Carvedilol

Carvedilol tablets are an alpha/beta-adrenergic blocking agent indicated for the treatment of: mild to severe chronic heart failure ( 1.1 ) left ventricular dysfunction following myocardial infarction in clinically stable patients( 1.2 ) hypertension( 1.3 ) 1.1 Heart Failure Carvedilol tablets are indicated for the treatment of mild-to-severe chronic heart failure of ischemic or cardiomyopathic origin, usually in addition to diuretics, ACE inhibitors, and digitalis, to increase survival and, also, to reduce the risk of hospitalization [see Drug Interactions ( 7.4 ), Clinical Studies ( 14.1 )] . …

• Take with food
• Individualize dosage and monitor during up-titration
• Heart failure: Start at 3.125 mg twice daily and increase to 6.25, 12.5, and then 25 mg twice daily over intervals of at least 2 weeks
• Maintain lower doses if higher doses are not tolerated
• Left ventricular dysfunction following myocardial infarction: Start at 6.25 mg twice daily and increase to 12.5 mg then 25 mg twice daily after intervals of 3 to 10 days
• A lower starting dose or slower titration may be used
• Hypertension: Start at 6.25 mg twice daily and increase if needed for blood pressure control to 12.5 mg and then 25 mg twice daily over intervals of 1 to 2 weeks
• Carvedilol should be taken with food to slow the rate of absorption and reduce the incidence of orthostatic effects
• Heart Failure DOSAGE MUST BE INDIVIDUALIZED AND CLOSELY MONITORED BY A PHYSICIAN DURING UP-TITRATION
• Prior to initiation of Carvedilol tablets, it is recommended that fluid retention be minimized
• The recommended starting dose of Carvedilol tablets are 3.125 mg twice daily for 2 weeks
• If tolerated, patients may have their dose increased to 6.25, 12.5, and 25 mg twice daily over successive intervals of at least 2 weeks
• Patients should be maintained on lower doses if higher doses are not tolerated
• A maximum dose of 50 mg twice daily has been administered to patients with mild-to-moderate heart failure weighing over 85 kg (187 lbs). …

Tablets: 3.125 mg, 6.25 mg, 12.5 mg, 25 mg ( 3 ) The white to off-white, round, film-coated tablets are available in the following strengths: 3.125 mg– debossed with Z and 1, 6.25 mg–debossed with ZC40, 12.5 mg–debossed with ZC41 and 25 mg–debossed with ZC42.

• Effectiveness of carvedilol tablets in patients younger than 18 years has not been established
• In a double-blind trial, 161 children (mean age: 6 years; range: 2 months to 17 years; 45% younger than 2 years) with chronic heart failure [NYHA class II-IV, left ventricular ejection fraction less than 40% for children with a systemic left ventricle (LV), and moderate-severe ventricular dysfunction qualitatively by echo for those with a systemic ventricle that was not an LV] who were receiving standard background treatment were randomized to placebo or to 2 dose levels of carvedilol. …

Of the 765 subjects with heart failure randomized to carvedilol in US clinical trials, 31% (235) were aged 65 years or older, and 7.3% (56) were aged 75 years or older. Of the 1,156 subjects randomized to carvedilol in a long-term, placebo-controlled trial in severe heart failure, 47% (547) were aged 65 years or older, and 15% (174) were aged 75 years or older. …

• Advise the patient to read the FDA-approved patient labeling (Patient Information)
• Patients taking carvedilol tablets should be advised of the following: Patients should take carvedilol tablets with food
• Patients should not interrupt or discontinue using carvedilol tablets without a physician's advice
• Patients with heart failure should consult their physician if they experience signs or symptoms of worsening heart failure such as weight gain or increasing shortness of breath
• Patients may experience a drop in blood pressure when standing, resulting in dizziness and, rarely, fainting
• Patients should sit or lie down when these symptoms of lowered blood pressure occur. …

• Bronchial asthma or related bronchospastic conditions
• Second- or third-degree AV block
• Sick sinus syndrome
• Severe bradycardia (unless permanent pacemaker in place)
• Patients in cardiogenic shock or decompensated heart failure requiring the use of IV inotropic therapy
• Severe hepatic impairment. …

CYP P450 2D6 enzyme inhibitors may increase and rifampin may decrease carvedilol levels. ( 7.1 , 7.5 ) Hypotensive agents (e.g., reserpine, MAO inhibitors, clonidine) may increase the risk of hypotension and/or severe bradycardia. ( 7.4 ) Cyclosporine or digoxin levels may increase. ( 7.3 , 7.4 ) Both digitalis glycosides and β-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia. ( 7.4 ) Amiodarone may increase carvedilol levels resulting in further slowing of the heart rate or cardiac conduction. ( 7.6 ) Verapamil- or diltiazem-type calcium channel blockers may affect ECG and/or blood pressure. …

Acute exacerbation of coronary artery disease upon cessation of therapy: Do not abruptly discontinue. ( 5.1 ) Bradycardia, hypotension, worsening heart failure/fluid retention may occur. Reduce the dose as needed. ( 5.2 , 5.3 , 5.4 ) Non-allergic bronchospasm (e.g., chronic bronchitis and emphysema): Avoid β-blockers. ( 4 ) However, if deemed necessary, use with caution and at lowest effective dose. ( 5.5 ) Diabetes: May mask symptoms of hypoglycemia and alter glucose levels; monitor ( 5.6 ) 5.1 Cessation of Therapy Patients with coronary artery disease, who are being treated with carvedilol tablets, should be advised against abrupt discontinuation of therapy. …

Most common adverse events ( 6.1 ): Heart failure and left ventricular dysfunction following myocardial infarction (≥10%): Dizziness, fatigue, hypotension, diarrhea, hyperglycemia, asthenia, bradycardia, weight increase. Hypertension (≥5%): Dizziness. To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc. at 1- 877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. …

8.1 Pregnancy Risk Summary Available data regarding use of carvedilol in pregnant women are insufficient to determine whether there are drug-associated risks of adverse developmental outcomes. There are risks to the mother and fetus associated with poorly controlled hypertension in pregnancy. …

Overdosage may cause severe hypotension, bradycardia, cardiac insufficiency, cardiogenic shock, and cardiac arrest. Respiratory problems, bronchospasms, vomiting, lapses of consciousness, and generalized seizures may also occur. The patient should be placed in a supine position and, where necessary, kept under observation and treated under intensive-care conditions. The following agents may be administered: For excessive bradycardia: Atropine, 2 mg IV. …

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