies.
Concomitant administration with insulin or oral antidiabetics may potentiate or prolong or else attenuate their effect. Regular monitoring of blood glucose levels is therefore necessary.
Bisoprolol and Hydrochlorothiazide: Before any surgical intervention, the anesthetist must be informed of treatment with Lodoz. In patients with severe ischemic heart disease, the risks and the advantages of continuing treatment must be evaluated. Caution is required when using volatile anesthetics, associated with a risk of increased hypotension. Hydrochlorothiazide may increase the response to certain curare products.
Use in pregnancy: There are no adequate and well-controlled studies with Lodoz in pregnant women. It should be used during pregnancy only if the potential benefit justifies the risk to the fetus.
Use in lactation: Use during the lactation period is contraindicated since hydrochlorothiazide can inhibit milk production. If use during this period is essential, breastfeeding should be avoided.
Use In Pregnancy & Lactation
Use in pregnancy: There are no adequate and well-controlled studies with Lodoz in pregnant women. It should be used during pregnancy only if the potential benefit justifies the risk to the fetus.
Use in lactation: Use during the lactation period is contraindicated since hydrochlorothiazide can inhibit milk production. If use during this period is essential, breastfeeding should be avoided.
Adverse Reactions
Lodoz is well-tolerated, its side effects are for the most part attributable to its pharmacological activity.
The side effects reported for each individual constituent are as follows: Bisoprolol: Clinical: Occasionally, the following side effects are reported: Central nervous disturbances eg, tiredness, depression, dizziness, headache, asthenia, sensation of cold extremities, bradycardia, insomnia, nightmares, digestive complaints (gastralgia, nausea, vomiting), muscle and joint ache, perspiration.
In rare cases, the following have been reported: Decrease in atrioventricular conduction or intensification of existing atrioventricular block, exacerbation of heart failure, sudden fall in blood pressure, bronchospasm, aggravation of existing intermittent claudication, paresthesia, various skin manifestations, including psoriasis, lacrimation abnormality.
Hydrochlorothiazide: Clinical: Hypersensitivity reactions, anaphylactic reactions, essentially dermatological, in patients predisposed to allergic or asthmatic manifestations: Nausea, constipation, vertigo, asthenia, paresthesia, headache, rarely reported and usually requiring dose reduction; exceptional cases of pancreatitis.
Biochemical: Although the risk of hypokalemia is limited with this combination because of the very low dose of hydrochlorothiazide, serum electrolytes should be checked at regular intervals to detect any signs of water and electrolyte imbalance: Hyponatremia, hypochloremic alkalosis and hypokalemia.
Hypokalemia may occur, especially after administration of corticoids, tetracosactide or laxatives.
An increase in serum uric acid and blood glucose during treatment: The use of this diuretic in patients predisposed to gout or in diabetics should be carefully considered. Hematological disorders have been very rare, thrombocytopenia, leukopenia, agranulocytosis.
Drug Interactions
Bisoprolol: Volatile Halogenated Anesthetics: Reduction of the compensating cardiovascular reactions by β-blockers. (β-adrenergic inhibition can be lifted during the intervention by β-stimulants.) As a general rule, do not interrupt treatment with β-blockers, and in any event do not interrupt it suddenly. Inform the anesthetist of this treatment. The concurrent use of rifampicin can reduce the elimination half-life of bisoprolol, although an increase in dose is generally not necessary.
Theophylline: β-Blockers should be avoided on pharmacological grounds (bronchospasm).
Corticosteroids, NSAIDs: Antagonism of hypotensive effect.
Calcium-Channel Blockers (Bepridil, Diltiazem, Verapamil): Automatism disorders (excessive bradycardia, sinus arrest), sinoatrial and atrioventricular conduction disturbances and heart failure (synergistic effects). Such combinations should only be used with close clinical monitoring including ECGs, especially in the elderly or at the beginning of treatment.
Dihydropyridines (Combination to be Taken into Account): Hypotension, heart failure in patients with latent or uncontrolled heart failure (negative inotropic effect of dihydropyridines in vitro, possibly acting additively with the negative inotropic effect of β-blockers). The presence of the β-blocker treatment can furthermore reduce the reflex sympathetic reaction occurring in case of excessive hemodynamic repercussion.
Antiarrhythmics (Propafenone and Class 1A Drugs: Quinidine, Hydroquinidine, Disopyramide and Amiodarone): Contractility, automatism and conduction disorders (reduction of compensating sympathetic mechanisms), increased risk of myocardial depression and bradycardia.
Insulin and Sulfonamide Hypoglycemics: All β-blockers may enhance hypoglycemic effect and mask certain symptoms of hypoglycemia: Palpitations and tachycardia. Warn the patient and increase self-monitoring of blood glucose, especially at the beginning of treatment.
Lidocaine (Described for Propranolol, Metoprolol and Nadolol): Elevation of plasma lidocaine levels, with a possible increase in undesirable neurological and cardiac effects (reduction of the liver metabolism of lidocaine). Adjust the dosage of lidocaine. Clinical monitoring, ECG and possibly, monitoring of plasma lidocaine levels during and after interruption of treatment with β-blockers.
Connected with Hydrochlorothiazide: Lithium: Increased serum lithium levels with signs of overdosage, as in low-sodium regimes (reduced urinary excretion of lithium). If this combination cannot be avoided, strict surveillance of serum lithium and adaptation of the dosage are necessary.
High Doses of Salicylates: See NSAIDs.
Hyperkalemic Diuretics (Amiloride, Potassium canreonate, Spironolactone, Triamterene): Rational combination, used for certain patients, does not exclude the occurrence of hypokalemia, or particularly in cases of renal failure and in diabetics, hyperkalemia. Monitor the serum potassium possibly record an electrocardiogram (ECG) and if necessary, re-assess the treatment.
Angiotensin-Converting Enzyme (ACE) Inhibitors: Risk of a sudden fall in blood pressure and/or of acute renal failure while establishing treatment with an ACE inhibitor in cases of existing sodium depletion (particularly in patients with renal artery stenosis).
NSAIDs: Reduced antihypertensive effect (inhibition of vasodilating prostaglandins by NSAIDs and water and sodium retention in case of pyrazole NSAIDs). Acute renal failure in dehydrated patients (reduced glomerular filtration). Hydration of the patient: Monitoring of renal function at the beginning of treatment.
Imipramine Antidepressants (Tricyclic Antidepressants): Antihypertensive effect and increased risk of orthostatic hypotension (additive effect).
Storage
Store below 30°C.
MIMS Class
ATC Classification
C07BB07 - bisoprolol and thiazides ; Belongs to the class of selective beta-blocking agents in combination with thiazides. Used in the treatment of cardiovascular diseases.
Presentation/Packing
FC tab 2.5 mg x 30's. 5 mg x 30's.
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