Labiject ®

Severe hypertension

Bolus injection:

If it is essential to reduce blood pressure quickly, a dose of 50mg of labetalol hydrochloride should be given by intravenous injection (over a period of at least one minute) and, if necessary, may be repeated at five-minute intervals until a satisfactory response occurs. The total dosage should not exceed 200mg.

The maximum effect usually occurs within five minutes and the effective duration of action is usually about 6 hours but may be as long as 18 hours.

Intravenous infusion:

(instructions for dilution)

A labetalol infusion solution containing 1mg/ml needs to be used. This solution can be made by diluting the contents of four 10ml ampoules (200mg) to 200ml with Sodium Chloride and Dextrose Injection, 5% dextrose Intravenous Infusion, Potassium Chloride and Glucose solution or Ringer Lactate.

The rate of infusion of Labetalol hydrochloride should be about 160mg/hour, but may be adjusted according to the response at the discretion of the physician. The effective dose is usually in the range of 50-200mg but infusion needs to be administered until a satisfactory result has been achieved. A larger dose may be required, especially in patients with phaeochromocytoma.

 

In severe cases of hypertension of pregnancy, a lower, increasing infusion rate needs to be administered. The infusion needs to be started at the rate of 20mg/ hour, and this dose may be doubled every 30 minutes until a satisfactory result has been obtained, or a dosage of 160mg/hour is reached.

Contraindications:

• Non-selective beta blockers must not be used on patients with a history of asthma or a history of obstructive pulmonary disease
• Labetalol injections are contraindicated for second or third-degree heart block (unless a pacemaker is in-situ), cardiogenic shock and other disorders which are associated with serious and long-lasting hypotension and/or bradycardia.
• Decompensated heart failure
• Uncontrolled/ unstable heart failure.
• Sick sinus syndrome (including sino-atrial block), unless a pacemaker is in-situ
• Prinzmetal’s angina.
• Sinus node dysfunction
• Hypersensitivity to the active substance, or any of the excipients.

Interactions:

The hypotensive effect of Labetalol may be reduced when used in combination with prostaglandin synthetase inhibiting drugs (NSAID’s, nonsteroidal anti-inflammatory drugs). Dose adjustments may be necessary. The combination with other antihypertensives may lead to additive synergism.

Labetalol is fluorescent in alkaline solution with an excitation wavelength of 334 nanometer and a fluorescent wavelength of 412 nanometer, and may therefore interfere with the tests of some fluorescent substances, including catecholamines.

The presence of labetalol metabolites in the urine can lead to false high levels of catecholamines, metanephrines, normetanephrines, and vanillylmandelic acid (VMA) in the urine when measured with fluorimetric or photometric methods. When patients who are suspected to suffer from phaeochromocytoma are screened, and are treated with labetalol hydrochloride, a specific method such as HPLC-assay with solid phase extraction will need to be used to determine the level of catecholamines.

Pregnancy and Lactation:

Pregnancy:

On the basis of experience during human pregnancy, it is unexpected that labetalol increases the risk of birth defects. Animal studies have not demonstrated reproductive toxicity. However, toxicity has been demonstrated in embryo-foetal development. Labetalol crosses the placenta barrier and because of the pharmacological activity of alpha- and beta- adreneceptor blockade, side effects in the foetus and neonate should be borne in mind (bradycardia, hypotension, respiratory depression, hypoglycemia, hypothermia). Close observation up to 24 to 48 hours after birth is required. Beta-blockers may reduce placental perfusion.

Labetalol should only be used during the pregnancy if the potential benefit for the mother outweighs the potential risk for the fetus.

Breast-feeding:

Labetalol is excreted in breast milk in small amounts (approximately 0.004-0.07% of the dose administered to the mother). No side-effects have been reported. Monitoring is needed if Labetalol is used in lactating mothers.

Warning and Precaution:

Liver Disease

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. There have been reports of fatal hepatic necrosis. 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.

Extra caution needs to be taken when labetalol is used in patients with liver dysfunction, as these patients metabolize labetalol slower than patients without liver dysfunction.

Renal impairment

Caution needs to be taken when Labetalol is used in patients with severe renal impairment (GFR = 15 – 29 ml/min/1,73 m2).

Peripheral circulatory disorders

Labetalol should be used with great caution in patients with peripheral circulatory disorders as aggravation of these disorders may occur. Great caution is advised in patients with peripheral arterial diseases (Raynaud’s disease or syndrome, intermittent claudication), as aggravation of these disorders may occur. Alpha blockers may counteract the adverse effects of beta blockers.

Symptomatic Bradycardia

If the patient experiences symptoms related to bradycardia, the dosage of Labetalol should be reduced.

First degree atrioventricular block

Due to the negative effect of beta-adrenergic blocking agents on the atrioventricular conduction time, labetalol needs to be administered with caution to patients with first degree atrioventricular block

Diabetes Mellitus

Great caution needs to be taken with untreated or uncontrolled diabetes mellitus. As with other beta-adrenergic blocking agents, labetalol can mask the symptoms of hypoglycemia (tachycardia and tremor) in diabetic patients. The hypoglycemic effect of insulin and oral hypoglycemic agents can be higher when beta-adrenergic blocking agents are used.

Adverse Reactions:

Postural hypotension/dizziness, fatigue, headache, rashes, impotence, urinary retention, gastrointestinal problems, asthma, Raynaud’s phenomenon, and heart failure.

Storage:

Store below 30 and protect from light and moisture.