WARNINGS

Hepatic InjurySevere hepatocellular injury, confirmed by rechallenge in at least one case, occurs rarely with therapy with labetalol.

The hep tic injury is usually reversible, but hepatic necrosis and death have been reported.

Injury has occurred after both short- and long-term treatment and may be slowly progressive despite minimal symptomatology.

Similar hepatic events have been reported with a related compound, dilevalol HCl, including two deaths.

Dilevalol HCl is one of the four isomers of labetalol HCl.

Thus, for patients taking labetalol, periodic determination of suitable hepatic laboratory tests would be appropriate.

Laboratory testing should also be done at the very first symptom or sign of liver dysfunction (e.g., pruritus, dark urine, persistent anorexia, jaundice, right upper quadrant tenderness, or unexplained “flu-like” symptoms).

If the patient has jaundice or laboratory evidence of liver injury, labetalol should be stopped and not restarted.

Cardiac FailureSympathetic stimulation is a vital component supporting circulatory function in congestive heart failure.

Beta blockade carries a potential hazard of further depressing myocardial contractility and precipitating more severe failure.

Although beta-blockers should be avoided in overt congestive heart failure, if necessary, labetalol can be used with caution in patients with a history of heart failure who are well-compensated.

Congestive heart failure has been observed in patients receiving labetalol HCl.

Labetalol does not abolish the inotropic action of digitalis on heart muscle.

In Patients Without a History of Cardiac FailureIn patients with latent cardiac insufficiency, continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure.

At the first sign or symptom of impending cardiac failure, patients should be fully digitalized and/or be given a diuretic, and the response observed closely.

If cardiac failure continues, despite adequate digitalization and diuretic, therapy with labetalol should be withdrawn (gradually if possible).

Exacerbation of Ischemic Heart Disease Following Abrupt WithdrawalAngina pectoris has not been reported upon labetalol discontinuation.

However, hypersensitivity to catecholamines has been observed in patients withdrawn from beta-blocker therapy; exacerbation of angina and, in some cases, myocardial infarction have occurred after abrupt discontinuation of such therapy.

When discontinuing chronically administered labetalol, particularly in patients with ischemic heart disease, the dosage should be gradually reduced over a period of 1 to 2 weeks and the patient should be carefully monitored.

If angina markedly worsens or acute coronary insufficiency develops, labetalol administration should be reinstituted promptly, at least temporarily, and other measures appropriate for the management of unstable angina should be taken.

Patients should be warned against interruption or discontinuation of therapy without the physician’s advice.

Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue therapy with labetalol abruptly even in patients treated only for hypertension.

Nonallergic bronchospasm (e.g., chronic bronchitis and emphysema) patients with bronchospastic disease should, in general, not receive beta-blockers.

Labetalol may be used with caution, however, in patients who do not respond to, or cannot tolerate, other antihypertensive agents.

It is prudent, if labetalol is used, to use the smallest effective dose, so that inhibition of endogenous or exogenous beta-agonists is minimized.

PheochromocytomaLabetalol has been shown to be effective in lowering the blood pressure and relieving symptoms in patients with pheochromocytoma.

However, paradoxical hypertensive responses have been reported in a few patients with this tumor; therefore, use caution when administering labetalol to patients with pheochromocytoma.

Diabetes Mellitus and HypoglycemiaBeta-adrenergic blockade may prevent the appearance of premonitory signs and symptoms (e.g., tachycardia) of acute hypoglycemia.

This is especially important with labile diabetics.

Beta-blockade also reduces the release of insulin in response to hyperglycemia; it may therefore be necessary to adjust the dose of antidiabetic drugs.

Major SurgeryThe necessity or desirability of withdrawing beta-blocking therapy prior to major surgery is controversial.

Protracted severe hypotension and difficulty in restarting or maintaining a heartbeat have been reported with beta-blockers.

The effect of labetalol’s alpha-adrenergic activity has not been evaluated in this setting.

A synergism between labetalol and halothane anesthesia has been shown (see PRECAUTIONS-Drug Interactions).