Carvedilol	(KAR-ve-dil-ole)
Trade Name(s):	Coreg   ·Tablets 3.125 mg   ·Tablets 6.25 mg   ·Tablets 12.5 mg   ·Tablets 25 mg   Coreg CR   ·Capsules, extended-release 10 mg   ·Capsules, extended-release 20 mg   ·Capsules, extended-release 40 mg   ·Capsules, extended-release 80 mg Apo-Carvedilol PMS-Carvedilol RAN-Carvedilol ratio-Carvedilol Indicates Canadian Trade Name.
Class:	Alpha-adrenergic blocking agent Beta-adrenergic blocking agent
Action:	Blocks alpha-1 receptors and nonselective beta-receptors to decrease BP. Absorption: Rapidly and extensively absorbed. Bioavailability is approximately 25% to 35% because of first-pass metabolism. Food decreases the rate of absorption. Instruct patients to take with food.
	Distribution: More than 98% protein bound, primarily to albumin. Lipophilic, with a Vd of about 115 L. Plasma Cl is 500 to 700 mL/min.
	Metabolism: Undergoes first-pass metabolism. Metabolized by aromatic ring oxidation and glucuronidation; 3 active metabolites are formed, 1 of which is about 13 times more potent than carvedilol. CYP-450 enzymes are involved in carvedilol metabolism.
	Excretion: The t ½ is 7 to 10 h. Less than 2% is excreted unchanged in urine. Metabolites are excreted via the bile into feces.
	Special Populations: Renal Function Impairment - Plasma concentrations may be higher (40% to 50% in those with moderate to severe renal function impairment). Hepatic Function Impairment - Cirrhotic liver disease patients have a 4- to 7-fold increase in concentrations. Use in patients with hepatic function impairment is not recommended. Elderly - Plasma levels are about 50% higher in elderly patients.
	CHF CHF - AUC and C max are increased.
Indications:	Management of essential hypertension; treatment of mild to severe heart failure of ischemic or cardiomyopathic origin; reduction of CV mortality in clinically stable patients who have survived the acute phase of MI and have a left ventricular ejection fraction of 40% or less.
Indications:	Unlabeled use(s): Angina pectoris.
Contraindications:	Decompensated cardiac failure requiring use of IV 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; severe bradycardia; hepatic function impairment; hypersensitivity to the drug.
Interactions:
	Alcohol May affect the modified-release properties of the capsules.
	Antidiabetic agents (insulin and oral agents) Blood glucose-lowering effect may be enhanced.
	Calcium channel blockers (eg, diltiazem) Conduction disturbances may occur and BP may be altered.
	Catecholamine-depleting agents (eg, reserpine) Monitor for hypotension or severe bradycardia.
	Clonidine Heart rate- and BP-lowering effects may be potentiated.
	Cyclosporine, digoxin Plasma levels may be elevated by carvedilol, increasing the therapeutic and adverse reactions.
	Inhibitors of CYP2D6 (eg, fluoxetine, paroxetine, propafenone, quinidine), poor metabolizers of debrisoquine Expected to increase carvedilol blood levels.
	Rifampin May reduce carvedilol plasma levels, decreasing the pharmacologic effect.
	Salicylates (eg, aspirin) Increased risk of hypertension due to inhibition of prostaglandin biosynthesis by salicylates.
	SSRIs (eg, citalopram, fluoxetine) Increased risk of excessive beta blockade (bradycardia) due to increased beta-blocker serum levels resulting from inhibition of beta-blocker metabolism (CYP2D6).
Lab Test Interferences:	None well documented.
Adverse Reactions:
	cardiovascular: Hypotension (14%); bradycardia (10%); syncope (8%); angina pectoris (6%); aggravated angina pectoris, AV block, cerebrovascular accident, fluid overload, hypertension, palpitation, postural hypotension (1% to 3%).
	cns: Dizziness (32%); fatigue (24%); asthenia (11%); headache (8%); lung edema (for treatment of LVD following MI) (more than 3%); depression, hypesthesia, insomnia, malaise, paresthesia, somnolence, vertigo (1% to 3%).
	dermatologic: Purpura (1% to 3%).
	eent: Abnormal vision (5%); blurred vision, pharyngitis (1% to 3%).
	gi: Diarrhea (12%); nausea (9%); vomiting (6%); GI pain, melena, periodontitis (1% to 3%).
	gu: Albuminuria, hematuria, impotence, renal insufficiency, UTI (1% to 3%); urinary incontinence (postmarketing).
	hematologic: Anemia (for treatment of LVD following MI) (more than 3%); prothrombin decreased, thrombocytopenia (1% to 3%); aplastic anemia, leukopenia (postmarketing).
	hepatic: ALT and AST increased (1% to 3%).
	metabolic: Hyperglycemia, weight increase (12%); peripheral edema (7%); BUN and nonprotein nitrogen increase, edema generalized (6%); edema dependent, hypercholesterolemia (4%); creatinine increased, diabetes mellitus, gamma-glutamyl transpeptidase increased, glycosuria, hyperkalemia, hypertriglyceridemia, hyperuricemia, hypervolemia, hypoglycemia, hyponatremia, increased alkaline phosphatase, leg edema, weight loss (1% to 3%).
	musculoskeletal: Arthralgia (6%); back pain, muscle cramps (1% to 3%).
	respiratory: Upper respiratory tract infection (18%); increased cough (8%); bronchitis, sinusitis (5%); rales (4%); dyspnea (for treatment of LVD following MI) (more than 3%); interstitial pneumonitis (postmarketing).
	miscellaneous: Pain (9%); allergy, arthritis, fever, flu syndrome, hypotonia, hypovolemia, infection, peripheral vascular disorder, viral infection (1% to 3%).
Precautions:
	Monitoring:
	Blood sugar Monitor blood sugar in diabetic patients when drug is initiated, adjusted, or discontinued.
	BP Monitor and record BP and pulse in hypertensive patients. Should hypotension occur, hold medication.
	Orthostatic hypotension Monitor CHF patients for orthostatic hypotension (eg, dizziness, light-headedness, change in BP) for 1 h after first dose and at initiation of each dose increase.
	Weight/Respiratory status Monitor weight and respiratory status in CHF patients.
	Pregnancy: Category C .
	Lactation: Undetermined.
	Children: Safety and efficacy not established.
	Elderly: Carvedilol plasma levels average 50% higher in elderly compared with young subjects; however, there were no notable differences in efficacy or adverse reactions.
	Renal function impairment: May result in deterioration of renal function.
	Special risk patients: Use with caution in patients with CHF, pheochromocytoma, or Prinzmetal variant angina.
	Anaphylactic reaction Patients receiving a beta-blocking agent and who have a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reactions.
	Anesthesia and major surgery If carvedilol is continued perioperatively, use with caution with anesthetic agents that depress myocardial function (eg, ether).
	Bronchial asthma Death in patients with status asthmaticus has occurred.
	Diabetes and hypoglycemia May mask symptoms of hypoglycemia, particularly tachycardia; may potentiate insulin-induced hypoglycemia and delay recovery of serum glucose levels.
	Discontinuation Because carvedilol has beta-blocking activity, do not discontinue abruptly. Severe exacerbation of angina and occurrence of MI and ventricular arrhythmias have been reported. Discontinue over 1 or 2 weeks.
	Hepatic toxicity Mild hepatocellular injury may occur. Perform laboratory testing at first signs or symptoms of liver dysfunction. If there is laboratory evidence of liver injury or jaundice, stop carvedilol therapy and do not restart.
	Nonallergic bronchospasm In general, patients with bronchospastic disease should not receive beta-blocker therapy. In patients who do not respond to, or cannot tolerate, other antihypertensive agents, carvedilol may be used with caution and in the smallest effective dose so that inhibition of endogenous or exogenous beta-agonists is minimized.
	Peripheral vascular disease Because symptoms of arterial insufficiency may be aggravated or precipitated in patients with peripheral vascular disease, use with caution in such patients.
	Thyrotoxicosis May mask signs of hyperthyroidism, such as tachycardia; abrupt withdrawal may exacerbate symptoms of hyperthyroidism and precipitate thyroid storm.
Overdosage:	Signs & symptoms Bradycardia, bronchospasms, cardiac arrest, cardiac insufficiency, cardiogenic shock, generalized seizures, lapses of consciousness, respiratory problems, severe hypotension, vomiting.
Patient/Family Education:	Advise patient that medication is started at a low dose and gradually increased as needed and tolerated. Instruct patient not to interrupt therapy or discontinue drug abruptly. Remind patient to take each dose with food to reduce risk of orthostatic hypotension. Caution patient to avoid sudden position changes to prevent orthostatic hypotension. Instruct patient to lie or sit down if experiencing dizziness or light-headedness when standing. Instruct patient in BP and pulse measurement skills. Instruct CHF patient to measure and record BP, pulse, weight, and symptoms daily and to report abnormal measurements. Take record to each follow-up office visit. Emphasize importance of a healthy lifestyle (eg, weight control, regular exercise, smoking cessation, moderate intake of alcohol and salt) to hypertensive patient. Advise patient to separate the administration of this medication from alcohol consumption, including ethanol-containing prescription and OTC medicines, by at least 2 h. Instruct patient not to crush or chew this medication and to swallow whole. Alternatively, capsules may be opened and the beads sprinkled over a spoonful of applesauce. Instruct diabetic patient to monitor blood glucose more frequently when dose is changed or drug is stopped. Patient should inform health care provider of any changes in readings. Advise patients who wear contact lenses that drug may cause decreased tearing and dry eyes. Instruct patient to report any of these symptoms to health care provider: bradycardia, dark urine, fainting or persistent dizziness when arising from a sitting or lying position, fatigue, increasing shortness of breath, persistent anorexia, pruritus, right upper quadrant tenderness, swelling of feet or ankles, unexplained flu-like symptoms, or weight gain. Caution patient that drug may cause dizziness or fainting and to avoid driving or performing other hazardous tasks until tolerance is determined. Remind CHF patients that they should be seen by health care provider before each dose change and to keep appointments.