1.TOPROL XL HISTORY
(How was Toprol XL discovered?)

Toprol XL is a product of Astra-Zeneca International. 

The US FDA approved Toprol XL in February 2001.  

Note: World-drugs.net sells generic version of Toprol XL

2.TOPROL XL FACTS

Astra-Zeneca is one of the world's leading pharmaceutical companies with 60,000 people - 12,000 in the US alone - dedicated to the discovery, development, and marketing of new pharmaceutical solutions, to enrich the quality of people's lives all over the world.

The focused areas of research include:

• Cardiovascular
• Gastrointestinal
• Infection
• Neuroscience
• Oncology
• Respiratory

Astra-Zeneca discovers new medicines that are designed to improve the health and quality of life of patients around the world - medicines which are innovative, effective and which offer added benefits such as reduced side effects or better ways of taking the treatment. Astra-Zeneca also focuses on getting the best from every medicine they make by exploring all the ways it can be used or improved.

At AstraZeneca, innovation is about more than just research. 

3.ABOUT TOPROL XL MEDICATION

What is High Blood Pressure (Hypertension)?

High blood pressure, also known as hypertension, is a serious disease affecting your heart and blood vessels. It occurs when the blood exerts too much pressure against the walls of the blood vessels. In fact, that is what the term hypertension means: "too much" (hyper) "pressure" (tension). It affects upwards of 58 million people nationwide.

 

High blood pressure is serious because it places you at risk for certain life threatening and disabling conditions. If left untreated, High blood pressure could lead to heart attack, kidney disease, and/or stroke.

This happens because as your blood continuously exerts too much pressure against the walls of the blood vessels, it places extra stress on the heart and blood vessels.

Blood pressure is measured in two numbers, systolic (top or higher number) and diastolic (lower number). The higher number is the maximum pressure, which occurs when the heart beats (systole), and the lower number is the lowest pressure measured when the heart relaxes between beats (diastole), just before the next contraction. A systolic reading of 140 or greater and a diastolic reading of 90 or greater is considered high.

The normal blood pressure is less than 120/80. In fact, for every 20/10 increase in blood pressure, your risk of cardiovascular events, such as heart attack or stroke, is DOUBLED.

 

Symptoms of High Blood Pressure

High blood pressure is sometimes called the "silent killer" because the symptoms are rarely seen or felt. So, even though it might be upsetting to be told that you have High blood pressure, it's good that your doctor has discovered it. Treatment can help avoid the serious, long-term effects of High blood pressure.

What are antihypertensives?
Antihypertensives are medications used to treat high blood pressure (hypertension). Although some patients do not need to take medication to control their High blood pressure, anyone who is prescribed medication needs to take it exactly as prescribed to avoid the serious medical problems associated with the condition. People taking Antihypertensives are also encouraged to make healthy lifestyle changes, such as quitting smoking, losing weight and getting regular exercise. Furthermore, they are encouraged to speak with their physician before taking any prescription medications, such as narcotics, or over-the-counter medications, such as diet pills.

Finally, people with High blood pressure are urged to be patient as the type and level of their medication are adjusted for optimal results. This is especially important because the vast majority of patients have no symptoms, making hypertension the silent killer.

There are a wide variety of Antihypertensives and combinations of different medications that are available, and it may take some time before the ideal treatment has been found and finely tuned to the patients needs.

Antihypertensives include:

Diuretics ("water pills")
Diuretics are sometimes called "water pills" because they work in the kidney and flush excess water and sodium from the body.

Beta Blockers
Beta-blockers reduce nerve impulses to the heart and blood vessels. This makes the heart beat slower and with less force. Blood pressure drops and the heart works less hard.

Alpha Blockers
Alpha-blockers reduce nerve impulses to blood vessels, which allows blood to pass more easily, causing the blood pressure to go down.

Alpha-Beta Blockers
Alpha-beta-blockers work the same way as alpha-blockers but also slow the heartbeat, as beta-blockers do. As a result, less blood is pumped through the vessels and the blood pressure goes down.

Nervous System Inhibitors
Nervous system inhibitors relax blood vessels by controlling nerve impulses. This causes the blood vessels to become wider and the blood pressure to go down.

Angiotensin Converting Enzyme (ACE) Inhibitors
Angiotensin converting enzyme (ACE) inhibitors prevent the formation of a hormone called angiotensin II, which normally causes blood vessels to narrow. The ACE inhibitors cause the vessels to relax and blood pressure goes down.

Calcium Channel Blockers

CCBs keep calcium from entering the muscle cells of the heart and blood vessels. This causes the blood vessels to relax and pressure goes down.

Angiotensin Receptor Blockers (formal medical name angiotensin-2-receptor antagonists, known as "sartans" for short). These agents are sometimes prescribed together, for instance an ACE inhibitor along with a calcium channel blocker.

Angiotensin antagonists shield blood vessels from angiotensin II. As a result, the vessels become wider and blood pressure goes down.

Some common beta-blockers include:

• Acebutolol
• Atenolol
• Betaxolol
• Bisoprolol
• Carteolol
• Metoprolol
• Nadolol
• Penbutolol
• Pindolol
• Propranolol
• Timolol

Toprol XL
Toprol XL is a beta-adrenergic blocking agent.

Toprol XL blocks the action of the sympathetic nervous system, a portion of the involuntary nervous system. The sympathetic nervous system stimulates the pace of the heartbeat. By blocking the action of these nerves, Toprol XL reduces the heart rate and is useful in treating abnormally rapid heart rhythms. 

4.TOPROL XL EFFECTIVENESS
When is Toprol XL best taken?

The plasma levels following administration of Toprol XL dose are characterized by lower peaks, longer time to peak and significantly lower peak to trough variation. The peak plasma levels following once daily administration of Toprol XL dose average one-fourth to one-half the peak plasma levels obtained following a corresponding dose of conventional metoprolol, administered once daily or in divided doses of Toprol XL. At steady state the average bioavailability of metoprolol following administration of Toprol XL, across the dosage range of 50 to 400 mg once daily, was 77% relative to the corresponding single or divided doses of conventional metoprolol. Nevertheless, over the 24 hour dosing interval, b1-blockade is comparable and dose- related. The bioavailability of metoprolol shows a dose-related, although not directly proportional increase with dose and is not significantly affected by food following Toprol XL administration.

5.TOPROL XL EFFECTS ON SPECIAL POPULATION
How do different people react to Toprol XL?

Toprol XL has been shown to increase post-implantation loss and decrease neonatal survival in rats at doses up to 55.5 times the maximum daily human dose of 450 mg. Distribution studies in mice confirm exposure of the fetus when Toprol XL is administered to the pregnant animal. These studies have revealed no evidence of impaired fertility or teratogenicity. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. 

Nursing Mothers
Toprol XL is excreted in breast milk in very small quantities. An infant consuming 1 liter of breast milk daily would receive a dose of less than 1 mg of the drug. Caution should be exercised when Toprol XL is administered to a nursing woman.

Pediatric Use
Safety and effectiveness in children have not been established.

6.TOPROL XL EFFECTS ON MEDICAL CONDITIONS
(How does Toprol XL affect your existing condition/ailment?)

Cardiac Failure:

Sympathetic stimulation is a vital component supporting circulatory function in congestive heart failure, and beta-blockade carries the potential hazard of further depressing myocardial contractility and precipitating more severe failure. In hypertensive and angina patients who have congestive heart failure controlled by digitalis and diuretics, Toprol XL should be administered cautiously. Both digitalis and Toprol XL slow AV conduction.

In Patients Without a History of Cardiac Failure:

Continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure. At the first sign or symptom of impending cardiac failure, patients should be fully digitalized and/or given a diuretic. The response should be observed closely. If cardiac failure continues, despite adequate digitalization and diuretic therapy Toprol XL should be withdrawn.

Ischemic Heart Disease:

Following abrupt cessation of therapy with certain beta-blocking agents, exacerbations of angina pectoris and, in some cases, myocardial infarction have occurred. When discontinuing chronically administered Toprol XL, particularly in patients with ischemic heart disease, the dosage should be gradually reduced over a period of 1-2 weeks and the patient should be carefully monitored. If angina markedly worsens or acute coronary insufficiency develops, Toprol XL administration should be reinstated promptly, at least temporarily, and other measures appropriate for the management of unstable angina should be taken. Patients should be warned against interruption or discontinuation of therapy without the physician's advice. Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue Toprol XL therapy abruptly even in patients treated only for hypertension. 

Bronchospastic Diseases:

PATIENTS WITH BRONCHOSPASTIC DISEASES SHOULD, IN GENERAL, NOT RECEIVE BETA-BLOCKERS. Because of its relative beta1-selectivity, however, Toprol XL may be used with caution in patients with bronchospastic disease who do not respond to, or cannot tolerate, other antihypertensive treatment. Since beta1- selectivity is not absolute, a beta2-stimulating agent should be administered concomitantly, and the lowest possible dose of Toprol XL should be used.

Major Surgery:

The necessity or desirability of withdrawing beta-blocking therapy prior to major surgery is controversial; the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures. 

Toprol XL like other beta-blockers, is a competitive inhibitor of beta-receptor agonists, and its effects can be reversed by administration of such agents, e.g., dobutamine or isoproterenol. However, such patients may be subject to protracted severe hypotension. Difficulty in restarting and maintaining the heart beat has also been reported with beta- blockers.

Diabetes and Hypoglycemia:

Toprol XL should be used with caution in diabetic patients if a beta-blocking agent is required. Beta- blockers may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be significantly affected.

Thyrotoxicosis:

Beta-adrenergic blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-blockade, which might precipitate a thyroid storm. 

7.OTHER/ALTERNATE USES OF TOPROL XL
(What else does Toprol XL treat?)

Toprol XL also reduces the force of heart muscle contraction and lowers blood pressure. By reducing the heart rate and the force of muscle contraction, Toprol XL reduces heart muscle oxygen demand. Since angina occurs when oxygen demand of the heart exceeds supply, Toprol XL is helpful in treating angina.

8.ADVERSE/SIDE EFFECTS of TOPROL XL
What are the side effects of Toprol XL?

Hypertension and Angina
Most adverse effects have been mild and transient. The following adverse reactions have been reported for Toprol XL.

Central Nervous System:

Tiredness and dizziness have occurred in about 10 of 100 patients. Depression has been reported in about 5 of 100 patients. Mental confusion and short-term memory loss have been reported. Headache, somnolence, nightmares, and insomnia have also been reported.

Cardiovascular:

Shortness of breath and bradycardia have occurred in approximately 3 of 100 patients. Cold extremities; arterial insufficiency, usually of the Raynaud type; palpitations; congestive heart failure; peripheral edema; syncope; chest pain; and hypotension have been reported in about 1 of 100 patients.

Respiratory:

Wheezing (bronchospasm) and dyspnea have been reported in about 1 of 100 patients.

Gastrointestinal:

Diarrhea has occurred in about 5 of 100 patients. Nausea, dry mouth, gastric pain, constipation, flatulence, digestive tract disorders and heartburn have been reported in about 1 of 100 patients.

Hypersensitive Reactions:

Pruritus or rash have occurred in about 5 of 100 patients. Worsening of psoriasis has also been reported.

Miscellaneous:

Peyronie's disease has been reported in fewer than 1 of 100,000 patients. Musculoskeletal pain, blurred vision, decreased libido and tinnitus have also been reported.

There have been rare reports of reversible alopecia, agranulocytosis, and dry eyes. Discontinuation of the drug should be considered if any such reaction is not otherwise explicable. The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with Toprol XL.

Potential Adverse reactions

A variety of adverse reactions not listed above have been reported with other beta-adrenergic blocking agents and should be considered potential adverse reactions to extended release metoprolol succinate.

Central Nervous System:

Reversible mental depression progressing to catatonia; an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance on neuropsychometrics.

Cardiovascular:

Intensification of AV block.

Hematologic:

Agranulocytosis, nonthrombocytopenic purpura, thrombocytopenic purpura.

Hypersensitive Reactions:

Fever combined with aching and sore throat, laryngospasm, and respiratory distress.