ASTRAZENECA BETALOC Metoprolol Succinate Sustained-release Tablets For Hypertension 95mg*7

[Drug Name]
Generic Name: Metoprolol Succinate Sustained-Release Tablets
Trade Name: Betaloc Metoprolol Succinate Sustained-Release Tablets, 95mg x 7 tablets
Pinyin Code: BeiTaLeKe ZuoZuoSuanMeiTuoLuoErHuanShiPian

[Main Ingredient]
The main ingredient of this product is metoprolol succinate.

[Properties]
This product is a white or off-white film-coated tablet. It appears white after removal of the coating.

[Indications/Main Functions]
Hypertension. Angina pectoris. Stable chronic heart failure with symptoms of left ventricular systolic dysfunction.

[Precautions]
Metoprolol may aggravate symptoms of peripheral vascular disorders, such as intermittent claudication. Caution is advised in patients with severe renal impairment, acute conditions associated with metabolic acidosis, and when used in combination with digitalis. Patients with Prinzmetal's angina may experience increased frequency and severity of angina attacks after taking beta-blockers due to alpha-receptor-mediated coronary vasoconstriction. Therefore, non-selective beta-blockers should not be used in such patients. Selective beta-1 blockers should also be used with caution. Patients with bronchial asthma or other chronic obstructive pulmonary disease should also receive adequate bronchodilator therapy, and the dose of beta-2 agonists may need to be increased. Metoprolol therapy has a lower impact on glucose metabolism or the risk of masking hypoglycemia than non-selective beta-blockers. In rare cases, pre-existing moderate atrioventricular conduction abnormalities may worsen (possibly leading to atrioventricular block). Beta-blocker therapy may interfere with the treatment of allergic reactions, and conventional doses of epinephrine do not always yield the desired effect. Patients with pheochromocytoma who are taking metoprolol succinate should consider concomitant use of an alpha-blocker. Limited controlled clinical trial data exist on the efficacy and safety of tadalafil in patients with severe, symptomatic, stable heart failure (NYHA IV heart function). Therefore, treatment of such patients should be initiated only by experienced and well-trained physicians. Clinical studies in heart failure typically exclude patients with symptomatic heart failure who present with acute myocardial infarction and unstable angina. Therefore, data on the efficacy and safety of tadalafil in the treatment of patients with concurrent acute myocardial infarction and heart failure are lacking. This drug is contraindicated in patients with unstable, decompensated heart failure. Abrupt withdrawal of beta-blockers is dangerous, particularly in high-risk patients, and may worsen chronic heart failure and increase the risk of myocardial infarction and sudden death. Therefore, tadalafil should be withdrawn gradually, over at least two weeks, with the dose reduced by half each time until the dose is reduced to half a 23.75 mg tablet. The last dose should be given at least four days before discontinuation. If symptoms develop, a slower withdrawal is recommended. If tadalafil is to be discontinued before surgery, it must be discontinued at least 48 hours in advance, unless there are specific circumstances, such as thyrotoxicosis or pheochromocytoma. Use with caution in athletes.

[Drug Interactions]
Cardiogenic shock. Sick sinus syndrome. Second and third degree atrioventricular block. Patients with unstable, decompensated heart failure (pulmonary edema, hypoperfusion, or hypotension), patients receiving continuous or intermittent inotropic therapy with beta-agonists. Symptomatic bradycardia or hypotension. This product should not be used in patients with suspected acute myocardial infarction with a heart rate <45 beats/min, a P-Q interval >0.24 seconds, or a systolic blood pressure <100 mmHg. Patients with heart failure indications whose supine systolic blood pressure is consistently below 100 mmHg should have their suitability for this product reassessed before starting treatment. Patients with severe peripheral vascular disease who are at risk of gangrene. Hypersensitivity to any component of this product or other beta-blockers.

[Pediatric Use]
Experience with this product in children is limited.

[Elderly Use]
No dose adjustment is required.

[Use During Pregnancy and Lactation]
Pregnant women: Beta-blockers can cause bradycardia in the fetus or newborn. Therefore, these risks should be considered when using beta-blockers during the last trimester of pregnancy and around the time of delivery. Lactating women: Metoprolol is excreted into breast milk, but therapeutic doses are unlikely to endanger the infant.

[Specifications]
95mg x 7 tablets

[Dosage and Administration]
Oral, once daily, preferably in the morning. The tablets may be broken but not chewed or crushed. They should be taken with at least half a cup of liquid. Concomitant consumption of food does not affect its bioavailability. Dosage should be individualized to avoid bradycardia. The following are effective dosing guidelines: Hypertension: 47.5-95 mg once daily. Patients who do not respond to 95 mg may be treated with other antihypertensive medications, preferably diuretics and dihydropyridine calcium channel blockers, or the dose may be increased. Angina: 95-190 mg once daily. Nitrates may be used or the dose increased as needed. In patients with stable heart failure, treatment with angiotensin-converting enzyme inhibitors, diuretics, and possibly digitalis is recommended. Patients with stable chronic heart failure should not have experienced acute heart failure in at least the past six weeks and should have had their basic treatment unchanged for at least the past two weeks. Treating heart failure with beta-blockers can sometimes cause a temporary worsening of symptoms. In some cases, treatment can be continued or the dosage reduced, while in others, discontinuation of treatment may be necessary. For patients with severe heart failure (NYHA IV), the decision to initiate treatment with metoprolol succinate extended-release tablets should be made only by physicians specifically trained in the treatment of heart failure. Dosage for patients with stable heart failure in class II: The recommended starting dose is 23.75 mg once daily within the first two weeks of treatment. After two weeks, the dose can be increased to 47.5 mg once daily. Thereafter, the dose can be doubled every two weeks. The target dose for long-term treatment is 190 mg once daily. Dosage for patients with stable heart failure class III-IV: The recommended starting dose is 11.875 mg (half a 23.75 mg tablet) once daily. Dosage should be individualized, and patients should be closely observed during dose increases, as heart failure symptoms may worsen in some patients. After one to two weeks, the dose can be increased to 23.75 mg once daily. After an additional two weeks, the dose can be increased to 47.5 mg once daily. For patients who can tolerate higher doses, the dose can be doubled every two weeks to a maximum of 190 mg once daily. Patients with hypotension and/or bradycardia may need to reduce the dose of concomitant medications or the dose of this drug. Initial hypotension does not necessarily mean that the patient will not be able to tolerate this drug in long-term treatment, but the dose should not be increased until the patient's condition has stabilized. Other precautions include the need for increased renal function monitoring. Renal impairment: Renal function has no significant effect on clearance, so no dose adjustment is required in patients with renal impairment. Hepatic Impairment: The dose of metoprolol succinate for patients with cirrhosis is generally the same as for patients with normal liver function. Dose reduction should only be considered in patients with very severe liver impairment (e.g., patients undergoing bypass surgery).

[Adverse Reactions]
Adverse reactions occur in approximately 10% of patients and are generally dose-related. Common: General side effects: fatigue, headache, dizziness (>1/100 patients). Circulatory: Cool extremities, bradycardia. Gastrointestinal: Abdominal pain, nausea, vomiting, diarrhea, and constipation. Uncommon: General side effects: chest pain, weight gain. Circulatory: Temporary worsening of heart failure. Central nervous system: Sleep disturbances, paresthesia. Respiratory: Dyspnea, bronchial asthma, or bronchospasm in patients with asthma symptoms. Rare: General side effects: Hyperhidrosis, alopecia, taste changes, reversible sexual dysfunction (<1/1000). Hematological: Thrombocytopenia. Circulatory: Prolonged atrioventricular conduction time, arrhythmia, edema, syncope. Central nervous system: Nightmares, depression, memory impairment, confusion, nervousness, anxiety, hallucinations. Skin: Allergic skin reaction, exacerbation of psoriasis, photosensitivity. Liver: Elevated aminotransferases. Eyes: Visual impairment. Ears: Tinnitus. Rare cases of arthralgia, hepatitis, painful muscle cramps, dry mouth, conjunctivitis-like symptoms, rhinitis, impaired concentration, and gangrene in patients with concomitant vascular disease have been reported.

[Contraindications]
Cardiogenic shock. Sick sinus syndrome. Second- and third-degree atrioventricular block. Patients with unstable, decompensated heart failure (pulmonary edema, hypoperfusion, or hypotension), patients receiving continuous or intermittent inotropic therapy with beta-agonists. Symptomatic bradycardia or hypotension. This drug should not be administered to patients with suspected acute myocardial infarction whose heart rate is <45 beats/min, P-Q interval >0.24 seconds, or systolic blood pressure <100 mmHg. Patients with heart failure indications whose supine systolic blood pressure is consistently below 100 mmHg should have their suitability for this drug reassessed before initiating treatment. Patients with severe peripheral vascular disease who are at risk of gangrene. Patients with hypersensitivity to any component of this drug or other beta-blockers.

[Overdose]
Toxicity: Metoprolol 7.5g has caused fatal poisoning in adults. A 5-year-old child who accidentally ingested 100mg remained asymptomatic after gastric lavage. A dose of 450 mg causes moderate poisoning in a 12-year-old child, while 1.4 g causes moderate poisoning in an adult, 2.5 g causes severe poisoning, and 7.5 g causes extremely severe poisoning. Symptoms of poisoning: Cardiovascular symptoms are the most prominent, but in some cases, especially in children and young patients, central nervous system symptoms and respiratory depression may be the main manifestations. The main symptoms of poisoning include bradycardia, first- to third-degree atrioventricular block, cardiac arrest, hypotension, poor peripheral perfusion, cardiac insufficiency, cardiogenic shock, respiratory depression, and asphyxia. Other symptoms include fatigue, confusion, loss of consciousness, fine tremors, cramps, sweating, paresthesias, bronchospasm, nausea, vomiting, possible esophageal spasm, hypoglycemia (especially in children) or hyperglycemia, hyperkalemia, kidney effects, and transient myasthenic syndrome. Treatment: For patients with a clear diagnosis, gastric lavage and active pneumococcal contraceptive therapy should be administered. Patients should be treated with a 1.25-0.5 mg dose of acetaminophen (10-20 μg/kg for children). If indicated, endotracheal intubation and respiratory support should be performed. Appropriate volume replacement therapy and glucose infusion should be administered, and electrocardiogram (ECG) monitoring should be performed. Atropine 1.0-2.0 mg intravenously, repeated as needed (primarily to control vagal symptoms). For patients with myocardial depression, dobutamine or dopamine and 10-20 ml of calcium glucopyranoate (9 mg/ml) can be administered via infusion. Another alternative is glucagon 50–150 μg/kg administered intravenously over 1 minute, followed by an intravenous drip, or amrinone. Adding epinephrine is effective in some patients. Patients with widened QRS complexes and arrhythmias can receive an infusion of sodium chloride or sodium bicarbonate. A pacemaker may be required. Patients with cardiac arrest may require resuscitation efforts lasting several hours. Terbutaline (injection or inhalation) can be used to treat bronchospasm. In addition, symptomatic treatment is administered.

[Pharmacology and Toxicology]
Metoprolol is a selective β-1 blocker. Its effect on cardiac β-1 receptors is lower than that on peripheral vascular and bronchial β-2 receptors. The selectivity of metoprolol succinate is dose-dependent. Because the peak plasma concentration of the extended-release tablet is significantly lower than that of the standard tablet at the same dose, this dosage form exhibits relatively higher β-1 receptor selectivity. Metoprolol has no β-receptor agonist activity and has little membrane activation. Beta-blockers have negative inotropic and chronotropic effects. Metoprolol therapy can attenuate the effects of catecholamines associated with physical and psychological stress, reducing heart rate, cardiac output, and blood pressure. Under stressful conditions, adrenal secretion of adrenaline increases, and metoprolol does not interfere with physiological vasodilation. At therapeutic doses, metoprolol has a weaker contraction effect on bronchial smooth muscle than non-selective beta-blockers, a property that allows its combination with beta-2 agonists for the treatment of patients with bronchial asthma or other significant obstructive lung disease. Metoprolol has less effect on insulin release and glucose metabolism than non-selective beta-blockers, making it suitable for use in patients with diabetes. Compared with non-selective beta-blockers, metoprolol has a lesser effect on the cardiovascular effects of hypoglycemia, such as tachycardia, and allows for a faster return of blood sugar to normal levels. In patients with hypertension, metoprolol succinate significantly lowers blood pressure in the upright, supine, and exercise positions, with effects lasting for over 24 hours. An increase in peripheral vascular resistance may be observed at the beginning of metoprolol treatment. However, the reduction in blood pressure achieved with long-term treatment may be due to a decrease in peripheral vascular resistance while maintaining cardiac output. Metoprolol reduces the risk of cardiovascular death in male patients with moderate to severe hypertension. Metoprolol does not cause electrolyte disturbances. Effects on chronic heart failure: In a study (MERIT-HF) involving 3,991 patients with heart failure and NYHA class II-IV and reduced ejection fraction (≤0.40), metoprolol succinate increased survival and reduced hospitalizations. Long-term treatment improved overall symptoms (New York Heart Association class and Global Assessment of Treatment score). Furthermore, metoprolol succinate increases ejection fraction and reduces left ventricular end-systolic and end-diastolic volumes. In patients with tachyarrhythmias, metoprolol blocks the effects of increased sympathetic nerve activity, slowing the heart rate. This occurs primarily by reducing pacemaker cell automaticity and prolonging supraventricular conduction time. In patients after myocardial infarction, metoprolol can reduce the risk of subsequent myocardial infarction and the risk of cardiac death, particularly sudden death, after myocardial infarction.

[Pharmacokinetics]
This product consists of microencapsulated particles of metoprolol succinate; each particle is a separate reservoir unit. Each particle is coated with a polymer film to control the drug release rate. The tablet rapidly disintegrates upon contact with liquid, dispersing the particles over the vast surface area of the gastrointestinal tract. Drug release is unaffected by the pH of the surrounding fluid and remains nearly constant for approximately 20 hours. This dosage form maintains a stable plasma concentration with an effect exceeding 24 hours. Following oral administration, this product is completely absorbed throughout the gastrointestinal tract, including the colon. The bioavailability of this product is 30% to 40%. Metoprolol is metabolized in the liver, and three major metabolites have been identified, none of which have clinically significant beta-blocking activity. Approximately 5% of metoprolol is excreted unchanged by the kidneys; the remainder is metabolized.