Product Overview
[Drug Name]
Generic Name: H Carvedilol Tablets
Trade Name: Jinluo H Carvedilol Tablets 12.5mg*14 Tablets
Pinyin Full Code: JinLuo HKaWeiDiLuoPian 12.5mg*14 Tablets
[Main Ingredients]
Active ingredient: Carvedilol. One tablet contains 3.125mg, 6.25mg, 12.5mg, or 25mg of carvedilol. Tablets are for oral use.
[Properties]
See package insert for details.
[Indications/Main Functions]
1. Essential Hypertension: Carvedilol is indicated for the treatment of essential hypertension, either alone or in combination with other antihypertensive drugs, particularly thiazide diuretics. 2. Treatment of Symptomatic Congestive Heart Failure: Carvedilol is used to treat symptomatic congestive heart failure and can reduce mortality and cardiovascular hospitalization rates, improve the patient's general condition, and slow disease progression. Carvedilol can be used as an add-on to standard therapy and can also be used for patients who are intolerant to ACE inhibitors or who are not receiving digitalis, hydralazine, or nitrates.
[Specifications]
12.5 mg x 14 tablets
[Dosage and Administration]
1. For essential hypertension: Once daily is recommended. Adults: The recommended dose is 12.5 mg once daily for the first two days, followed by 25 mg once daily. If necessary, the dose can be increased after two weeks to the maximum recommended dose of 50 mg once daily or in divided doses. Elderly: An initial dose of 12.5 mg once daily has been shown to achieve satisfactory results in some patients. If the response is insufficient, the dose can be increased to the maximum recommended dose of 50 mg once daily or in divided doses after a delay of at least two weeks. 2. For the treatment of symptomatic congestive heart failure: The dose must be individualized, and close observation is required during dose increases. Patients receiving digoxin, diuretics, or ACE inhibitors must be stabilized on these medications before using carvedilol. The recommended initial dose is 3.125 mg twice daily for two weeks. If well tolerated, the dose can be increased after at least two weeks to 6.25 mg twice daily, then to 12.5 mg twice daily, and finally to 25 mg twice daily. The dose must be increased to the patient's tolerance. For patients weighing less than 85 kg, the maximum recommended dose is 25 mg twice daily; for those weighing more than 85 kg, the maximum recommended dose is 50 mg twice daily. Before each dose increase, the physician should assess the patient for symptoms of worsening heart failure or vasodilation. Transient worsening heart failure or sodium and water retention may require increasing the diuretic dose, sometimes reducing the carvedilol dose, or temporarily discontinuing carvedilol therapy. If carvedilol is discontinued for more than two weeks, reinitiation should start with 3.125 mg twice daily and then increase the dose as recommended above. Symptoms of vasodilation can be initially managed by reducing the diuretic dose. If symptoms persist, the dose of the ACE inhibitor (if used) should be reduced, and then the carvedilol dose should be further reduced if necessary. In these cases, the carvedilol dose should not be increased until the heart failure worsens or the vasodilation symptoms stabilize. 3. Duration of Treatment: Carvedilol treatment is generally required long-term. Treatment should not be discontinued abruptly; the dose must be gradually reduced. This is particularly important for patients with coronary artery disease. 4. Administration: The time of administration is not related to meals, but for patients with congestive heart failure, carvedilol must be taken with meals to slow absorption and potentially reduce the occurrence of orthostatic hypotension.
[Adverse Reactions]
1. Hypertension: Incidence ≥ 1%, regardless of causal relationship: fatigue, bradycardia, orthostatic hypotension, postural edema, lower limb edema, dizziness, insomnia, somnolence, abdominal pain, diarrhea, thrombocytopenia, hyperlipidemia, back pain, viral infection, rhinitis, pharyngitis, dyspnea, urinary tract infection. Incidence > 0.1%, < 1%: limb ischemia, tachycardia, hypokinesia, bilirubinuria, increased transaminases, substernal pain, edema, anxiety, sleep disturbance, worsening depression, inattention, abnormal thinking, emotional lability, asthma, decreased male libido, pruritus, erythema, maculopapular rash, photosensitivity reaction, tinnitus, frequent urination, dry mouth, hyperhidrosis, hypokalemia, diabetes, hyperlipidemia, anemia, leukopenia. Incidence ≤ 0.1%, but important: third-degree atrioventricular block, bundle branch block, myocardial ischemia, cerebrovascular disorder, convulsion, migraine, neuralgia, exfoliative dermatitis alopecia, 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 limb edema, bradycardia, hypotension, syncope, atrioventricular block, worsening 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]
Carvedilol is contraindicated in the following patients: 1. Hypersensitivity to any component of this product. 2. New York Heart Association class IV decompensated heart failure requiring intravenous inotropic therapy. 3. Asthma, chronic obstructive pulmonary disease (COPD) with bronchospasm, and allergic rhinitis. 4. Patients with abnormal liver function. 5. Second- to first-degree atrioventricular block, severe bradycardia (heart rate less than 50 beats/min), sick sinus syndrome (including sinoatrial block). 6. Cardiogenic shock. 7. Severe hypotension (systolic blood pressure less than 85 mmHg). 8. Within 48 hours before surgery.
[Drug Interactions]
1. Like other beta-blockers, carvedilol may enhance the effects of other concomitant antihypertensive drugs (such as alpha-blockers) or cause hypotension.2. When carvedilol is taken orally with diltiazem, some patients may experience cardiac conduction disturbances (rarely with hemodynamic effects). As with other beta-blocking drugs, when carvedilol is used concomitantly with calcium channel blockers or class I antiarrhythmic drugs, such as verapamil and diltiazem, the patient's electrocardiogram (ECG) and blood pressure should be closely monitored, and intravenous coadministration of these drugs is strictly prohibited.3. In hypertensive patients, the concomitant use of carvedilol with digoxin may increase the steady-state trough concentration of digoxin by 16%. Therefore, digoxin plasma concentrations should be monitored closely during the initiation, dose adjustment, and discontinuation of carvedilol.
4. When discontinuing the concomitant use of carvedilol and clonidine, the carvedilol should be discontinued first, and the clonidine dose should be gradually reduced over several days. 5. Carvedilol may enhance the effects of insulin or oral hypoglycemic agents, potentially masking or diminishing the symptoms and signs of hypoglycemia (especially tachycardia). Therefore, regular monitoring of blood glucose levels is recommended. 6. When carvedilol is used in patients receiving mixed-function oxidase inducers such as rifampicin, carvedilol blood concentrations may be reduced. When used in patients receiving mixed-function oxidase inhibitors such as cimetidine, carvedilol blood concentrations may be increased. Therefore, caution should be exercised. 7. When carvedilol is used in patients under anesthesia, the patient should be closely monitored for negative inotropic effects and hypotension caused by synergistic effects of carvedilol and anesthetics. 8. The combined use of carvedilol and cardiac glycosides may prolong atrioventricular conduction time.
[Precautions]
1. Because carvedilol and digitalis can both slow atrioventricular conduction velocity, carvedilol should be used with caution in patients with congestive heart failure whose condition is controlled with digitalis, diuretics, and angiotensin-converting enzyme inhibitors. 2. Because carvedilol may mask or attenuate the early signs and symptoms of acute hypoglycemia, carvedilol should be used with caution in patients with diabetes. Carvedilol may make blood sugar control difficult in patients with congestive heart failure who are also diabetic. Therefore, during the initial treatment phase of this medication, blood sugar should be monitored regularly and the dosage of antidiabetic medication adjusted accordingly. 3. Carvedilol treatment of patients with congestive heart failure (CHF) associated with hypotension (systolic blood pressure less than 100 mmHg), ischemic heart disease, diffuse vascular disease, or renal insufficiency can cause reversible renal dysfunction. When increasing the carvedilol dose in such patients, renal function should be closely monitored. If renal function declines, the carvedilol dose should be reduced or discontinued. 4. In patients with CHF, increasing the carvedilol dose may worsen heart failure and water and sodium retention. In this case, the diuretic dose should be increased and the carvedilol dose should not be increased until these conditions resolve. In rare cases, the carvedilol dose may need to be reduced or temporarily discontinued. These circumstances generally do not affect subsequent increases in the carvedilol dose. 5. Unless the benefits outweigh the risks, carvedilol should only be used in patients with chronic obstructive pulmonary disease who do not require oral or inhaled bronchial antispasmodics. Patients prone to bronchospasm may experience increased airway resistance, leading to respiratory distress. Therefore, the patient's respiratory status should be closely monitored during the initial use of carvedilol and during dose increases. If any evidence of bronchospasm is observed during treatment, the carvedilol dosage should be promptly reduced. 6. Contact lens wearers should be aware that this drug may cause dry eyes. 7. When discontinuing carvedilol treatment, do not stop abruptly. This is especially true for patients with ischemic heart disease. In such patients, the dosage should be gradually reduced and then discontinued over 1-2 weeks. 8. Like other beta-blockers, carvedilol may mask the symptoms of hyperthyroidism. 9. Because beta-blockers may increase the risk of allergic reactions or worsen them, carvedilol should be used with caution in patients with a history of severe allergies or those undergoing desensitization therapy. 10. The risks and benefits of carvedilol should be considered before using it in patients with beta-blocker-associated psoriasis. 11. Before using carvedilol in patients with chromochromocytoma, an alpha-blocker should be used first. Although carvedilol has both alpha- and beta-blocking pharmacological effects, there is no clinical experience with its use in this patient population. Therefore, caution should be exercised in patients with suspected chromochromocytoma. 12. In patients with Prinzmetali's variant angina, the use of nonselective beta-blockers may cause chest pain. Although carvedilol's alpha-blocking effect may prevent the onset of angina, there is currently no clinical experience with its use in this patient population. Therefore, caution should be exercised in patients with suspected Prinzmetali's variant angina. 13. Caution should be exercised in the use of carvedilol in patients with peripheral vascular disease, as beta-blockers may exacerbate arterial insufficiency. 14. Carvedilol may exacerbate the condition of patients with peripheral vascular disorders (such as Raynaud's phenomenon). 15. Caution should be exercised in the use of carvedilol in surgical patients, as carvedilol can synergize with anesthetics, resulting in negative inotropic effects and hypotension. 16. Carvedilol may induce bradycardia. If the heart rate drops below 55 beats/min, the carvedilol dose should be reduced. 17. When carvedilol is used concomitantly with calcium channel blockers such as verapamil and diltiazem, or other medications, the patient's electrocardiogram and blood pressure should be closely monitored. 18. Due to a lack of clinical experience, caution should be exercised in patients with unstable or secondary hypertension. Effects on Drivers and Machine Operators: Carvedilol may reduce alertness (e.g., the ability to drive and operate machinery). This effect varies from person to person and is more pronounced at the start of treatment, during dose changes, and during concomitant alcohol use. 19. Use with caution in athletes.
[Use in Elderly Patients]
This drug is primarily metabolized in the liver. Patients with severe liver impairment may experience persistently elevated blood concentrations. Elderly patients often have impaired liver function. Therefore, elderly patients should be started with a low dose and closely monitored.
[Overdose]
In the event of severe sinus bradycardia caused by an overdose, initially administer atropine sulfate (0.25-1 mg) intravenously. Subsequently, as needed, beta-agonists such as isoproterenol hydrochloride (initial 25 μg slow intravenously) or metaproterenol sulfate (0.5 mg slow intravenously) may be administered. If the dose of the beta-agonist must be increased, care should be taken to avoid excessive hypertension.
[Pharmacology and Toxicology]
Carvedilol is a neurohumoral antagonist with multiple actions, including non-selective beta-blocking, alpha-blocking, and antioxidant properties. It dilates blood vessels by selectively blocking α1-adrenergic receptors. Carvedilol reduces peripheral resistance through vasodilation and inhibits the renin-angiotensin-aldosterone system through beta-blockade. Plasma renin activity is reduced, and fluid retention is rare. Carvedilol lacks the intrinsic sympathomimetic activity of propranolol and exhibits membrane stabilizing properties. Carvedilol is a racemic mixture of two stereoisomers. In animal models, both isomers exhibit α-adrenergic receptor blocking properties. The β-adrenergic receptor blocking effect is non-selective, targeting β1 and β2 adrenergic receptors and is associated with the levorotatory form of carvedilol. Carvedilol exhibits antioxidant properties, inhibiting the effects of oxygen free radicals. The antioxidant properties of carvedilol and its metabolites have been demonstrated through in vitro and in vivo animal studies, in vitro studies using various human cell lines, and clinical studies.
