carvedilol
Coreg

Available forms
Available by prescription only
Tablets: 3.125 mg, 6.25 mg, 12.5 mg, 25 mg

Indications and dosages
 Hypertension. Adults: Dosage individualized. Initially, 6.25 mg P.O. b.i.d. with food; obtain standing systolic pressure 1 hour after first dose. If tolerated, continue dosage for 7 to 14 days. Can increase to 12.5 mg P.O. b.i.d., repeating monitoring protocol as above. Maximum dosage is 25 mg P.O. b.i.d. as tolerated.
 Mild to severe heart failure. Adults: Dosage individualized and adjusted carefully. Stabilize dosing of cardiac glycosides, diuretics, and ACE inhibitors before starting therapy. Initially, 3.125 mg P.O. b.i.d. with food for 2 weeks; if tolerated, possibly increased to 6.25 mg P.O. b.i.d. for 2 weeks. Dose can be doubled q 2 weeks to highest tolerated level. At start of new dose, observe patient for 1 hour for dizziness or light-headedness. If patient weighs less than 187 lb (85 kg), maximum dosage is 25 mg P.O. b.i.d.; if patient weighs more than 187 lb, maximum dosage is 50 mg P.O. b.i.d.

Pharmacodynamics
Antihypertensive action: Mechanism not established. Beta blockade reduces cardiac output and tachycardia. Alpha blockade is demonstrated by the attenuated pressor effects of phenylephrine, vasodilation, and decreased peripheral vascular resistance.
Heart failure: Not fully established. Drug decreases systemic blood pressure, pulmonary artery pressure, right atrial pressure, systemic vascular resistance, and heart rate while increasing stroke volume index.

Pharmacokinetics
Absorption: Rapidly and extensively metabolized after oral use, with absolute bioavailability of 25% to 35% because of significant first-pass metabolism.
Distribution: Plasma levels are proportional to oral dose. Absorption is slowed by food, as evidenced by a delay in reaching peak plasma levels, with no significant difference in extent of bioavailability.
Metabolism: Extensively metabolized, primarily by aromatic ring oxidation and glucuronidation. The oxidative metabolites are further metabolized by conjugation via glucuronidation and sulfation. Demethylation and hydroxylation at the phenol ring produce three active metabolites with beta-blocking activity.
Excretion: Metabolites are mainly excreted via bile into the feces. Less than 2% of dose is excreted unchanged in urine.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and those with New York Heart Association (NYHA) class IV decompensated cardiac failure who need I.V. inotropic therapy, bronchial asthma or related bronchospastic conditions, second- or third-degree AV block, sick sinus syndrome (unless a permanent pacemaker is in place), cardiogenic shock, or severe bradycardia. Drug isn’t recommended for patients with hepatic impairment.
  Use cautiously in hypertensive patients with left ventricular failure, perioperative patients who receive anesthetics that depress myocardial function (such as ether, cyclopropane, trichloroethylene), diabetic patients receiving insulin or oral antidiabetics, or patients subject to spontaneous hypoglycemia. Also use cautiously in patients with thyroid disease (may mask hyperthyroidism and drug withdrawal may precipitate thyroid storm or an exacerbation of hyperthyroidism), pheochromocytoma, Prinzmetal’s variant angina, or peripheral vascular disease (may precipitate or aggravate symptoms of arterial insufficiency).

Interactions
Drug-drug. Calcium channel blockers: May cause isolated conduction disturbances. Monitor ECG and blood pressure.
Catecholamine-depleting drugs, such as MAO inhibitors, reserpine: May cause severe bradycardia or hypotension. Monitor patient closely.
Cimetidine: Increases bioavailability of carvedilol. Monitor vital signs closely.
Clonidine: May potentiate blood pressure- lowering and heart rate-lowering effects. Monitor patient carefully.
Digoxin: Increases digoxin level (by about 15%). Evaluate digoxin levels.
Insulin, oral antidiabetics: May enhance hypoglycemic effects. Check blood glucose level.
Rifampin: Decreases carvedilol levels (by 70%). Monitor vital signs.
Drug-food. Any food: Delays absorption but not extent of bioavailability. Tell patient to take drug with food to minimize orthostatic effects.

Adverse reactions
CNS: malaise, dizziness,fatigue, headache, hypesthesia, insomnia, pain, paresthesia, somnolence, vertigo, fever, syncope.
CV: aggravated angina pectoris, AV block, bradycardia, chest pain, fluid overload, hypertension, hypotension, orthostatic hypertension, hypovolemia, sudden death, peripheral edema, edema.
EENT: abnormal vision, pharyngitis, rhinitis, sinusitis.
GI: abdominal pain, diarrhea, melena, nausea, periodontitis, vomiting.
GU: abnormal renal function, albuminuria, glycosuria, hematuria, impotence, urinary tract infection.
Hematologic: purpura, thrombocytopenia.
Metabolic: dehydration, gout, hypercholesterolemia, hyperglycemia, hypertriglyceridemia, hypervolemia, hyperuricemia, hypoglycemia, hyponatremia, weight gain, increased nonprotein nitrogen.
Musculoskeletal: arthralgia, back pain, myalgia.
Respiratory: bronchitis, dyspnea, upper respiratory tract infection.
Other: allergy, viral infection.

Effects on lab test results
• May increase BUN, ALT, AST, alkaline phosphatase, cholesterol, glucose, triglyceride, and uric acid levels. May decrease blood glucose, sodium, and nonprotein nitrogen levels.
• May decrease platelet count, PT, and INR.

Overdose and treatment
Overdose may cause severe hypotension, bradycardia, cardiac insufficiency, cardiogenic shock, and cardiac arrest. Respiratory effects, bronchospasm, vomiting, lapses of consciousness, and generalized seizures also may occur.
 Place patient in supine position. Gastric lavage or pharmacologically induced emesis may be effective shortly after ingestion. May use atropine 2 mg I.V. for bradycardia; glucagon 5 to 10 mg I.V. rapidly over 30 seconds, followed by continuous infusion at 5 mg/hour to support CV function; and sympathomimetics (dobutamine, isoprenaline, adrenaline) at doses based on body weight and effect. If peripheral vasodilation dominates, administer epinephrine or norepinephrine, if necessary, and continuously monitor circulatory conditions. For therapy-resistant bradycardia, perform pacemaker therapy. For bronchospasm, give beta-sympathomimetics by aerosol or I.V. or aminophylline I.V. If seizures occur, slow I.V. injection of diazepam or clonazepam may be effective. If severe toxicity and symptoms of shock occur, continue treatment with antidotes for a sufficient period consistent with the drug’s 7- to 10-hour half-life.

Special considerations
• Discontinue drug gradually over 1 to 2 weeks. Decrease dosage if heart rate is less than 55 beats/ minute.
• Patient taking beta blocker with a history of severe anaphylaxis to several allergens may be more reactive to repeated challenge, whether accidental, diagnostic, or therapeutic. Patient may be unresponsive to epinephrine doses usually used to treat allergic reactions.
• Mild hepatocellular injury may occur during therapy. At first sign of hepatic dysfunction, perform tests for hepatic injury or jaundice; if present, discontinue drug.
• Heart failure patients need monitoring for worsened condition, renal dysfunction, or fluid retention; diuretics may need to be increased. Monitor diabetic patient for worsening of hyperglycemia.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. Use cautiously in breast-feeding women.
Pediatric patients
• Safety of drug in patients younger than age 18 hasn’t been established.
Geriatric patients
• Monitor plasma levels carefully; drug levels are about 50% higher in elderly patients than in younger patients.
• There seems to be no significant difference in adverse effects between older and younger patients, although dizziness may be more common in elderly patients.

Patient education
• Tell patient not to interrupt or stop drug without medical approval.
• Advise heart failure patient to report weight gain or shortness of breath.
• Inform patient that he may feel dizzy when he stands up. If he does, tell him to sit or lie down. Fainting is rare.
• Caution patient against performing hazardous tasks at the start of therapy. Tell him to report dizziness or fatigue; he may need a dosage adjustment.
• Advise diabetic patient to report changes in serum glucose level promptly.
• Inform patient who wears contact lenses that he may have decreased tearing.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use