Labetalol Hydrochloride is indicated for the control of all grades of hypertension including-
- Pregnancy-induced hypertension
- The treatment of angina in patients with hypertension
- Where a hypertensive technique is indicated in anesthesia
- The management of catecholamine excess and patients with pheochromocytoma.
Labetalol competitively inhibits the adrenergic stimulation of β-receptors within the myocardium, bronchial and vascular smooth muscle, and α1-receptors w/in vascular smooth muscle. It also has some intrinsic β2-agonist and membrane-stabilising activity.
The capacity of labetalol HCl to block alpha receptors in man has been demonstrated by attenuation of the pressor effect of phenylephrine and by a significant reduction of the pressor response caused by immersing the hand in ice-cold water (“cold-pressor test”). Labetalol HCl’s beta1-receptor blockade in man was demonstrated by a small decrease in the resting heart rate, attenuation of tachycardia produced by isoproterenol or exercise, and by attenuation of the reflex tachycardia to the hypotension produced by amyl nitrite. Beta2-receptor blockade was demonstrated by inhibition of the isoproterenol-induced fall in diastolic blood pressure. Both the alpha- and beta-blocking actions of orally administered labetalol HCl contribute to a decrease in blood pressure in hypertensive patients. Labetalol HCl consistently, in dose-related fashion, blunted increases in exercise-induced blood pressure and heart rate, and in their double product. The pulmonary circulation during exercise was not affected by labetalol HCl dosing.
Single oral doses of labetalol HCl administered to patients with coronary artery disease had no significant effect on sinus rate, intraventricular conduction, or QRS duration. The atrioventricular (A-V) conduction time was modestly prolonged in two of seven patients. In another study, IV labetalol HCl slightly prolonged A-V nodal conduction time and atrial effective refractory period with only small changes in heart rate. The effects on A-V nodal refractoriness were inconsistent.
Labetalol HCl produces dose-related falls in blood pressure without reflex tachycardia and without significant reduction in heart rate, presumably through a mixture of its alpha- and beta-blocking effects. Hemodynamic effects are variable, with small, nonsignificant changes in cardiac output seen in some studies but not others, and small decreases in total peripheral resistance. Elevated plasma renins are reduced.
Dosage & Administration
Adult: The recommended initial dosage is 100 mg twice daily whether used alone or added to a diuretic regimen. After 2 or 3 days, using standing blood pressure as an indicator, dosage may be titrated in increments of 100 mg b.i.d. every 2 or 3 days. The usual maintenance dosage of labetalol HCl is between 200 and 400 mg twice daily.
Since the full antihypertensive effect of labetalol HCl is usually seen within the first 1 to 3 hours of the initial dose or dose increment, the assurance of a lack of an exaggerated hypotensive response can be clinically established in the office setting. The antihypertensive effects of continued dosing can be measured at subsequent visits, approximately 12 hours after a dose, to determine whether further titration is necessary.
Patients with severe hypertension may require from 1,200 to 2,400 mg per day, with or without thiazide diuretics. Should side effects (principally nausea or dizziness) occur with these doses administered twice daily, the same total daily dose administered three times daily may improve tolerability and facilitate further titration. Titration increments should not exceed 200 mg twice daily.
When a diuretic is added, an additive antihypertensive effect can be expected. In some cases this may necessitate a labetalol HCl dosage adjustment. As with most antihypertensive drugs, optimal dosages of Labetalol Tablets are usually lower in patients also receiving a diuretic.
When transferring patients from other antihypertensive drugs, Labetalol Tablets should be introduced as recommended and the dosage of the existing therapy progressively decreased.
Elderly: As in the general patient population, labetalol therapy may be initiated at 100 mg twice daily and titrated upwards in increments of 100 mg b.i.d. as required for control of blood pressure. Since some elderly patients eliminate labetalol more slowly, however, adequate control of blood pressure may be achieved at a lower maintenance dosage compared to the general population. The majority of elderly patients will require between 100 and 200 mg b.i.d.
- Bolus Injection: If it is essential to reduce the blood pressure quickly a dose of 50 mg should be given by intravenous injection (over a period of at least one minute) and, if necessary, repeated at five minute intervals until a satisfactory response occurs. The total dose should not exceed 200 mg.
- Intravenous Infusion: For intravenous infusion the injection should be diluted with a suitable intravenous infusion fluid to a concentration of Labetalol Hydrochloride 1 mg/1 ml. Compatible fluids include 5% Dextrose; 0.9% Sodium Chloride; Dextrose and Sodium Chloride.
- Hypertension in pregnancy: Infusion should be started at 20 mg/hour, then doubled every 30 minutes until a satisfactory response is obtained or a dosage of 160 mg/hour is reached.
- Hypertensive episodes following acute myocardial infarction: Infusion should be started at 15 mg/hour and gradually increased to a maximum of 120 mg/hour depending on the control of blood pressure.
- Hypertension due to other causes: Infuse at a rate of about 2 mg/min until a satisfactory response is obtained, then stop infusion. The effective dose is usually 50-200 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. Labetalol injection has been administered to patients with uncontrolled hypertension already receiving other hypotensive agents, including b-blocking drugs, without adverse effects.
- 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 injection is 10-20 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 (25-30 mg). If satisfactory hypotension is not achieved after five minutes, increments of 5-10 mg should be given until the desired level of blood pressure is attained. Halothane and Labetalol act synergistically therefore the halothane concentration should not exceed 1-1.5% as profound falls in blood pressure may be precipitated.
Children: Safety and efficacy in children have not been established.
Pregnancy & Lactation
Pregnancy Category C. Teratogenic studies were performed with labetalol in rats and rabbits at oral doses up to approximately six and four times the maximum recommended human dose (MRHD), respectively. No reproducible evidence of fetal malformations was observed. Increased fetal resorptions were seen in both species at doses approximating the MRHD. A teratology study performed with labetalol in rabbits at IV doses up to 1.7 times the MRHD revealed no evidence of drug-related harm to the fetus. 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.
Nonteratogenic Effects: Hypotension, bradycardia, hypoglycemia, and respiratory depression have been reported in infants of mothers who were treated with labetalol HCl for hypertension during pregnancy. Oral administration of labetalol to rats during late gestation through weaning at doses of two to four times the MRHD caused a decrease in neonatal survival.
Labor and Delivery: Labetalol HCl given to pregnant women with hypertension did not appear to affect the usual course of labor and delivery.
Nursing Mothers: Small amounts of labetalol (approximately 0.004% of the maternal dose) are excreted in human milk. Caution should be exercised when Labetalol Tablets are administered to a nursing woman.