LABETALOL

What it is

Labetalol SXP is a labetalol hydrochloride solution for injection containing 50 mg of labetalol hydrochloride in 10 mL of solution. It is a clear, colourless sterile solution for injection intended for parenteral intravenous administration presented in 10.8 mL clear, type 1 glass ampoules. The solution is preservative-free. Labetalol lowers blood pressure primarily by blocking peripheral arteriolar alpha-adrenoceptors, thus reducing peripheral resistance, and by concurrent beta-blockade protects the heart from reflex sympathetic drive that would otherwise occur. Labetalol antagonises alpha- and beta-adrenoceptors concurrently by competitive inhibition; it has no intrinsic sympathomimetic activity and the beta-blockade is non-selective.

Approved indications

— The emergency treatment of severe hypertension when prompt and urgent reduction of blood pressure is essential.

Dosing overview

Labetalol hydrochloride solution for injection is intended for intravenous use in hospitalised patients, with initial treatment by slow intravenous bolus injection over about 2 minutes, commencing with a 20 mg dose. Blood pressure should be closely monitored and, if necessary, an additional 40 mg slow bolus dose should be given 10 to 20 minutes after the initial dose. Up to a further 3 × 80 mg slow bolus doses may be given at 10 to 20 minute intervals if required to adequately control blood pressure. The maximum total dose given should not exceed 300 mg over a 24-hour period. If bolus treatment is unsuccessful in reducing blood pressure, patients can be commenced on an intravenous infusion of labetalol, prepared by dilution with Sodium Chloride/Dextrose Injection BP or 5% Dextrose Intravenous Infusion BP to a concentration of 1 mg/mL. In cases of severe hypertension in pregnancy, the infusion should commence at 20 mg/hr and increased by 20 mg/hr at 20 minute intervals if necessary for adequate blood pressure control, up to a maximum of 160 mg/hr. In cases of severe hypertension due to other causes, the infusion rate should be about 2 mg per minute until a satisfactory response is obtained; the effective dose is usually in the range of 50 to 200 mg depending on the severity of the hypertension.

Key safety warnings

There have been rare reports of severe hepatocellular injury with labetalol therapy, with the hepatic injury usually reversible and occurring after both short and long-term treatment. Appropriate laboratory testing should be done at the first sign or symptom of liver dysfunction, and if there is laboratory evidence of liver injury or the patient is jaundiced, labetalol therapy should be stopped and not re-started. Due to negative inotropic effects, special care should be taken with patients whose cardiac reserve is poor and heart failure should be controlled before starting labetalol therapy. Patients, particularly those with ischaemic heart disease, should not interrupt or discontinue abruptly labetalol therapy; the dosage should gradually be reduced over 1 to 2 weeks, if necessary at the same time initiating replacement therapy, to prevent exacerbation of angina pectoris. Labetalol is contraindicated in patients with asthma or a history of obstructive airways disease as beta-blockade can induce bronchospasm which is refractory to treatment with beta-adrenergic agents. While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge and may be unresponsive to the usual doses of epinephrine used to treat allergic reaction. Patients should always be kept supine during the period of intravenous drug administration; a substantial drop in blood pressure on standing should be expected, and the patient's ability to tolerate an upright position on standing should be established before permitting any ambulation.

Contraindications

Non-selective beta blockers must not be used in patients with a history of asthma or a history of obstructive pulmonary disease. Additional contraindications include bradycardia (less than 45 to 50 beats per minute); sick sinus syndrome (including sino-atrial block); second or third degree heart block; cardiogenic shock; hypersensitivity to labetalol; symptomatic heart failure; severe peripheral circulatory disturbances; metabolic acidosis; untreated phaeochromocytoma; Prinzmetal's angina; peripheral vasoconstriction suggesting low cardiac output (where labetalol injection is contraindicated to control hypertensive episodes following acute myocardial infarction); hypotension; right ventricular failure secondary to pulmonary hypertension; and significant right ventricular hypertrophy.

Regulatory history

The TGA approved labetalol SXP/RMB/TLB (labetalol hydrochloride) 50 mg/10 mL solution for injection on 23 August 2019. The approval was based on a literature-based submission, with the TGA concluding that the clinical data adequately supported the proposed indication for the emergency treatment of severe hypertension and that the efficacy and safety of intravenous labetalol for this indication are well-established in the literature. The product was first listed on the ARTG on 14 November 2019.