Pharmaniaga Labetalol HCl

Pharmaniaga Labetalol HCl

labetalol

Manufacturer:

Pharmaniaga LifeScience

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Full Prescribing Info
Contents
Labetalol hydrochloride.
Description
Each 5mL contains Labetalol hydrochloride 25mg.
Preservative Free.
Action
Pharmacology: Pharmacodynamics: Labetalol lowers blood pressure by blocking peripheral arteriolar α-adrenoceptors, thus reducing peripheral resistance, and by concurrent β-blockade, protects the heart from reflex sympathetic drive that would otherwise occur. Cardiac output is not significantly reduced at rest or after moderate exercise. Increases in systolic blood pressure during exercise are reduced but corresponding changes in diastolic pressure are essentially normal. All these effects would be expected to benefit hypertensive patients.
Labetalol does not adversely affect renal function and is particularly suitable for use in hypertensive patients with renal disease.
Pharmacokinetics: The plasma half-life of Labetalol is about four hours. About 50% of Labetalol in the blood is protein bound. Labetalol is metabolised mainly through conjugation to inactive glucuronide metabolites. These are excreted both in the urine and via the bile, into the faeces. Only negligible amounts of Labetalol cross the blood brain barrier in animal studies. Labetalol crosses the placental barrier and secreted in breast milk.
Indications/Uses
Severe hypertension, including severe hypertension of pregnancy, when rapid control of blood pressure is essential.
Anaesthesia when a hypotensive technique is indicated.
Hypertensive episodes following acute myocardial infarction.
Dosage/Direction for Use
Labetalol hydrochloride injection is intended for i.v. use in hospitalised patients. Patients should always receive the drug whilst in the supine or left lateral position. Raising the patient into the upright position within 3 h of i.v. Labetalol hydrochloride administration should be avoided since excessive postural hypotension may occur. It is desirable to monitor the blood pressure and heart rate after injection and during infusion. In most patients, there is a small decrease in the heart rate; severe bradycardia is unusual but may be controlled by injecting atropine 1 to 2 mg intravenously. Respiratory function should be observed particularly in patients with any known impairment.
Once the blood pressure has been adequately reduced by bolus injection or infusion, maintenance therapy with Labetalol hydrochloride tablets should be substituted with a starting dose of 100 mg twice daily. Labetalol hydrochloride injection has been administered to patients with uncontrolled hypertension already receiving other hypotensive agents, including beta-blocking drugs, without adverse effects.
Adults: For Severe Hypertension: Bolus injection: If it is essential to reduce the blood pressure quickly a dose of 50 mg should be given by i.v. injection (over a period of at least 1 min) and, if necessary, repeated at 5 min intervals until a satisfactory response occurs. The total dose should not exceed 200 mg. The maximum effect usually occurs within 5 min and the duration of action is usually about 6 h but may be as long as 18 h.
Intravenous Infusion: A 1 mg/mL solution of Labetalol hydrochloride injection should be used, i.e. the contents of two 20 mL vials or eight 5 mL ampoules (200 mg) diluted to 200 mL with Sodium Chloride and Dextrose Intravenous Infusion.
Severe Hypertension of Pregnancy: Infusion should be started at 20 mg/h, then doubled every 30 min until a satisfactory response is obtained or a dosage of 160 mg/h is reached. Occasionally higher doses may be necessary.
Hypertension Due To Other Causes: Infusion should be started at a rate of 2 mg/min until a satisfactory response is obtained, then stopped. The effective dose is usually 50 to 200 mg but larger doses may be needed, especially in patients with phaeochromocyto­ma. The rate of infusion may be adjusted according to the response at the discretion of the physician.
For Hypotensive Anaesthesia: Induction should be with standard agents (e.g. Sodium thiopentone) and anaesthesia maintained with nitrous oxide and Oxygen with or without Halothane. The recommended starting dose of Labetalol hydrochloride is 10 to 20 mg intravenously depending on the age and condition of the patient. Patients for whom Halothane is contraindicated usually require a higher initial dose of Labetalol hydrochloride (25 to 30 mg). If satisfactory hypotension is not achieved after 5 min, increments of 5 to 10 mg should be given until the desired level of blood pressure is attained.
Halothane and Labetalol hydrochloride act synergistical­ly therefore the Halothane concentration should not exceed 1 to 1.5% as profound falls in blood pressure may be precipitated. Following Labetalol hydrochloride injection the blood pressure can be quickly and easily adjusted by altering the Halothane concentration and/or adjusting table tilt. The mean duration of hypotension following 20 to 25 mg of i.v. Labetalol hydrochloride is 50 min. Hypotension induced by Labetalol hydrochloride injection is readily reversed by Atropine 0.6 mg and discontinuation of Halothane.
Tubocurarine and Pancuronium may be used when assisted or controlled ventilation is required. Intermittent positive pressure ventilation may further increase the hypotension resulting from Labetalol hydrochloride injection and/or Halothane.
For Hypertensive Episodes Following Acute Myocardial Infarction: Infusion should be started at 15 mg/h and gradually increased to a maximum of 120 mg/h depending on the control of blood pressure.
Compatible Solutions: Pharmaniaga Labetalol hydrochloride 25mg/5ml injection is compatible with the following i.v. infusion fluids: 5% Dextrose, 0.18% Sodium Chloride and 4% Dextrose, 0.3% Potassium Chloride and 5% Dextrose, Compound Sodium Lactate.
The solution should be clear, colorless when diluted. Do not use if the solution is discolored or if there is particu­late matter in the solution.
Overdosage
Overdosage with Labetalol hydrochloride 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.
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 pharmacologic 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, glucagon 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/h that can be reduced as the patient improves).
Contraindications
Labetalol hydrochloride injection is contraindicated in second or third degree heart block, cardiogenic shock and other conditions associated with severe and prolonged hypotension or severe bradycardia.
Beta-blockers, even those with apparent cardioselectivity, should not be used in patients with asthma or a history of obstructive airways disease.
Labetalol hydrochloride injection is contraindicated for patients known to have hypersensitivity to the drug.
When peripheral vasoconstriction suggests low cardiac output, the use of Labetalol hydrochloride injection to control hypertensive episodes following acute myocardial infarction is contraindicated.
Special Precautions
There have been rare reports of severe hepatocellular injury with Labetalol therapy. The hepatic injury is usually reversible and has occured after both short and long term treatment. Appropriate laboratory testing should be done at the first sign or symptom of liver dysfunction.
If there is laboratory evidence of liver injury or the patient is jaundiced, Labetalol therapy should be stopped and not restarted.
Labetalol hydrochloride injection should be used with caution in patients with peripheral vascular disease as their symptoms may be exacerbated.
If the patient develops symptomatic bradycardia, then the dosage of Labetalol hydrochloride injection should be reduced.
Given the negative effect of beta-adrenoceptor blocking drugs on atrioventricular conduction time, Labetalol hydrochloride injection should be administered with caution to patients with first-degree atrio-ventricular block.
Special care should be taken with patients who suffer from heart failure or poor left ventricular systolic function. Heart failure should be controlled with appropriate therapy before use of Labetalol.
Labetalol hydrochloride injection need not be discontinued prior to anaesthesia but patients should receive intravenous Atropine prior to induction.
In patients with pheochromocytoma, Labetalol may be administered only after adequate alpha-blockade is achieved.
During anaesthesia Labetalol hydrochloride injection may mask the compensatory physiological responses of sudden haemorrhage (tachycardia and vasoconstriction).
Close attention must therefore be paid to blood loss and the blood volume maintained.
Particular care should be taken when Labetalol is used in patients with hepatic impairment as these patients metabolise Labetalol more slowly than patients without hepatic impairment.
As with other beta-adrenoceptor blocking drugs, Labetalol hydrochloride injection may mask the symptoms of hypoglycemia in diabetic patients and thyrotoxicosis.
Risk of anaphylactic reaction: While taking β-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 doses of epinephrine used to treat allergic reaction.
If patients receiving Labetalol require Adrenaline treatment, a reduced dosage of adrenaline should be used as concomitant administration of Labetalol with Adrenaline may result in bradycardia and hypertension.
There have been reports of skin rashes and/or dry eyes associated with the use of beta-adrenoceptor blocking drugs. The reported incidence is small and in most cases the symptoms have cleared when the treatment was withdrawn. Gradual discontinuance of the drug should be considered if any such reaction is not otherwise explicable.
The occurrence of intraoperative Floppy Iris Syndrome (IFIS, a variation of Small Pupil Syndrome) has been observed during cataract surgery in some patients on , or previously treated with, Tamsulosin. Isolated reports have also been received with other alpha-1 blockers and the possibility of a class effect cannot be excluded. As IFIS may lead to increased procedural complications during the cataract operation, current or past use of alpha-1 blockers should be made known to the ophthalmic surgeon in advance of surgery.
Effects on Ability to Drive and Use Machines: The use of Labetalol hydrochloride tablets is unlikely to result in any impairment of the ability of patients to drive or operate machinery. However, it should be taken into account that occasionally dizziness or fatigue may occur.
This is considered not relevant for Labetalol hydrochlo­ride injection, as the injection is intended for i.v. use in hospitalised patients only.
Use In Pregnancy & Lactation
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.
In humans, Labetalol 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, hypoglycaemia, hypothermia) has been rarely reported. Sometimes these symptoms developed a day or two after birth. Response to supportive measure (e.g.i.v. fluids and glucose) is usually prompt but with severe preeclampsia, particularly after prolonged i.v. Labetalol hydrochloride, recovery may be slower. This may be related to diminished liver metabolism in premature babies. Intra-uterine and neonatal deaths have been reported but other drugs (e.g. vasodilators, respiratory depressants) and the effects of pre-eclampsia, intra- uterine growth retardation and prematurity were implicated. Such clinical experience warns against unduly prolonging high dose Labetalol hydrochloride and delaying delivery and against co-administration of Hydralazine.
Labetalol is excreted in breast milk: no adverse effects in breast feeding infants have been reported.
Adverse Reactions
Labetalol hydrochloride injection is usually well tolerated. Most adverse effects have been mild and transient. Symptomatic postural hypotension is likely to occur if patients are tilted or allowed to assume the upright position within 3 hours of receiving Labetalol hydrochloride Injection.
The following also were reported with Labetalol hydrochloride injection: Cardiovascular System: Ventricular arrhythmia.
Central and Peripheral Nervous System: 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.
In addition, a number of other less common adverse events have been reported: Cardiovascular: 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.
Drug Interactions
Labetalol hydrochloride injection may enhance the hypotensive effects of halothane.
Care should be taken if Labetalol is used concomitantly with either Class I antiarrhythmic agents or calcium antagonists of the verapamil type.
The hypotensive effect of Labetalol hydrochloride injection may be reduced when used in combination with prostaglandin synthetase inhibitors (NSAIDs). Dosage adjustments may therefore be necessary.
Labetalol hydrochloride injection fluoresces in alkaline solution at an excitation wavelength of 334 nm and a fluorescence wavelength of 412 nm and may therefore interfere with the assays of certain fluorescent substances including catecholamines.
The presence of Labetalol metabolites in the urine may result in falsely elevated levels or urinary catecholamines, Metanephrine, Normetanephrine, and Vaillylmandelic acid (VMA) when measured by fluorimetric or photometric methods. In screening patients suspected of having a pheochromocytoma and being treated with Labetalol hydrochloride, a specific method, such as a high performance liquid chromatographic assay with solid phase extraction should be employed in determining levels of catecholamines.
Labetalol has been shown to reduce the uptake of radioisotopes of Metaiodobenzylguanidine (MIBG). Care should therefore be taken in interpreting results from MIBG scintigraphy.
Labetalol hydrochloride injection may enhance digoxin's effect of reducing ventricular rate.
Concomitant administration of Labetalol with Adrenaline may result in bradycardia and hypertension.
Incompatibilities: Pharmaniaga Labetalol hydrochloride 25mg/5mL Injection is incompatible with Sodium bicarbonate injection 4.2% W/V.
Storage
Store below 30°C.
Do not freeze. Protect from light.
The solution will remain stable for 24 hours at 25°C after mixing with the compatible solutions. Unused admixtures should be discarded 24 hours after preparation.
MIMS Class
ATC Classification
C07AG01 - labetalol ; Belongs to the class of alpha and beta blocking agents. Used in the treatment of cardiovascular diseases.
Presentation/Packing
Inj 25 mg/5 mL (clear, colourless to pale yellow solution in amp) x 10's.
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