GREENISLAND Carvedilol Tablets For Hypertension 12.5mg*24

[Drug Name]
Generic Name: Carvedilol Tablets
Trade Name: Ludao Carvedilol Tablets 12.5mg*24 Tablets
Pinyin Full Code: LvDao KaWeiDiLuoPian 12.5mg*24 Tablets

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

[Appearance]
This product is white or off-white tablets.

[Indications/Main Functions]
For the treatment of mild to moderate hypertension, either alone or in combination with other antihypertensive drugs (especially thiazide diuretics).

[Precautions]
1. Liver Damage: Carvedilol is used to treat rare mild hepatocellular damage. Laboratory testing is essential at the onset of symptoms of liver dysfunction (such as pruritus, dark urine, persistent loss of appetite, jaundice, right upper abdominal tenderness, or unexplained "flu-like" symptoms). If laboratory tests confirm liver damage or jaundice, the drug must be discontinued immediately and should not be reused. 2. Peripheral Vascular Disease: Beta-blockers may induce or exacerbate symptoms of insufficient arterial blood flow in patients with peripheral vascular disease. Caution is required in such patients. 3. Anesthesia and Major Surgery: If carvedilol is used periodically and long-term, extra caution is required when using cardiodepressant anesthetics such as ether, trimethoprim, and trichloroethylene. 4. Diabetes and Hypoglycemia: Beta-blockers may mask the symptoms of hypoglycemia, especially tachycardia. Non-selective beta-blockers may enhance insulin-induced hypoglycemia and delay the recovery of blood glucose levels. Caution is required when using carvedilol in patients prone to spontaneous hypoglycemia or in diabetic patients receiving insulin or oral hypoglycemic agents. 5. Symptoms of Hyperthyroidism Toxicity: Beta-blockers may mask the symptoms of hyperthyroidism, such as tachycardia. Abrupt discontinuation of beta-blockers may exacerbate symptoms of hyperthyroidism or induce thyroid storm. 6. Because carvedilol has beta-blocking activity, it should not be discontinued abruptly, especially in patients with ischemic heart disease. The drug must be discontinued gradually over 1 to 2 weeks. 7. Carvedilol can cause bradycardia in clinical trials; when the pulse is <55 beats/min, the dose must be reduced. 8. The risk of hypotension, orthostatic hypotension, and syncope is highest within the first 30 days of taking the drug. To reduce the occurrence of these events, the initial treatment dose for patients with heart failure is 3.125 mg twice daily; for patients with hypertension, it is 6.25 mg twice daily. The dose should be increased slowly and taken with food. During the initial treatment period, patients must be careful to avoid situations such as driving or dangerous maneuvers. 9. Worsening of renal function in patients with heart failure is rare, especially in those with hypotension (systolic blood pressure <100 mmHg), ischemic heart disease and diffuse vascular disease, and/or underlying renal insufficiency. Renal function returns to baseline levels after discontinuation of the drug. It is recommended to monitor renal function when increasing the dose in such patients. If renal function worsens, the drug should be discontinued or reduced. 10. During the escalation phase of carvedilol, worsening cardiac dysfunction or fluid retention may occur, necessitating increased diuretics. The carvedilol dose should not be increased until clinical stability is achieved. Occasionally, carvedilol dose reduction or temporary discontinuation may be necessary. 11. Patients with pheochromocytoma should receive an alpha-blocker before using a beta-blocker. Although carvedilol has both beta- and alpha-blocking activity, there is no clinical experience with its use in such patients. Therefore, caution should be exercised when using carvedilol in patients with suspected pheochromocytoma. 12. Non-selective beta-blockers may induce chest pain in patients with variant angina. Although carvedilol's alpha-blocking activity may prevent the onset of angina, there is no clinical experience with its use in such patients. Therefore, caution should be exercised when using carvedilol in patients with suspected variant angina. 13. Risk of allergic reactions: Patients with a history of severe allergic reactions to many allergens may experience more severe reactions to repeated use. Such patients may not respond to conventional doses of epinephrine used for allergy treatment. 14. Non-allergic bronchospasm (such as chronic bronchitis and emphysema). Patients with bronchospastic diseases generally should not use beta-blockers. Carvedilol may be used with caution in patients who do not respond to or cannot tolerate other antihypertensive medications, using the lowest effective dose to minimize inhibition of endogenous or exogenous beta-agonists. 15. Patient Information: ① Do not abruptly discontinue medication without a physician's consent. ② Patients with congestive heart failure should consult a physician if they experience symptoms of worsening heart function, such as weight gain or increased dyspnea. ③ Blood pressure may drop while standing, leading to dizziness and, rarely, fainting. In these cases, sit or lie down. ④ If dizziness or fainting occurs, avoid driving or hazardous work. ⑤ If dizziness or fainting occurs and the dose needs to be adjusted, consult a physician. ⑥ Take with food. ⑦ Patients with diabetes should report any changes in blood sugar levels to their physician. ⑧ Contact lens wearers may experience tearing. 16. Athletes should use with caution.

[Drug Interactions]
1. Patients with NYHA Class IV decompensated heart failure requiring intravenous inotropic therapy; 2. Bronchospasm (two cases of death in patients with persistent asthma after taking a single dose of carvedilol) or related bronchospasm; 3. Second- or third-degree atrioventricular block; 4. Sick sinus syndrome; 5. Cardiogenic shock; 6. Severe bradycardia; 7. Patients with clinically severe hepatic insufficiency; 8. Contraindicated in patients with hypersensitivity to this product; 9. Diabetic ketoacidosis or metabolic acidosis.

[Pediatric Use]
Safety and efficacy in patients <18 years of age are unknown.

[Elderly Use]
Efficacy and adverse event rates do not differ between elderly and younger patients with heart failure or hypertension.

[Pregnancy and Lactation Use]
Human studies are insufficient. Carvedilol should be used in pregnant women only if the benefits to the fetus outweigh the risks. It is unknown whether it is excreted in human breast milk. Many other beta-blockers are excreted into breast milk and can cause potentially serious adverse reactions, such as bradycardia. Therefore, considering the importance of the drug to the mother, breastfeeding women should discontinue the drug or cease breastfeeding.

[Specifications]
12.5mg x 24 tablets

[Dosage and Administration]
Due to significant individual variability, medication should be taken according to a physician's instructions. The recommended starting dose is 5mg (1/4 tablet) twice daily. After two days, it can be increased to 10mg (0.5 tablet) twice daily. If efficacy is still unsatisfactory after two weeks, it can be increased to 20mg (1 tablet) twice daily. The maximum daily dose should not exceed 40mg (2 tablets).

[Adverse Reactions]
1. Hypertension: Incidence ≥ 1%, regardless of causality: fatigue, bradycardia, orthostatic hypotension, postural edema, lower extremity edema, dizziness, insomnia, somnolence, abdominal pain, diarrhea, thrombocytopenia, hyperlipidemia, back pain, viral infection, rhinitis, pharyngitis, dyspnea, urinary tract infection. Incidence > 0.1% to < 1%: limb ischemia, tachycardia, hypokinesia, bilirubinuria, increased transaminases, substernal pain, edema, anxiety, sleep disturbances, worsening depression, inattention, abnormal thinking, emotional lability, asthma, decreased male libido, pruritus, erythema, maculopapular rash, photosensitivity, tinnitus, frequent urination, dry mouth, hyperhidrosis, hypokalemia, diabetes, hyperlipidemia, anemia, leukopenia. Incidence ≤ 0.1%, but significant: third-degree atrioventricular block, bundle branch block, myocardial ischemia, cerebrovascular disorder, convulsions, migraine, neuralgia, alopecia, exfoliative dermatitis, amnesia, gastrointestinal bleeding, bronchial spasm, pulmonary edema, hearing loss, respiratory alkalosis, increased blood urea nitrogen, decreased high-density lipoprotein, pancytopenia. 2. Cardiac insufficiency: Incidence > 2%, irrelevant to causality: hyperhidrosis, fatigue, chest pain, pain, edema, fever, lower extremity edema, bradycardia, hypotension, syncope, atrioventricular block, worsening of angina, dizziness, headache, diarrhea, nausea, abdominal pain, vomiting, thrombocytopenia, weight gain, gout, increased blood urea nitrogen, hyperlipidemia, dehydration, hypervolemia, back pain, arthralgia, myalgia, upper respiratory tract infection, infection, sinusitis, tracheitis, pharyngitis, urinary tract infection, hematuria, abnormal vision. Incidence >1%, <2%: Hypersensitivity, sudden death, malaise, hypovolemia, orthostatic hypotension, decreased sensation, dizziness, melena, periodontitis, elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hyperuricemia, hypoglycemia, hyponatremia, increased alkaline phosphatase (ALP), positive urine glucose, purpura, lethargy, abnormal renal function, and albuminuria. Rare reports of aplastic anemia have occurred only with concomitant use of other medications associated with this event.

[Contraindications]
1. Patients with NYHA class IV decompensated heart failure requiring intravenous inotropic therapy; 2. Bronchospasm (two reports of death in patients with persistent asthma after taking a single dose of carvedilol) or related bronchospastic states; 3. Second- or third-degree atrioventricular block; 4. Sick sinus syndrome; 5. Cardiogenic shock; 6. Severe bradycardia; 7. Patients with clinically severe hepatic insufficiency. 8. This product is contraindicated in patients with a hypersensitivity reaction. 9. Diabetic ketoacidosis and metabolic acidosis.

[Overdose]
Overdose may cause severe hypotension, bradycardia, cardiac insufficiency, cardiogenic shock, and cardiac arrest. Respiratory problems, bronchial spasm, vomiting, loss of consciousness, and convulsions may also occur. The patient should be placed in a supine position and, if necessary, intensive care should be provided. Gastric lavage and emetics may be used. The following medications may be used: 1. Severe bradycardia: Atropine 2 mg intravenously. 2. Cardiovascular support: Glucagon 5-10 mg IV every 30 seconds, followed by 5 mg/hour IV drip. Prompt cardiovascular support should be provided, including cardiopulmonary monitoring, lower extremity elevation, and monitoring of circulating blood volume and urine output. Sympathomimetic drugs (such as dopamine, isoproterenol, and epinephrine) should be used based on weight and efficacy. 3. If peripheral vasodilation is significant, isoproterenol or epinephrine may be necessary with continuous circulatory monitoring. For bradycardia refractory to drug therapy, a pacemaker should be implanted. For bronchospasm, beta-sympathomimetics (aerosol or intravenous) or intravenous aminophylline should be administered. For convulsions, diazepam or clonazepam should be administered slowly intravenously. 4. In the event of severe drug overdose leading to shock, overdose-relief medication must be continued for 7–10 half-lives of carvedilol.

[Pharmacology and Toxicology]
Within the therapeutic dose range, carvedilol exhibits both α1 and nonselective β receptor blocking effects and lacks intrinsic sympathomimetic activity. It blocks postsynaptic α1 receptors, thereby dilating blood vessels and reducing peripheral vascular resistance. It also blocks β receptors, inhibiting renin secretion and disrupting the renin-angiotensin-aldosterone system, resulting in a hypotensive effect. Carvedilol rapidly lowers blood pressure and maintains its antihypertensive effect for a long time. It has no effect on left ventricular ejection fraction, cardiac function, renal function, renal perfusion, peripheral blood flow, plasma electrolytes, or lipid levels. It does not affect heart rate or slightly slows it, and rarely causes water and sodium retention.

[Pharmacokinetics]
Carvedilol is readily absorbed after oral administration, with an absolute bioavailability (F) of approximately 25% to 35%. It exhibits a significant first-pass effect and an elimination half-life (t½b) of approximately 7 to 10 hours. Taking it with food slows its absorption, but does not significantly affect its bioavailability and may reduce the risk of orthostatic hypotension. Carvedilol is a basic, lipophilic compound with a plasma protein binding rate greater than 98%. Its steady-state volume of distribution is approximately 1.5 L, and its plasma clearance is 500 to 700 ml/min. Carvedilol is completely metabolized, with its metabolites excreted in bile and then in feces, with less than 2% excreted unchanged in the urine. Pharmacokinetic measurements were performed on eight healthy subjects after a single 30 mg dose of carvedilol. The peak plasma concentration (Cmax) was 89.89 ng/mL, the elimination half-life (t½b) was 2.01 hours, and the area under the curve (AUC) was 233.1 (ng·h)/mL. Oral absorption of this product is rapid and complete; food may slow absorption and delay peak bioavailability. Due to significant first-pass metabolism, the absolute bioavailability is 25% to 35%. Plasma protein binding is approximately 98%. Maximum serum concentration is reached in approximately 1 hour. The apparent volume of distribution is stable, approximately 115 L. The terminal elimination T½ is 7 to 10 hours. Following oral administration, this product undergoes stereoselective first-pass metabolism. In healthy subjects, the plasma level of the dextrorotatory carvedilol is 2 to 3 times that of the levorotatory carvedilol. The terminal elimination T½ is 5 to 9 hours for the dextrorotatory carvedilol, compared to 7 to 11 hours for the levorotatory carvedilol. The drug is extensively metabolized in the liver, primarily by CYP2D6 and CYP2C9, with others including CYP3A4, 2C19, 1A2, and 2E1. Demethylation and hydroxylation of the phenyl ring produce three metabolites with beta-blocker activity, but weak vasodilator activity. Plasma concentrations are approximately one-tenth that of carvedilol, and pharmacokinetics are similar to those of the parent drug. Less than 2% of carvedilol is excreted unchanged in the urine, with a plasma clearance of 500–700 ml/min. Metabolites are primarily excreted into the feces via bile. Steady-state plasma concentrations in patients with cardiac insufficiency increase proportionally with dose, with increased mean AUC and Cmax, and a terminal elimination T1/2 similar to that in healthy subjects. Plasma concentrations of carvedilol are increased in patients with hepatic and renal impairment. Plasma levels of carvedilol in the elderly are approximately 50% higher than in younger individuals.