Caraten

Carvedilol.

Caraten 6.25: each tablet contains carvedilol 6.25 mg.
Caraten 12.5: each tablet contains carvedilol 12.5 mg.
Caraten 25: each tablet contains carvedilol 25 mg.

Pharmacodynamics: Mechanism of Action: Systemic: Carvedilol is a nonselective beta-adrenergic blocking agent with alpha 1-adrenergic blocking activity and no intrinsic sympathomimetic activity. The exact mechanism of the antihypertensive effect produced by beta-adrenergic blockade, may involve suppression of renin production. The beta-adrenergic blocking activity of carvedilol decreases cardiac output, exercise- and /or isoproterenol-induced tachycardia, and reflex orthostatic tachycardia. The alpha 1-adrenergic blocking activity of carvedilol blunts the pressor effect of phenylephrine, causes vasodilation, and reduces peripheral vascular resistance. The effect of alpha1-adrenergic blockade is a reduction in standing blood pressure (more than supine), presenting symptoms of postural hypotension and possibly syncope.
The mechanism by which carvedilol produces a beneficial effect in congestive heart failure is not known, but may be attributable to beta-adrenergic blockade and vasodilation.
Pharmacokinetics: Onset: hypertension, oral: Initial Response 1 hour, Peak Response 4 to 7 hours.
Duration: Single Dose, Hypertension, Oral: 24 hours.
Absorption: Rapid and extensive.
Bioavailability: 25 to 35%; food slows absorption.
Protein Binding: 95% to 98%.
Distribution: Volume of Distribution 115 L.
Metabolism: Hepatic: extensively via P450 2D6 pathway; Active metabolite: 4'-hydroxyphenyl.
Excretion: Fecal/Biliary.
Elimination Half Life: Carvedilol 6 to 10 h.

Hypertension; Angina pectoris; Impaired left ventricular function following myocardial infarction; Heart failure.

Recommended Dose: Hypertension: an initial oral dose is 12.5 mg once daily increased after two days to 25 mg once daily. Alternatively, an initial dose of 6.25 mg is given twice daily, increased after one or two weeks to 12.5 mg twice daily. The dose may be increased further, if necessary, at intervals of at least two weeks to 50 mg once daily or in divided doses (twice daily). A dose of 12.5 mg once daily maybe adequate in elderly patients.
Angina pectoris: an initial dose is 12.5 mg orally twice daily, increased after two days to 25 mg twice daily.
Impaired left ventricular function following myocardial infarction: the initial dose is 6.25 mg orally twice daily; increased after 3 to 10 days, if tolerated, to 12.5 mg twice daily and then to a target dose of 25 mg twice daily. A lower initial dose may be used in symptomatic patients.
Heart failure: the initial dose is 3.125 mg orally twice daily. If tolerated, the dose should be doubled after two weeks to 6.25 mg twice daily and then increased gradually, at intervals of not less than two weeks, to the maximum dose tolerated; this should not exceed 25 mg twice daily in patients with severe heart failure or in those weighing less than 85 kg, or 50 mg twice daily in patients with mild to moderate heart failure weighing more than 85 kg.
If a Dose is Missed: If the patient misses a dose or forgets to use the medicine, use as soon as he/she can. If it is almost time for the next dose, wait until then to use the medicine and skip the missed dose. Do not use extra medicine to make up for a missed dose.
Dose Adjustments: Dosage in Renal Failure: carvedilol are excreted less than 1% and dosing adjustments are not required in patients with renal insufficiency.
Dosage Adjustment During Dialysis: Dosing adjustments are not required in chronic hemodialysis patients.
Dosage in Hepatic Insufficiency: Carvedilol is extensively metabolized in the liver and dose reductions are suggested in patients with hepatic insufficiency. Initiated with approximately 20% of the normal dose in patients with liver cirrhosis.
Dosage in Geriatric Patients: elderly subjects may be more susceptible to the postural hypotensive effects of carvedilol, suggesting that lower doses should be considered initially.
Pediatric Dosing: safety and efficacy in children have not been established.
Mode of Administration: Tablets for oral use. Should be taken with food to minimize the risk of orthostatic hypotension.

Overdose: Little human data. Hypotension, bradycardia and QRS widening have been reported. Hypoglycemia (especially in children and diabetics), decreased mental status and seizures are possible but not yet reported. ADVERSE EFFECTS: Hypotension, orthostatic hypotension, syncope, bradycardia and dizziness can occur.
Treatment: Decontamination: Activated charcoal, gastric lavage.
Hypotensive episode: IV 0.9% NS, dopamine, norepinephrine. If bradycardic administer atropine, glucagon (bolus of 50 to 150 mcg/kg over 1 minute {usually about 10 mg in an adult} then a continuous IV infusion of 1 to 5 mg/hour in D5W).
Hypoglycemia: Intravenous dextrose.
Seizure: Benzodiazepines, barbiturates.
Monitoring of patient: Monitor blood pressure frequently. Institute continuous cardiac monitoring and obtain an ECG. Monitor blood glucose in patients with decreased mental status, children and diabetics.

atrioventricular block, second- or third-degree;
bradycardia, severe (if no pacemaker is present);
bronchial asthma or related bronchospastic condition; status asthmaticus resulting in death has been reported;
cardiogenic shock;
heart failure, decompensated and requiring IV inotropic therapy;
hepatic impairment, severe;
hypersensitivity (eg, Stevens-Johnson syndrome, anaphylactic reaction, angioedema) to carvedilol or any component of the product;
sick sinus syndrome.

Chronic Congestive Heart Failure: In congestive heart failure patients, worsening cardiac failure or fluid retention may occur during up-titration of carvedilol. If such symptoms occur, diuretics should be increased and the carvedilol dose should not be advanced until clinical stability resumes. Occasionally, it may be necessary to lower the carvedilol dose or, in rare cases, temporarily discontinue it. Such episodes do not preclude subsequent successful titration of carvedilol. Carvedilol should be used with caution in combination with digitalis glycosides, as both drugs slow AV conduction.
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<100 mm Hg), ischemic heart disease and diffuse vascular disease, and/or underlying renal insufficiency.
Chronic obstructive pulmonary disease: Carvedilol should be used with caution, in patients with chronic obstructive pulmonary disease (COPD) with a bronchospastic component who are not receiving oral or inhaled medication, and only if the potential benefit outweighs the potential risk.
In patients with a tendency to bronchospasm, respiratory distress can occur as a result of possible increase in airway resistance. Patients should be closely monitored during initiation and up titration of carvedilol and the dose of carvedilol should be reduced if any evidence of bronchospasm is observed during treatment.
Diabetes: Care should be taken in the administration of carvedilol to patients with diabetes mellitus, as the early signs and symptoms of acute hypoglycemia may be masked or attenuated. In chronic heart failure patients with diabetes, the use of carvedilol may be associated with worsening control of blood glucose.
Peripheral vascular disease: Carvedilol should be used with caution in patients with peripheral vascular disease as β-blockers can precipitate or aggravate symptoms of arterial insufficiency.
Raynaud's phenomenon: Carvedilol should be used with caution in patients suffering from peripheral circulatory disorders (e.g. Raynaud's phenomenon) as there may be exacerbation of symptoms.
Thyrotoxicosis: Carvedilol, like other agents with β-blocking properties, may obscure the symptoms of thyrotoxicosis.
Anesthesia and major surgery: Caution should be exercised in patients undergoing general surgery, because of the synergistic negative inotropic effects of carvedilol and anesthetic drugs.
Hypersensitivity: Care should be taken in administering carvedilol to patients with a history of serious hypersensitivity reactions, and in those undergoing desensitization therapy, as β-blockers may increase both the sensitivity towards allergens and the seriousness of anaphylactic reactions.
Psoriasis: Patients with a history of psoriasis associated with β-blocker therapy should take carvedilol only after consideration of the risk - benefit ratio.
Concomitant use of calcium channel blockers: Careful monitoring of ECG and blood pressure is necessary in patients receiving concomitant therapy with calcium channel blockers of the verapramil or diltiazem type or other antiarrhythmic drugs.
Pheochromocytoma: In patients with pheochromocytoma, an α-blocking agent should be initiated prior to the use of any β-blocking agents. Although carvedilol has both α- and β-blocking pharmacological activities, there is no experience with its use in this condition. Caution should therefore be taken in the administration of carvedilol to patients suspected of having pheochromocytoma.
Prinzmetal's variant angina: Agents with non-selective β-blocking activity may provoke chest pain in patients with Prinzmetal's variant angina. There is no clinical experience with carvedilol in these patients although the α-blocking activity of carvedilol may prevent such symptoms. Caution should, however, be taken in the administration of carvedilol to patients suspected of having Prinzmetal's variant angina.
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.
Contact lenses: Wearers of contact lenses should bear in mind the possibility of reduced lacrimation.
Ability to drive and use machines: No studies have been performed on the effects of carvedilol on patients fitness to drive or to operate machinery. Because of individually variable reactions (e.g. dizziness, tiredness), the ability to drive, operate machinery, or work without firm support may be impaired. This applies particularly at the start of treatment, after dose increases, on changing products, and in combination with alcohol.

Pregnancy Category: C.
Studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.
Lactation: Infant risk cannot be ruled out.
Available evidence and/or expert consensus is inconclusive or is inadequate for determining infant risk when used during breastfeeding. Weigh the potential benefits of drug treatment against potential risks before prescribing this drug during breastfeeding.

>10%: CV: Hypotension.
CNS: Dizziness, Fatigue.
Endocrine and metabolic: Hyperglycemia.
GI: Diarrhea, Weight gain.
Neuromuscular & skeletal: Weakness.
1-10%: CV: Bradycardia, syncope, peripheral and generalized edema, angina, dependent edema, AV block, Cerebrovascular accident, hypertension, hyper-/hypovolemia, postural hypotension, palpitation.
CNS: headache, depression, fever, hypoesthesia, hypotonia, insomnia, malaise, somnolence, vertigo.
Endocrine & metabolic: hypercholesterolemia, hypertriglyceridemia, diabetes mellitus, gout, hyperkalemia, hyperuricemia, hypoglycemia, hyponatremia.
GI: nausea, vomiting, abdominal pain, melena, periodontitis, weight loss, impotence.
Hematologic: anemia, prothrombin decreased, purpura, thrombocytopenia.
Hepatic: alkaline phosphate increased, GGT increased, transaminases increased.
Neuromuscular & skeletal: back pain, arthralgia, arthritis, muscle cramps, paresthesia.
Others: blurred vision, BUN increased, nonprotein nitrogen increased, albuminuria, creatinine increased, glycosuria, hematuria, renal insufficiency.

Metabolism/Transport Effects Substrate of CYP1A2 (minor), CYP2C9 (major), CYP2D6 (major), CYP2E (minor), CYP3A4 (minor), P-glycoprotein; lnhibits P-glycoprotein: Avoid Concomitant Use: Avoid concomitant use of Carvedilol with any of the following: Dabigatran Etexilate; Methacholine; Topotecan.
lncreased Effect/Toxicity: Carvedilol may increase the levels/effects of: Alpha-/Beta- Agonist(Direct-Acting); Alpha1-Blockers; Alpha2-Agonists; Amifostine; Antihypertensive; Antipsychotic Agents(phenothiazine); Cardiac Glycosides; Colchicine; Cyclosporin; Dabigatran Etexilate; Digoxin; hypotensive agents; Insulin; Lidocaine systemic and topical; Methacholine; Midodrine; P-Glycoprotein Substrates; Rituximab; Rivaroxaban; Sulfonylureas; Topotecan.
The levels/effects of Carvedilol may be increased by Acetylcholinesterase inhibitors; Aminoquinolines(antimalarial); Amiodarone; Anilidopiperidine Opioids; Phenothiazines; Non-dihydropyridine calcium channel blockers; Cimetidine; CYP2C9 inhibitors (moderate/ strong); CYP2D6 inhibitors (moderate /strong); Darunavir; Diazoxide; Dipyridamole; Disopyramide; Dronedarone; Herbs (Hypotensive properties); MAO Inhibitors; Pentoxifylline; P-Glycoprotein Inhibitors; Phosphodiesterase 5 Inhibitors; Propafenone; Propoxyphene; Prostacyclin Analogues; Quinidine; Reserpine; Selective Serotonin Reuptake Inhibitors.
Decreased Effect: Carvedilol may decrease the level/effects of: Beta2 Agonists; Theophylline Derivatives.
The levels/effects of Carvedilol may be decreased by Barbiturates; Herbs(hypertensive properties); Methylphenidate; NSAIDs; Peginterferon Alfa-2b; P-Glycoprotein inducers; Rifampicin Derivatives; Yohimbine.

Store below 30 °C, protect from light and moisture.

Beta-Blockers

C07AG02 - carvedilol ; Belongs to the class of alpha and beta blocking agents. Used in the treatment of cardiovascular diseases.

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