Learn a Drug a Day - Labetalol hydrochloride

Today's drug is labetalol hydrochloride.
What is labetalol hydrochloride indicated for?
INDICATIONS : 

• Labetalol HCl tablets are indicated in the management of hypertension. 
• Labetalol HCl tablets may be used alone or in combination with other antihypertensive agents, especially thiazide and loop diuretics.
• Labetalol HCl injection is indicated for control of blood pressure in severe hypertension.

How does labetalol HCl work?

MECHANISMS OF ACTION : 

• Labetalol competitively inhibits the adrenergic stimulation of β-receptors within the myocardium, bronchial and vascular smooth muscle, and α1-receptors within vascular smooth muscle. 
• It also has some intrinsic β2-agonist and membrane-stabilising activity.

How is labetalol HCl being used?

ROUTE OF ADMINISTRATION : 

• It can be taken orally as tablets.
• It can also be taken intravenously as hypotensive anaesthesia.
• It should be taken with food. (take immediately after meals.)

Is there any contraindication?

CONTRAINDICATIONS : 

• It is contraindicated in bronchial asthma, overt cardiac failure, greater-than-first-degree heart block, cardiogenic shock, severe bradycardia, other conditions associated with severe and prolonged hypotension, and in patients with a history of hypersensitivity to any component of the product.
• Beta-blockers, even those with apparent cardioselectivity, should not be used in patients with a history of obstructive airway disease, including asthma.

Are there any possible side effects?

SIDE EFFECTS : 

(i) Common possible side effects : 

• Cardiovascular System - Ventricular arrhythmia.
• Central and Peripheral Nervous Systems - Dizziness, tingling of the scalp/skin, hypoesthesia (numbness) and vertigo
• Gastrointestinal System - Nausea, vomiting, dyspepsia and taste distortion.
• Metabolic Disorders - Transient increases in blood urea nitrogen and serum creatinine levels, these were associated with drops in blood pressure, generally in patients with prior renal insufficiency.
• Psychiatric Disorders - Somnolence/yawning.
• Respiratory System - Wheezing.
• Skin - Pruritus.

(ii) Rare possible side effects : 

• Cardiovascular System - Hypotension, and rarely, syncope, bradycardia, heart block.
• Liver and Biliary System - Hepatic necrosis, hepatitis, cholestatic jaundice, elevated liver function tests.
• Hypersensitivity - Rare reports of hypersensitivity (e.g., rash, urticaria, pruritus, angioedema, dyspnea) and anaphylactoid reactions.

What precautions are necessary?

PRECAUTIONS :  

(i) Impaired Hepatic Function

• Labetalol HCl should be used with caution in patients with impaired hepatic function since metabolism of the drug may be diminished.

(ii) Hypotension

• Symptomatic postural hypotension (incidence 58%) is likely to occur if patients are tilted or allowed to assume the upright position within 3 hours of receiving labetalol injection. Therefore, the patient's ability to tolerate an upright position should be established before permitting any ambulation.

(iii) Intraoperative Floppy Iris Syndrome (IFIS) 

• has been observed during cataract surgery in some patients treated with alpha-1 blockers (labetalol is an alpha/beta blocker). This variant of small pupil syndrome is characterized by the combination of a flaccid iris that billows in response to intraoperative irrigation currents, progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs, and potential prolapse of the iris toward the phacoemulsification incisions. The patient’s ophthalmologist should be prepared for possible modifications to the surgical technique, such as the utilization of iris hooks, iris dilator rings, or viscoelastic substances. There does not appear to be a benefit of stopping alpha-1 blocker therapy prior to cataract surgery.

(iv) Following Coronary Artery Bypass Surgery

• In one uncontrolled study, patients with low cardiac indices and elevated systemic vascular resistance following intravenous labetalol experienced significant declines in cardiac output with little change in systemic vascular resistance. One of these patients developed hypotension following labetalol treatment. Therefore, use of labetalol should be avoided in such patients.

(v) High-Dose Labetalol

• Administration of up to 3 g/d as an infusion for up to 2 to 3 days has been anecdotally reported; several patients experienced hypotension or bradycardia.

(vi) Jaundice or Hepatic Dysfunction

• Severe hepatocellular injury, confirmed by rechallenge in at least one case, occurs rarely with labetalol therapy. The hepatic 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. 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.

(vii) Cardiac Failure

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

(viii) In Patients without a History of Cardiac Failure

• In patients with latent cardiac insufficiency, continued depression of the myocardium with beta-blocking agents over a period of time can lead, in some cases, 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, labetalol therapy should be withdrawn (gradually if possible).

(ix) Ischemic Heart Disease

• Angina pectoris has not been reported upon labetalol discontinuation. However, following abrupt cessation of therapy with some beta-blocking agents in patients with coronary artery disease, exacerbations of angina pectoris and, in some cases, myocardial infarction have been reported. Therefore, such patients should be cautioned against interruption of therapy without the physician’s advice. Even in the absence of overt angina pectoris, when discontinuation of labetalol is planned, the patient should be carefully observed and should be advised to limit physical activity. 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.

(x) Nonallergic Bronchospasm (e.g., chronic bronchitis and emphysema)

• Patients with bronchospastic disease should, in general, not receive beta-blockers. 
• Since labetalol injection at the usual intravenous therapeutic doses has not been studied in patients with nonallergic bronchospastic disease, it should not be used in such patients.
• Labetalol HCl tablets may be used with caution, however, in patients who do not respond to, or cannot tolerate, other antihypertensive agents. It is prudent, if  labetalol HCl tablets are used, to use the smallest effective dose, so that inhibition of endogenous or exogenous beta-agonists is minimized. 

(xi) Pheochromocytoma

• Labetalol HCl has been shown to be effective in lowering the blood pressure and relieving symptoms in patients with pheochromocytoma; higher than usual doses may be required. However, paradoxical hypertensive responses have been reported in a few patients with this tumor; therefore, use caution when administering labetalol to patients with pheochromocytoma.

(xii) Diabetes Mellitus and Hypoglycemia

• Beta-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.

(xiii) Major Surgery

• Do not routinely withdraw chronic beta blocker therapy prior to surgery. The effect of labetalol’s alpha adrenergic activity has not been evaluated in this setting.
• Several deaths have occurred when labetalol injection was used during surgery (including when used in cases to control bleeding).
• A synergism between labetalol and halothane anesthesia has been shown.

(xiiii) Rapid Decreases of Blood Pressure

• Caution must be observed when reducing severely elevated blood pressure. A number of adverse reactions, including cerebral infarction, optic nerve infarction, angina, and ischemic changes in the electrocardiogram, have been reported with other agents when severely elevated blood pressure was reduced over time courses of several hours to as long as 1 or 2 days. The desired blood pressure lowering should therefore be achieved over as long a period of time as is compatible with the patient's status.

DRUG INTERACTIONS : 

• Increased bioavailability with cimetidine. 
• Decreased bioavailability with glutethimide. 
• Increased incidence of tremors with TCAs(tricycline antidepressants). 
• Additive hypotensive effect with nitroglycerin.
• Increased risk of bradycardia with drugs that slows AV conduction. 
• Synergistic hypotensive effect with halothane.
• More drug interactions --> click here! 

Pregnancy and breastfeeding:  

• There are no adequate and well-controlled studies in pregnant women. Labetalol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
• Small amounts of labetalol (approximately 0.004% of the maternal dose) are excreted in human milk. Caution should be exercised when labetalol HCl is administered to a nursing woman.

1. Labetalol HCl by Prometheus Laboratories Inc.

2. Labetalol HCl by Daily Med.

3. Labetalol HCl by MIMS Malaysia.