Conguard

Conguard

Conguard

Cardiovascular Drugs

-Conguard® is a B1-selective (cardioselective) adrenoreceptor blocking agent

without significant membrane stabilizing activity or intrinsic sympathomimetic

activity in its therapeutic dosage range.

Cardioselectivity is not absolute, however, and at higher doses  (>/=20mg),

bisoprolol fumarate also inhibits B2- adrenoreceptors, chiefly located in the

bronchial and vascular musculature; to retain selectivity, it is therefore important to

use the lowest effective dose.

-The absolute bioavailability after a 10mg oral dose of bisoprolol fumarate is about

80%.

-Absorption is not affected by the presence of food.

-The first pass metabolism of bisoprolol fumarate is about 20%.

-Binding to serum proteins is approximately 30%. Bisoprolol shows linear kinetics

and the plasma concentrations are proportional to the administered dose over the

dose range 5 to 20 mg.Peak plasma concentration occur within (2 - 3) hours of

dosing with 5 to 20 mg.

-The half-life of bisoprolol in plasma is ranging between 10- 12 hours.

-It is metabolised in the liver. Approximately 50% of an orally administered dose is

excreted in urine as unchanged drug and the remains appearing in the form of

inactive metabolites. In subjects with creatinine clearance < 40 ml/min, the plasma

half-life is increased approximately threefold compared to healthy subjects.

-In subjects with cirrhosis of the liver, the elimination of Conguard® is more

variable in rate and slower than that in healthy subjects. In normal volunteers

bisoprolol therapy resulted in a reduction of exercise, and isoproterenol-induced

tachycardia. The maximal effect occurred within (1- 4) hours post-dosing. Effects

persisted for 24 hours at doses equal to or greater than 5 mg.

Indecation

Conguard® is indicated for the treatment of:

-High blood pressure (hypertention).

-Coronary heart disease (angina pectoris).

-Stable chronic, moderate to severe heart failure (myocardial insufficiency) with

impaired systolic ventricular function (ejection fraction ≤35%, determined by

echocardiography) in addition to ACE inhibitors and diuretics, and optionally

cardiac glycosides.

Dosage & Administration

Conguard® should be taken as a whole with some liquid in the morning before,

during or after breakfast once daily. In all cases the dose regimen is adjusted

individually by doctor.

Hypertension | Angina :

The usual initial dose is 5 mg bisoprolol. If necessary, the dose may be increased to

10 mg bisoprolol.  The maximum recommended dose is 20 mg bisoprolol once daily.

Adjunct in heart failure :

Adult: Initially 1.25 mg once daily for 1 week, dose to be taken in the morning, then

increased if tolerated to 2.5 mg once daily for 1 week, then increased if tolerated to

3.75 mg once daily for 1 week, then increased if tolerated to 5 mg once daily for 4

weeks, then increased if  tolerated to 7.5 mg once daily for 4 weeks, then increased

if tolerated to 10 mg once daily; maximum 10 mg daily.

-In patients with liver or kidney function disorders of mild to moderate severity no

dosage adjustment is normally required. In patients with severe renal impairment

(creatinine clearance < 20 ml/min) and in patients with severe hepatic impairment a

daily dose of 10 mg bisoprolol must not be exceeded.

- Each film-coated tablet of Conguard contains  

  Bisoprolol fumarate                          5 mg

Conguard® must not be taken in:

-Acute heart failure or during episodes of heart failure decompensation requiring

intravenous therapy with substances increasing the contractility of the heart; Shock

induced by disorders of cardiac function (cardiogenic shock); Severe disturbances of

atrioventricular conduction (second or third degree AV block) without a pacemaker;

Sick sinus syndrome; Sinoatrial block; Slowed heart rate, causing symptom

bradycardia; Decreased blood pressure, causing symptoms; Severe bronchial

asthma; Severe forms of peripheral arterial occlusive disease or Raynaud’s

syndrome; Untreated tumours of the adrenal gland (phaeochromocytoma);

Metabolic acidosis; Hypersensitivity to bisoprolol or to any of the excipients

Combinations not recommended in treatment of stable chronic heart failure:

-Class-I antiarrhythmic medicines (e.g. quinidine, disopyramide, lidocaine,

phenytoin; flecainide, propafenone) may increase the depressant effect of

Conguard® on atrio-ventricular impulse conduction and the contractility of the

heart.

Combinations not recommended in all indications:

-Calcium antagonists of the verapamil type and to a lesser extent of the diltiazem

type may lead to reduced contractility of the heart muscle and delayed

atrio-ventricular impulse conduction when used with Conguard®.

-Centrally acting blood pressure-lowering medicines (such as clonidine,

methyldopa, moxonodine and rilmenidine) may lead to a reduction of heart rate and

cardiac output, as well as to vasodilation due to a decrease in the central

sympathetic tonus. Abrupt withdrawal, particularly if prior to beta-blocker

discontinuation, may increase risk of “rebound hypertension”.

Combinations to be used with caution in treatment of hypertension or coronary

heart disease (angina pectoris):

-Class-I antiarrhythmic medicines (e.g. quinidine, disopyramide, lidocaine,

phenytoin; flecainide, propafenone) may increase the depressant effect of

Conguard® on atrio-ventricular impulse conduction and the contractility of the

heart.

Combinations to be used with caution in all indications

-Calcium antagonists of the dihydropyridine type (e.g. Nifedipine, felodipine,

amlodipine) may increase the risk of hypotension when used with Conguard®. An

increased risk of a further deterioration of the ventricular pump function in patients

with heart failure cannot be excluded.

-Class-III antiarrhythmic medicines (e.g. amiodarone) and Parasympathomimetic

medicines may increase the inhibitory effect of Conguard® on atrio-ventricular

impulse conduction.

-Topical ß-blockers (e.g. eye drops for glaucoma treatment) may add to the systemic

effects of Conguard®.

-The blood sugar lowering effect of insulin or oral antidiabetic medicines may be

increased. Warning signs of reduced blood glucose (hypoglycaemia) – especially

accelerated heart rate (tachycardia)- may be masked or suppressed. Such

interactions are considered to be more likely with nonselective ß-blockers.

-Anaesthetic agents may increase the risk of cardiodepressive actions of

Conguard®, leading to hypotension.

-Digitalis may lead to an increase in impulse conduction time and thus reduction in heart rate.

-NSAIDs may reduce the blood pressure-lowering effect of Conguard®.

-ß-Sympathomimetics (e.g. isoprenaline, dobutamine) when used with Conguard® may lead to a reduced effect of both agents.

-A combination of Conguard® with sympathomimetics that activate both ß- and α-adrenoceptors (e.g. noradrenaline, adrenaline) may intensify the α-adrenoceptor-

mediated vasoconstrictor effects of these agents leading to blood pressure increase.

-Tricyclic antidepressants, barbiturates, phenothiazines may increase the blood pressure lowering effect of Conguard®.

Combinations to be considered:

-Mefloquine may increase the risk of decelerating the heart rate (bradycardia), if used with Conguard®.

-Monoamine oxidase inhibitors (except MAO-B inhibitors) may enhance the hypotensive effect of the  beta-blockers. Concomitant use may also be a risk for

hypertensive crisis.

-During pregnancy Conguard® is only recommended following careful

assessment of benefit-to-risk ratio by the doctor.

-In general, beta-blockers reduce placental blood flow and may affect the

development of the unborn child.

- There are no data on the excretion of bisoprolol in human breast milk or the safety

of bisoprolol exposure in infants. Therefore administration of Conguard® is not

recommended during breastfeeding.

Conguard® may cause side effects as following :

-Very common:bradycardia (in patients with chronic heart failure),

-Common: worsening of pre-existing heart failure (in patients with chronic heart

failure), dizziness, headache, gastrointestinal complaints such as nausea, vomiting,

diarrhoea, constipation, feeling of coldness or numbness in the extremities,

hypotension especially in patients with heart failure, asthenia (in patients with

chronic heart failure), fatigue.

-Uncommon: AV-conduction disturbances; bradycardia (in patients with

hypertension or angina pectoris); worsening of pre-existing heart failure (in patients

with hypertension or angina pectoris), bronchospasm in patients with bronchial

asthma or a history of obstructive airways disease, muscle weakness, muscle

cramps, asthenia (in patients with hypertension or angina pectoris), depression,

sleep disorder.

-Rare: increased triglycerides, increased liver enzymes (ALAT, ASAT), reduced

tear flow (to be considered if the patient uses contact lenses), hearing disorders,

allergic rhinitis, hypersensitivity reactions such as pruritus, flush, rash, hepatitis,

erectile dysfunction, nightmare, hallucination, potency disorrder.

-Very Rare: conjunctivitis, alopecia. Beta-blockers may provoke or worsen

psoriasis or induce psoriasis-like rash.

Overdose

-The most frequent signs of Conguard® overdose include slow heart rate

(bradycardia), marked drop in blood pressure, acute heart failure, hypoglycaemia

and bronchospasm.

-In general, if overdose occurs, bisoprolol treatment is stopped and supportive and

symptomatic treatment is provided. Limited data suggest that bisoprolol is hardly dialysable.

The following section describes when Conguard® must be used with special

caution:

-Diabetes mellitus with extremely fluctuating blood glucose levels: symptoms of

markedly reduced blood glucose (hypoglycaemia) such as tachycardia, palpitations

or sweating can be masked.

-Strict fasting. 

-Ongoing desensitisation therapy.

-Mild disturbances of atrioventricular conduction (first degree AV block).

-Disturbed blood flow in the coronary vessels due to vasospasms ( prinzmetals

angina).

-Peripheral arterial occlusive disease (aggravation of symptoms may occur 

especially when starting therapy).

-Patients with psoriasis or with a personal history of psoriasis.

-In bronchial asthma or other symptomatic chronic obstructive pulmonary diseases,

which may cause symptoms, concomitant bronchodilating therapy is recommended.

-Allergic reactions: Conguard®, may increase the sensitivity to allergens and the

severity of anaphylactic reactions.

-In patients undergoing general anaesthesia the anaesthetist must be aware of

beta-blockade.

-In patients with a tumour of the adrenal gland (phaeochromocytoma) Conguard®

may only be administered after previous alphareceptor blockade.

-Under treatment with Conguard® the symptoms of a thyroid hyperfunction

(thyrotoxicosis) may be masked.

-There is insufficient experience with bisoprolol in children, therefore the use of

Conguard® cannot be recommended for children.

-Conguard® 5 : Blister of 10 tablets, packs of 2 blisters .

-Conguard® 2.5 : Blister of 10 tablets, packs of 2 blisters .

-Store in a dry place at a temperature not exceeding 25 ºC.