Great Eastern Drug


Zuellig Pharma
Full Prescribing Info
Labetalol HCl.
Excipients/Inactive Ingredients: Dextrose anhydrous, edetate disodium, methyl paraben, propyl paraben, citric acid monohydrate, sodium hydroxide, and water for injection.
Pharmacotherapeutic Group: Labetalol hydrochloride is an alpha and beta blocking agent. ATC Code: C07AG01.
Pharmacology: Pharmacodynamics:
Mechanism of Actions: Labetalol hydrochloride combines both selective, competitive alpha 1-adrenergic blocking and non-selective, competitive beta-adrenergic blocking activity in a single substance.
Labetalol hydrochloride contributes to a decrease in blood pressure in hypertensive patients. It produces dose-related (at usual doses) falls in blood pressure without reflex tachycardia and without significant reduction in resting heart rate, presumably through a mixture of its alpha-blocking effects and beta-blocking effects. Labetalol hydrochloride effectively reduces blood pressure in the standing or supine position, but because of the drug's alpha 1-receptor blocking activity; labetalol hydrochloride-induced decreases in blood pressure are greater in the standing than in the supine position, and orthostatic hypotension can occur. In general, it does not affect renal function in mild to severe hypertensive patients.
Pharmacokinetics: Distribution: Labetalol hydrochloride has been shown to cross the placental barrier in humans. Labetalol hydrochloride is approximately 50% protein bound. Neither hemodialysis nor peritoneal dialysis removes a significant amount of labetalol hydrochloride from the general circulation (<1% of a dose).
Metabolism and Excretion: Following intravenous infusion, the elimination half-life is about 5.5 hours and the total body clearance is approximately 33 mL/min/kg. In patients with decreased hepatic or renal function, the elimination half-life of labetalol hydrochloride is not altered. The metabolism of labetalol hydrochloride is mainly through conjugation to glucuronide metabolites. These metabolites are present in plasma and are excreted in the urine and, via the bile, into the feces. Approximately 55% to 66% of a dose appears in the urine as conjugates or unchanged labetalol hydrochloride within the first 24 hours of dosing.
Labetalol hydrochloride injection is indicated for control of blood pressure in severe hypertension, including severe hypertension of pregnancy, when rapid control of blood pressure is essential.
Dosage/Direction for Use
Adults: Repeated intravenous injection: Initial dosage: Labetalol hydrochloride injection should be given in a dose of 20 mg labetalol hydrochloride (which corresponds to 0.25 mg/kg for an 80 kg patient) by slow intravenous injection over at 2 minute period.
Maintenance dosage: Additional injections of 40 or 80 mg can be given at 10 minute intervals until a desired supine blood pressure is achieved or a total of 300 mg of labetalol hydrochloride has been injected. The maximum effect usually occurs within 5 minutes of each injection.
Slow continuous infusion: 500-200 mg; A total dose of up to 300 mg may be required in some patients at a rate of 2 mg/min. The rate of infusion of a diluted solution may be adjusted according the blood pressure response at the discretion of health care provider.
Avexa is intended for intravenous use.
Overdosage with labetalol hydrochloride injection causes excessive hypotension that is posture sensitive, and sometimes, excessive bradycardia. Patients should be placed supine and their legs raised if necessary to improve the blood supply to the brain. If overdosage with labetalol hydrochloride follows oral ingestion, gastric lavage maybe useful for removal of the drug shortly after ingestion.
The following additional measures should be employed if necessary: Excessive bradycardia: Administer atropine or epinephrine.
Cardiac failure: Administer a digitalis glycoside and a diuretic. Dopamine or dobutamine may also be useful.
Hypotension: Administer vasopressors, e.g. norepinephrine. There is pharmacological evidence that norepinephrine may be the drug of choice.
Bronchospasm: Administer epinephrine and/or an aerosolized beta2-agonist.
Seizures: Administer diazepam.
In severe beta-blocker overdose resulting in hypotension and/or bradycardia, glucagons has been shown to be effective when administered in large doses (5 to 10 mg rapidly over 30 seconds, followed by continuous infusion of 5 mg/hr that can be reduced as the patient improve.
The acute lethal dose of labetalol hydrochloride in humans is not known. The oral LD50 of labetalol hydrochloride is approximately 0.6, greater than 2, and greater than 1 g/kg in mice, rats, and dogs, respectively. The IV LD50 in these species is about 50-60 mg/kg.
Labetalol hydrochloride injection is contraindicated in bronchial asthma, overt cardiac failure, greater than first degree heart block, cardiogenic shock, severe bradycardia (<45-50 bpm), 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 cardio-selectivity, should not be used in patients with a history of obstructive airway disease, including asthma.
When peripheral vasoconstriction suggests low cardiac output, the use of labetalol hydrochloride injection control hypertensive episodes following acute myocardial infarction is contraindicated.
Special Precautions
Hypersensitivity reactions: While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge either accidental diagnostic, or therapeutic. Such patients may be unresponsive to the usual dose of epinephrine used to treat allergic reaction.
Hepatic effect: Severe hepatocellular injury, confirmed by rechallenge in at least one case, occurs rarely with labetalol hydrochloride 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 hydrochloride, including two deaths. Dilevalol hydrochloride is one of the four isomers of labetalol hydrochloride. Thus, for patients taking labetalol hydrochloride, periodic determination of suitable hepatic laboratory tests would be appropriate. Laboratory testing should 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 hydrochloride should be stopped and not restarted.
Cardiac failure/Ischemic Heart Disease: 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 hydrochloride can be used with caution in patients with a history of heart failure who are well compensated (e.g., those controlled with cardiac glycosides and/or diuretics). Congestive heart failure has been observed in patients receiving labetalol hydrochloride. Labetalol hydrochloride does not abolish the inotropic action of digitalis on heart muscle. Although angina pectoris has not been reported upon labetalol hydrochloride discontinuation, exacerbation of angina pectoris and precipitation of myocardial infarction have occurred following abrupt cessation of therapy with some beta-adrenergic blocking agents in patients with coronary artery disease.
Diabetes Mellitus and Hypoglycemia: Labetalol hydrochloride should be used with caution in patients with poorly controlled diabetes mellitus. Beta-blockers can prolong or enhance hypoglycemia by interfering with glycogenolysis. Beta-adrenergic blockade can occasionally cause hyperglycemia. This is thought to be due to blockade of beta-2 receptors on pancreatic islet cells, which would inhibit insulin secretion. Thus, blood glucose levels should be monitored closely if a beta-blocker is used in a patient with diabetes mellitus; it may therefore be necessary to adjust the dose of antidiabetic drugs.
Major surgery: The 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. Several deaths have occurred when labetalol hydrochloride injection was used during surgery (including when used in cases to control bleeding).
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.
Impaired hepatic function: May be diminished metabolism of labetalol hydrochloride injection.
Following coronary artery bypass surgery: In one uncontrolled study, patients with low cardiac indices and elevated systemic vascular resistance following intravenous labetalol hydrochloride experienced significant declines in cardiac output with little change in systemic vascular resistance. One of these patients developed hypotension following labetalol hydrochloride treatment. Therefore, use of labetalol hydrochloride should be avoided in such patients.
High dose labetalol hydrochloride: Administration of up to 3 g/d as an infusion for up to 2-3 days has been anecdotaly reported; several patients have experience hypotension or bradycardia.
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 hydrochloride injection. Therefore, the patient's ability to tolerate an upright position should be established before permitting any ambulation.
Information for patients: Patients should always be kept in a supine position during the period of intravenous drug administration. A substantial fall in blood pressure on standing should be expected in these patients. Raising the patient into the upright position within 3 h of i.v. labetalol hydrochloride injection administration should be avoided since excessive postural hypotension may occur. The patient's ability to tolerate an upright position must be established before permitting any ambulation, such as using toilet facilities.
Effects on ability to drive and use machines: There are no studies on the effect of this medicine on the ability to drive. When driving vehicles or operating machines it should be taken into account that occasionally dizziness or fatigue may occur.
Use in Children: Safety and efficacy in pediatric patients have not been established.
Use in Elderly: Because some geriatric individuals eliminate labetalol hydrochloride more slowly than younger adults, satisfactory blood pressure control may be achieved with lower maintenance doses than those required by younger patients.
Use In Pregnancy & Lactation
Pregnancy category C.
Although no teratogenic effects have been demonstrated in animals, labetalol hydrochloride should only be used during the first trimester of pregnancy if the potential benefit outweighs the potential risk.
Labetalol hydrochloride crosses the placental barrier and the possibility of the consequences of alpha-and beta-adrenoceptor blockade in the fetus and neonate should be borne in mind. Perinatal and neonatal distress (bradycardia, hypotension, respiratory depression, hypoglycemia, hypothermia) has been rarely reported. Sometimes these symptoms have developed a day or two after birth. Response to supportive measures (e.g. intravenous fluids and glucose) is usually prompt but with severe preeclampsia. This may be related to diminish liver metabolism in premature babies.
Beta-blockers reduce placental perfusion, which may result in intrauterine fetal death, immature and premature deliveries. There is an increased risk of cardiac and pulmonary complications in the neonate in the postnatal period. Intrauterine and neonatal deaths have been reported with labetalol hydrochloride but other drugs (e.g. vasodilators, respiratory depressants) and the effects of preeclampsia, intrauterine growth retardation and prematurity were implicated. Such clinical experience warns against unduly prolonging high dose labetalol hydrochloride and delaying delivery and against coadministration of hydralazine.
Labetalol hydrochloride is excreted in breast milk. Breastfeeding is therefore not recommended.
Adverse Reactions
The following also were reported with labetalol hydrochloride injection.
Hypersensitivity reactions: Reported include rash, pruritus, urticaria, angioedema, dyspnea and anaphylactoid reactions.
The following also were reported with labetalol hydrochloride with the incidence per 100 patients.
Cardiovascular system: Ventricular arrhythmia in 1.
CNS: Dizziness, tingling of the scalp/skin in 7, vertigo and hypesthesia (numbness) 1 each.
Gastrointestinal system: Nausea in 13, vomiting in 4, dyspepsia and taste distortion, 1 each.
Metabolic disorders: Transient increases in blood urea nitrogen and serum creatinine levels occur in 8 of 100 patients; these were associated with drops in blood pressure, generally in patients with prior renal insufficiency.
Psychiatric disorders: Somnolence/yawning in 3.
Respiratory system: Wheezing in 1.
Skin: Pruritus in 1.
Drug Interactions
Other antihypertensive agents: Since labetalol hydrochloride may be administered to patients already being treated with other medications, including other antihypertensive agents, careful monitoring of these patients is necessary to detect and treat promptly any undesired effect from concomitant administration.
Beta-agonist bronchodilators: Drugs possessing beta-blocking properties can blunt the bronchodilator effect of beta-receptor agonist drugs in patients with bronchospasm; therefore, doses greater than the normal anti-asthmatic dose of beta-agonist bronchodilator drugs may be required.
Cimetidine: Cimetidine has been shown to increase the bioavailability of labetalol hydrochloride administered orally. Special care should be used in establishing the dose required for blood pressure control in such patients.
Halothane: Synergism has been shown between halothane anesthesia and intravenously administered labetalol hydrochloride.
Nitroglycerin: Labetalol hydrochloride blunts the reflex tachycardia produced by nitroglycerin without preventing its hypotensive effect. If labetalol hydrochloride is used with nitroglycerin in patients with angina pectoris additional antihypertensive effects may occur.
Calcium channel blockers: Care should be taken if labetalol hydrochloride is used concomitantly with calcium antagonists of the verapamil type. Labetalol hydrochloride when administer with alkaline drugs, such as furosemide, and then a white precipitate has been noted. So avoid coadministration.
Caution For Usage
Preparation for administration: Labetalol hydrochloride injection is prepared for continuous intravenous infusion by diluting the contents with commonly used intravenous fluids.
The contents of either two 20 mL vials (40 mL), or one 40 mL vial, are added to 160 mL of a commonly used intravenous fluid, such that the resultant 200 mL of solution contains 200 mg of labetalol hydrochloride, 1 mg/mL.
The diluted solution should be administered at a rate of 2 mL/min to deliver 2 mg/min.
Alternatively, the contents of either two 20 mL vials (40 mL), or one 40 mL vial, of labetalol hydrochloride are added to 250 mL of a commonly used intravenous fluid. The resultant solution will contain 200 mg of labetalol hydrochloride, approximately 2 mg/3 mL to deliver approximately 2 mg/min.
Note: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Blood pressure monitoring: Immediately before the injection and at 5 and 10 minutes after injection, supine blood pressure should be measured to evaluate response.
The blood pressure should be monitored during and after completion of the infusion or intravenous injections. Rapid or excessive falls in either systolic or diastolic blood pressure during intravenous treatment should be avoided. In patients with excessive systolic hypertension, the decrease in systolic pressure should be used as an indicator of effectiveness in addition to response of the diastolic pressure.
Compatibility with commonly used intravenous fluids: Labetalol hydrochloride injection was tested for compatibility with commonly used intravenous fluids at final concentrations of 1.25 to 3.75 mg of labetalol hydrochloride per mL of the mixture. Labetalol hydrochloride was found to be compatible with and stable (for 24 hours refrigerated or at room temperature) in mixture with the following solutions: Ringer's injection, Lactated ringer's injection, 5% dextrose and ringer's injection, 5% Lactated ringer's and 5% Dextrose injection, 5% Dextrose injection, 0.9% Sodium chloride injection, 5% Dextrose and 0.2% Sodium chloride injection, 2.5% Dextrose and 0.45% Sodium chloride injection, 5% Dextrose and 0.9% Sodium chloride injection, 5% Dextrose and 0.33% Sodium chloride injection.
Incompatibilities: Labetalol hydrochloride incompatible with 5% sodium bicarbonate injection. Labetalol hydrochloride solutions containing 1.25-3.75 mg/mL in 5% sodium bicarbonate have a pH of 7.6-8 and from a white precipitate, probably the free bases within 6 hours after admixture. A white precipitate also has been observed following concomitant infusion of other alkaline drugs (e.g., furosemide) and labetalol hydrochloride injection; therefore, labetalol hydrochloride should not be given in the same infusion line with other alkaline solutions.
Store at temperature not exceeding 30°C. Protect from light.
MIMS Class
ATC Classification
C07AG01 - labetalol ; Belongs to the class of alpha and beta blocking agents. Used in the treatment of cardiovascular diseases.
Inj (vial) 5 mg/mL (clear, colorless to light yellow) x 20 mL x 1's.
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