PRESOLOL

What it is

PRESOLOL is 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. 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.

Approved indications

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

Dosing overview

PRESOLOL is intended for intravenous use in hospitalised patients, with dosage individualised depending on the severity of hypertension and the response of the patient during dosing. **Bolus dosing:** Initial treatment should be by slow intravenous bolus injection over about 2 minutes, commencing with a 20 mg dose. If necessary, an additional 40 mg slow bolus dose should be given 10–20 minutes after the initial dose. Up to a further 3 × 80 mg slow bolus doses may be given at 10–20 minute intervals if required to adequately control blood pressure. The maximum total dose given should not exceed 300 mg over a 24-hour period. **Intravenous infusion:** 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 rate of infusion should be about 2 mg per minute, until a satisfactory response is obtained; the effective dose is usually in the range of 50–200 mg depending on the severity of the hypertension.

Key safety warnings

There have been rare reports of severe hepatocellular injury with labetalol therapy. The hepatic injury is usually reversible and has occurred 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 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 ischemic heart disease, should not interrupt or discontinue abruptly labetalol therapy. The dosage should gradually be reduced, over 1–2 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. In such cases the risk of inducing bronchospasm should be appreciated and appropriate precautions taken. Patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge while taking beta-blockers, either accidental, diagnostic or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.

Contraindications

Non-selective beta blockers must not be used on patients with a history of asthma or a history of obstructive pulmonary disease. Additional contraindications include bradycardia (less than 45–50 bpm), 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, hypotension, right ventricular failure secondary to pulmonary hypertension, and significant right ventricular hypertrophy. Where peripheral vasoconstriction suggests low cardiac output, the use of labetalol injection to control hypertensive episodes following acute myocardial infarction is contraindicated.

PBS listing

The labetalol hydrochloride 100 mg tablet is listed on the PBS with 2 items under a restricted listing, with an ex-manufacturer price of A$16.43.

Regulatory history

PRESOLOL 100 mg and PRESOLOL 200 mg tablets were first listed on the ARTG on 19 July 1996. The current injection formulation was first approved on 23 August 2019.