Concor 10

Concor 10 which contains the salt Bisoprolol 10 mg is a cardioselective beta-1 adrenergic blocking agent belonging to the beta-blocker class and is approved for use in the following clinical indications.

• High Blood Pressure: Beta-blocking medications' antihypertensive effects still lack a precise mechanism of action. However, several potential methods have been put forth: reduced cardiac output due to competing antagonistic interactions between catecholamines at peripheral adrenergic neuron locations, decreased sympathetic outflow to the periphery due to a significant influence; and suppression of renin activity.

Although not approved, there have been certain Off-label uses documented for Concor 10 . These include:

• Angina Pectoris: Concor 10 is helpful in the treatment of angina pectoris because it lowers the oxygen demands of the heart at any given amount of effort.
• Migraine: Beta-blockers alleviate that pain by making the blood vessels relax so that the blood can flow normally.
• Myocardial Infarction: Beta-blockers reduce myocardial workload, and thus oxygen demand, via a reduction in heart rate and blood pressure. They reduce catecholamine levels, decrease myocardial ischemia and limit infarct size, and may prevent the development of definite infarction in acute coronary syndrome (ACS) patients.
• Atrial fibrillation: Beta-blockers reduce the heart rate by limiting the effects of adrenaline and other related hormones on the heart. In the treatment of arrhythmia, beta-blockers are mainly used to regulate the heart rate. However, beta-blockers are also known as drugs with an antiarrhythmic effect due to the suppression of sympathetic activity. Regardless of whether a rhythm or rate control method is used, beta blockers are typically the first line of treatment for AF.

Concor 10 which contains the salt Bisoprolol 10 mg is a cardioselective beta-1 adrenergic blocking agent belonging to the beta-blocker class and is available in the form of tablets.

High Blood Pressure: Bisoprolol is administered only orally as 2.5- 5 mg tablets once daily, which may increase to 10 mg and if necessary to 20 mg orally once/day.

Concor 10 has low lipophilicity, so it does not cross the blood-brain barrier with a high amount. Concor 10 has a long half-life that extends from 9 to 12 hours.

It also has high bioavailability, reaching 80 % compared to most beta-blockers with lower bioavailability since they have high first-pass metabolism in the liver.

Heart Failure: Bisoprolol is administered 1.25mg orally once/day; increased gradually, if necessary, not to exceed 10 mg/day

Concor 10 which contains the salt Bisoprolol 10 mg should be used in the treatment of high blood pressure, angina pectoris, migraine, and acute myocardial infarction along with appropriate dietary restrictions.

• High Blood Pressure: It has been observed that the low-salt Dietary Approach to Stop Hypertension (DASH) diet lowers blood pressure. Sometimes after a few weeks, its effects on blood pressure become noticeable.
• Angina Pectoris: Avoid foods that are high in saturated fat and hydrogenated or partially hydrogenated fats. Reduce your intake of dairy products including cheese, cream, and eggs.
• Migraine: Some commonly triggered diets include: Baked food with yeast, such as sourdough bread, bagels, doughnuts, coffee cake, Chocolate, Cultured dairy products (like yogurt and kefir), Tomatoes, Vegetables like onions, pea pods, some beans, corn, and sauerkraut, Vinegar and Alcohol must be avoided.
• Myocardial infarction: No more than 25 to 35 percent of your daily calories should come from total fat (including saturated fat).

Less than 7 %of your daily calories should come from saturated fat. Avoid trans fats and Consume less than 200 milligrams a day of dietary cholesterol.

The dietary restriction should be individualized as per patient requirements.

• Cardiac Failure

Sympathetic stimulation is an important component supporting circulatory function in the setting of congestive heart failure, and beta-blockade may result in further depression of myocardial contractility and precipitate more severe failure. 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 them. In such a situation, they must be used cautiously.

• In Patients Without a History of Cardiac Failure:

Continued depression of the myocardium with beta-blockers can, in some patients, precipitate cardiac failure. At first signs or symptoms of heart failure, discontinuation of Concor 10 should be considered. In some cases, beta-blocker therapy can be continued while heart failure is treated with other drugs.

• Abrupt Cessation of Therapy:

Exacerbation of angina pectoris and, in some instances, myocardial infarction or ventricular arrhythmia, have been observed in patients with coronary artery disease following abrupt cessation of therapy with beta-blockers. Such patients should, therefore, be cautioned against the interruption or discontinuation of therapy without the physician's advice. Even in patients without overt coronary artery disease, it may be advisable to taper therapy with Concor 10 over approximately one week with the patient under careful observation. If withdrawal symptoms occur, Concor 10 therapy should be reinstituted, at least temporarily.

• Peripheral Vascular Disease:

Beta-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease. Caution should be exercised in such individuals.

• Bronchospastic Disease

Patients with bronchospastic disease should, in general, not receive beta-blockers. Because of its relative beta1-selectivity, however, Concor 10 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 Concor 10 should be used, with therapy starting at 10 mg. A beta2 agonist (bronchodilator) should be made available.

• Anesthesia and Major Surgery

If Concor 10 treatment is to be continued perioperatively, particular care should be taken when anesthetic agents which depress myocardial function, such as ether, cyclopropane, and trichloroethylene, are used.

• Diabetes and Hypoglycemia

Beta-blockers may mask some of the manifestations of hypoglycemia, particularly tachycardia. 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 CONCOR 10 . However, patients subject to spontaneous hypoglycemia, or diabetic patients receiving insulin or oral hypoglycemic agents, must be cautioned about these possibilities, and Concor 10 fumarate should be used with caution.

• Thyrotoxicosis

Beta-adrenergic blockade may mask clinical signs of hyperthyroidism, such as tachycardia. Abrupt withdrawal of beta-blockade may be followed by an exacerbation of the symptoms of hyperthyroidism or may precipitate a thyroid storm.

PRECAUTION:

• Applies only to hypertension or angina pectoris:

Concor 10 must be used with caution in patients with hypertension or angina pectoris and accompanying heart failure.

• Applies only to chronic heart failure:

There is no therapeutic experience of Concor 10 in treating heart failure in patients with the following diseases and conditions:

• Insulin-dependent diabetes mellitus (type I)
• Severely impaired renal function
• Severely impaired hepatic function
• Restrictive cardiomyopathy
• Congenital heart disease
• Hemodynamically significant organic valvular disease
• Myocardial infarction within 3 months.

Most adverse effects have been mild and transient.

• Common Adverse effects:

Reversible mental depression progressing to catatonia; an acute reversible syndrome characterized by the disorientation of time and place; short-term memory loss; emotional lability with slightly clouded sensorium; and decreased performance on a neuro-psychometrist.

• Infrequent adverse effects:

Mesenteric arterial thrombosis, ischemic colitis, fever, combined with an aching and sore throat, laryngospasm, and respiratory distress.

• Rare adverse effect:

Erythematous rash.

• Miscellaneous:

There have been reports of skin rashes and dry eyes associated with the use of beta-adrenergic blocking drugs.

The clinically relevant drug interactions of Concor 10 which contains the salt Bisoprolol 10 mg are briefly summarized as follows:

• Concor 10 should not be combined with the other beta-blocking agents. Patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, should be closely monitored because added beta-adrenergic blocking action of Concor 10 may produce an excessive reduction of sympathetic activity.
• In patients receiving concurrent therapy with clonidine, if therapy is to be discontinued, it is suggested that Concor 10 be discontinued for several days before the withdrawal of clonidine. Concor 10 should be used with care when myocardial depressants or inhibitors of AV conduction, such as certain calcium antagonists (particularly of the phenylethylamine [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 Concor 10 , resulting in a shortened elimination half-life of Concor 10 .
• 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 Concor 10 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 challenges, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reactions.

Pharmacodynamics

The most prominent effect of Concor 10 which contains the salt Bisoprolol 10 mg is the negative chronotropic effect, resulting in a reduction in resting and exercise heart rate. There is a fall in resting and exercise cardiac output with little observed change in stroke volume, and only a small increase in right atrial pressure, or pulmonary capillary wedge pressure at rest or during exercise.

Findings in short-term clinical hemodynamics studies with Concor 10 are similar to those observed with other beta-blocking agents.

The mechanism of action of its antihypertensive effects has not been completely established. Factors that may be involved include:

1. Decreased cardiac output,

2. Inhibition of renin release by the kidneys,

3. Diminution of tonic sympathetic outflow from the vasomotor centers in the brain.

The most prominent effect of Concor 10 fumarate is the negative chronotropic effect, resulting in a reduction in resting and exercise heart rate. There is a fall in resting and exercise cardiac output with little observed change in stroke volume and only a small increase in right atrial pressure, or pulmonary capillary wedge pressure at rest or during exercise.

Pharmacokinetics

• Absorption:

Concor 10 is well absorbed in the gastrointestinal tract. The AUC is 642.87 g.hr/mL, and the bioavailability of Concor 10 is about 90% due to the minimal first pass effects. Absorption is unaffected by food intake. Peak plasma concentrations of Concor 10 are attained within 2-4 hours and steady-state concentrations are achieved within 5 days of administration. In a pharmacokinetic study, the mean peak concentration of Concor 10 was 52 micrograms/L. Cmax at steady-state concentrations of Concor 10 is 64±21 ng/ml administered at 10 mg daily.

• Distribution:

The volume of distribution of Concor 10 is 3.5 L/kg. The mean volume of distribution was found to be 230 L/kg in heart failure patients, which was similar to the volume of distribution in healthy patients. Concor 10 is known to cross the placenta.

• Metabolism:

About 50% of a single Concor 10 dose is metabolized mainly by the enzyme CYP3A4 to inactive metabolites.

• Elimination:

Concor 10 is eliminated equally by both renal and hepatic pathways. About 50% of an oral dose is excreted and remained unchanged in the urine, with the remainder of the dose excreted as inactive Concor 10 metabolites. Under 2% of the ingested dose is found to be excreted in the feces.