Among patients dosed with labetalol hydrochloride tablets, there have been reversible increases of serum transaminases in 4% of patients tested and, more rarely, reversible increases in blood urea.
Overdosage with labetalol HCl 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 HCl follows oral ingestion, gastric lavage or pharmacologically induced emesis (using syrup of ipecac) may be 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 pharmacologic evidence that norepinephrine may be the drug of choice.
Bronchospasm —administer epinephrine and/or an aerosolized beta 2 -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 mg to 10 mg rapidly over 30 seconds, followed by continuous infusion of 5 mg/h that can be reduced as the patient improves).
Neither hemodialysis nor peritoneal dialysis removes a significant amount of labetalol from the general circulation (<1%).
The oral LD 50 value of labetalol HCl in the mouse is approximately 600 mg/kg and in the rat is greater than 2 g/kg. The intravenous LD 50 in these species is 50 mg/kg to 60 mg/kg.
Labetalol hydrochloride injection is intended for intravenous use in hospitalized patients. DOSAGE MUST BE INDIVIDUALIZED depending upon the severity of hypertension and the response of the patient during dosing.
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. The patient’s ability to tolerate an upright position should be established before permitting any ambulation, such as using toilet facilities.
Either of two methods of administration of labetalol hydrochloride injection may be used: a) repeated intravenous injection, or b) slow continuous infusion.
Initially, labetalol hydrochloride injection should be given in a 20 mg dose (which corresponds to 0.25 mg/kg for an 80 kg patient) by slow intravenous injection over a 2 minute period.
Immediately before the injection and at 5 minutes and 10 minutes after injection, supine blood pressure should be measured to evaluate response. Additional injections of 40 mg 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 HCl has been injected. The maximum effect usually occurs within 5 minutes of each injection.
Labetalol hydrochloride injection is prepared for continuous intravenous infusion by diluting the vial contents with commonly used intravenous fluids (see below). Examples of two methods of preparing the infusion solution are:
Add 40 mL of labetalol hydrochloride injection to 160 mL of a commonly used intravenous fluid such that the resultant 200 mL of solution contains 200 mg of labetalol HCl, 1 mg/mL. The diluted solution should be administered at a rate of 2 mL/min to deliver 2 mg/min.
Alternatively, add 40 mL of labetalol hydrochloride injection to 250 mL of a commonly used intravenous fluid. The resultant solution will contain 200 mg of labetalol HCl, approximately 2 mg/3 mL. The diluted solution should be administered at a rate of 3 mL/min to deliver approximately 2 mg/min.
The rate of infusion of the diluted solution may be adjusted according to the blood pressure response, at the discretion of the physician. To facilitate a desired rate of infusion, the diluted solution can be infused using a controlled administration mechanism, e.g., graduated burette or mechanically driven infusion pump.
Since the half-life of labetalol is 5 to 8 hours, steady-state blood levels (in the face of a constant rate of infusion) would not be reached during the usual infusion time period. The infusion should be continued until a satisfactory response is obtained and should then be stopped and oral labetalol HCl started (see below). The effective intravenous dose is usually in the range of 50 mg to 200 mg. A total dose of up to 300 mg may be required in some patients.
The blood pressure should be monitored during and after completion of the infusion or intravenous injection. 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 the response of the diastolic pressure.
Subsequent oral dosing with labetalol hydrochloride tablets should begin when it has been established that the supine diastolic blood pressure has begun to rise. The recommended initial dose is 200 mg, followed in 6 to 12 hours by an additional dose of 200 mg or 400 mg, depending on the blood pressure response. Thereafter, inpatient titration with labetalol hydrochloride tablets may proceed as follows:
Daily Dose *
200 mg b.i.d.
400 mg b.i.d.
800 mg b.i.d.
1,200 mg b.i.d.
The dosage of labetalol hydrochloride tablets used in the hospital may be increased at 1-day intervals to achieve the desired blood pressure reduction.
For subsequent outpatient titration or maintenance dosing, see DOSAGE AND ADMINISTRATION in the Labetalol Hydrochloride Tablets Product Information for additional recommendations.
Parenteral drug products should be inspected visually for particulate matter and discoloration before administration whenever solution and container permit.
Labetalol hydrochloride injection was tested for compatibility with commonly used intravenous fluids at final concentrations of 1.25 mg to 3.75 mg of labetalol HCl per milliliter of the mixture. Labetalol hydrochloride injection was found to be compatible with and stable (for 24 hours refrigerated or at room temperature) in mixtures with the following solutions: ringer’s injection, USP; lactated ringer’s injection, USP; 5% dextrose and ringer’s injection; 5% lactated ringer’s and 5% dextrose injection; 5% dextrose injection, USP; 0.9% sodium chloride injection, USP; 5% dextrose and 0.2% sodium chloride injection, USP; 2.5% dextrose and 0.45% sodium chloride injection, USP; 5% dextrose and 0.9% sodium chloride injection, USP; and 5% dextrose and 0.33% sodium chloride injection, USP.
Labetalol hydrochloride injection was NOT compatible with 5% sodium bicarbonate injection, USP. Care should be taken when administering alkaline drugs, including furosemide, in combination with labetalol. Compatibility should be assured prior to administering these drugs together.
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