Brand name: Carvedilol Hexal 6.25 mg
Active ingredient (generic name): Carvedilol
Manufacturer: Hexal
Importer: Behestan Darou
Pharmacotherapeutic group: Alpha and beta blocking agents
Pharmaceutical form: 6.25 mg Tablet
Pharmacodynamic:
Carvedilol is a nonselective β-adrenergic blocking agent with α1-blocking activity. It is a vasodilating non-selective beta-blocking agent with antioxidant properties. Vasodilation is predominantly mediated through alpha1 receptor antagonism. Carvedilol reduces the peripheral vascular resistance through vasodilation and suppresses the renin-angiotensin-aldosterone system through beta-blockade.
Pharmacokinetic:
Carvedilol is highly lipophilic; approximately 98% to 99% is bound to plasma proteins. The distribution volume is approximately 2 l/kg and increased in patients with liver cirrhosis. The first pass effect after oral administration is approximately 60 - 75%; enterohepatic circulation of the parent substance has been shown in animals.
The average elimination half-life ranges from 6 to 10 hours. Plasma clearance is approximately 590ml/min. Elimination is mainly biliary. The primary route of excretion is via the faeces. A minor portion is eliminated via the kidneys in the form of various metabolites.
Therapeutic indication:
Carvedilol is indicated for the treatment of Symptomatic chronic heart failure (CHF), Hypertension and Angina.
Dosage and administration:
The recommended dose for the initiation of therapy is 3.125mg twice a day for two weeks. If this dose is tolerated, the dosage should be increased subsequently, at intervals of not less than two weeks, to 6.25mg twice daily, followed by 12.5mg twice daily and thereafter 25mg twice daily. Dosing should be increased to the highest level tolerated by the patient.
The recommended maximum daily dose is 25mg given twice daily for all patients with severe CHF and for patients with mild to moderate CHF weighing less than 85kg (187lbs). In patients with mild or moderate CHF weighing more than 85kg, the recommended maximum dose is 50mg twice daily.
Adverse reaction:
The most common adverse events are Bronchitis, pneumonia, upper respiratory tract infection, urinary tract infection, Anemia Weight increase, hypercholesterolemia, impaired blood glucose control ,Nausea, diarrhea, vomiting, dyspepsia, abdominal pain.
Contraindication:
Chronic congestive heart failure: In congestive heart failure patients, worsening cardiac failure or fluid retention may occur during up-titration of Carvedilol.
Carvedilol should be used with caution in combination with digitalis glycosides since both drugsmay slow A-V conduction (see section 4.5).
Renal function in congestive heart failure: Reversible deterioration of renal function has been observed with Carvedilol therapy in chronic heart failure patients with low blood pressure (systolic BP < 100mmHg), ischaemic heart disease and diffuse vascular disease, and/or underlying renal insufficiency. In CHF patients with these risk factors, renal function should be monitored during up-titration of Carvedilol and the drug discontinued or dosage reduced if worsening of renal failure occurs.
Bronchospatic reactions: In patients with a tendency to bronchospastic reactions, respiratory distress can occur as a result of a possible increase in airway resistance.
Diabetes: Care should be taken in the administration of Carvedilol to patients with diabetes mellitus as the early signs of acute hypoglycaemia may be masked or attenuated.
Peripheral vascular disease: Carvedilol should be used with caution in patients with peripheral vascular disease since beta-blockers can precipitate or aggravate symptoms of arterial insufficiency. However as Carvedilol also have alpha-blocking properties this effect is largely counterbalanced.
Thyrotoxicosis: Carvedilol, as with other agents with beta-blocking activity, may mask the symptoms of thyrotoxicosis.
Bradycardia: Carvedilol may induce bradycardia. If the patient's pulse rate decreases to less than 55 beats per minute, the dosage of Carvedilol should be reduced.
Hypersensitivity: Care should be taken in administering Carvedilol to patients with a history of serious hypersensitivity reactions and in those undergoing desensitization therapy as beta-blockers may increase both the sensitivity towards allergens and the seriousness of anaphylactic reactions.
Pharmacokinetic interactions
Digoxin: Digoxin concentrations are increased by about 16% when digoxin and carvedilol are administered concomitantly. Both digoxin and carvedilol slow AV conduction. Increased monitoring of digoxin levels is recommended when initiating, adjusting or discontinuing carvedilol.
Inducers and inhibitors of hepatic metabolism: Rifampicin reduced plasma concentrations of carvedilol by about 70%. Cimetidine increased AUC by about 30% but caused no change in Cmax. Care may be required in those receiving inducers of mixed function oxidases e.g. rifampicin, as serum levels of carvedilol may be reduced or inhibitors of mixed function oxidases e.g. cimetidine, as serum levels may be increased. However based on the relatively small effect of cimetidine on carvedilol drug levels the likelihood of any clinically important interaction is minimal.
Pregnancy and lactation:
There is no adequate clinical experience with Carvedilol in pregnant women.
Animal studies are insufficient with respect to effects on pregnancy; embryonal/foetal development, parturition and postnatal development (see section 5.3). The potential risk for humans is unknown.
Carvedilol should not be used during pregnancy unless the potential benefit outweighs the potential risk.
Beta blockers reduce placental perfusion, which may result in intrauterine foetal death, and immature and premature deliveries. In addition, adverse effects (especially hypoglycaemia and bradycardia) may occur in the foetus and neonate. There may be an increased risk of cardiac and pulmonary complications in the neonate in the postnatal period. Animal studies have not shown substantive evidence of teratogenicity with Carvedilol (see also section 5.3)
Animal studies demonstrated that Carvedilol or its metabolites are excreted in breast milk. It is not known whether Carvedilol is excreted in breast milk. Breast feeding is therefore not recommended during administration of Carvedilol.
Storage temperature: Room temperature (15-25 C).
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