Besicor

Dosage Form & Strength

The dosage should be individually adjusted. It is recommended to start with 5 mg per day. The usual dose is 10 mg once daily with a maximum recommended dose of 20mg per day.

Dosage in Special Population

Bisoprolol is not recommended during pregnancy unless clearly necessary. Breastfeeding is not recommended during administration of bisoprolol. Patients with renal impairment In patients with severe renal impairment (creatinine clearance < 20 ml/min) the dose should not exceed 10 mg once daily. This dosage may eventually be divided into halves. Patients with severe liver impairment No dosage adjustment is required, however careful monitoring is advised.

Indications

Besicor 2.5 / 5 is indicated for the treatment of hypertension

Adverse Effects

Common bisoprolol side effects may include headache; feeling tired; sleep problems (insomnia); joint pain; swelling; or cold symptoms such as stuffy nose, runny nose, cough, sore throat.

Drug Interactions

Bisoprolol:Should not be combined with other beta-blocking agents. Patients receiving catecholaminedepleting drugs, such as reserpine or guanethidine, should be closely monitored, because the added betaadrenergic blocking action of Bisoprolol may produce excessive reduction of sympathetic activity. In patients receiving concurrent therapy with clonidine, if therapy is to be discontinued, it is suggested that Bisoprolol be discontinued for several days before the withdrawal of clonidine. Bisoprolol should be used with care 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. Concurrent use of rifampin increases the metabolic clearance of Bisoprolol, resulting in a shortened elimination half-life of Bisoprolol. However, initial dose modification is generally not necessary. Pharmacokinetic studies document no clinically relevant interactions with other agents given concomitantly, including thiazide diuretics and cimetidine. There was no effect of Bisoprolol on prothrombin time in patients on stable doses of warfarin. Risk of Anaphylactic Reaction: While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reactions.

Mechanism of Action

Bisoprolol is a highly beta1-selective-adrenoceptor blocking agent, lacking intrinsic sympathomimetic and relevant membrane stabilising 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 the airway resistance and beta2-mediated metabolic effects. Its beta1-selectivity extends beyond the therapeutic dose range

Pharmacokinetics

Bisoprolol Bisoprolol is absorbed almost completely from the gastrointestinal tract. Together with the very small first pass effect in the liver, this results in a high bioavailability of approximately 90%. The plasma protein binding of bisoprolol is about 30 %. The distribution volume is 3.5 l/kg. The total clearance is approximately 15 l/h. The plasma elimination half-life (10-12 hours) provides 24 hours efficacy following a once daily dosage. Bisoprolol is excreted from the body by two routes, 50 % is metabolised by the liver to inactive metabolites which are then excreted by the kidneys. The remaining 50 % is excreted by the kidneys in an unmetabolised form. Since elimination takes place in the kidneys and the liver to the same extent a dosage adjustment is not required for patients with impaired liver function or renal insufficiency. In patients with chronic heart failure (NYHA stage III) the plasma levels of bisoprolol are higher and the half life is prolonged compared to healthy volunteers. Maximum plasma concentration at steady state is 64±21 ng/ml at a daily dose of 10 mg and the half life is 17±5 hours.

Drug Use in Pregnancy

Bisoprolol: Pregnancy: Bisoprolol has pharmacological effects that may cause harmful effects on pregnancy and/or the fetus/newborn. In general, beta-adrenoceptor blockers reduce placental perfusion, which has been associated with growth retardation, intrauterine death, abortion or early labour. Adverse effects (e.g. hypoglycaemia and bradycardia) may occur in the fetus and newborn infant. If treatment with beta-adrenoceptor blockers is necessary, beta1-selective adrenoceptor blockers are preferable. Bisoprolol is not recommended during pregnancy unless clearly necessary. If treatment with bisoprolol is considered necessary, the uteroplacental blood flow and the fetal growth should be monitored. In case of harmful effects on pregnancy or the fetus alternative treatment should be reccomended. The newborn infant must be closely monitored. Symptoms of hypoglycaemia and bradycardia are generally to be expected within the first 3 days. Breastfeeding: There are no data on the excretion of bisoprolol excreted in human milk. Therefore, breastfeeding is not recommended during administration of bisoprolol.

Drug Use in Renal Impairment

Renal Impairement: There is no information regarding pharmacokinetics of bisoprolol in patients with chronic heart failure and with impaired hepatic or renal function. Uptitration of the dose in these populations should therefore be made with additional caution.

Drug Use in Hepatic Impairment

Hepatic Impairement: There is no information regarding pharmacokinetics of bisoprolol in patients with chronic heart failure and with impaired hepatic or renal function. Uptitration of the dose in these populations should therefore be made with additional caution.

Drug Use in Pediatric Population

Paediatric population There is no paediatric experience with bisoprolol, therefore its use cannot be recommended for children.

Drug Use in Geriatric Population

Bisoprolol: Elderly No dosage adjustment is normally required.