Consumer medicine information

Presolol

Labetalol hydrochloride

BRAND INFORMATION

Brand name

Presolol

Active ingredient

Labetalol hydrochloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Presolol.

What is in this leaflet

This leaflet answers some common questions about PRESOLOL. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking PRESOLOL against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, talk to your doctor or pharmacist.

Keep this leaflet with your medicine. You may need to read it again.

What PRESOLOL is used for

PRESOLOL contains the active ingredient labetalol hydrochloride and is used to lower high blood pressure, also called hypertension.

Everyone has blood pressure. This pressure helps to circulate your blood all around your body. Your blood pressure may be different during different times of the day, depending on how busy or worried you are. You have hypertension (high blood pressure) when your blood pressure stays higher than normal, even when you are calm and relaxed.

There are usually no symptoms of hypertension. The only way of knowing that you have hypertension is to have your blood pressure checked on a regular basis. You may feel fine and have no symptoms, but if high blood pressure is not treated it can lead to serious health problems.

This medicine belongs to a group of medicines called beta-blockers. These medicines work by changing the body's response to some nerve impulses. As a result, it widens blood vessels in the body causing blood pressure to fall.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed PRESOLOL for another reason.

There is not enough information to recommend the use of this medicine in children. Safety and effectiveness have not been established in this age group.

This medicine is available only with a doctor's prescription.

There is no evidence that PRESOLOL is addictive.

Before you take PRESOLOL

When you must not take it

Do not take PRESOLOL if you have an allergy to:

  • any medicine containing labetalol hydrochloride
  • any of the ingredients listed at the end of this leaflet
  • any other beta-blocker medicines

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin

Do not take PRESOLOL if you have:

  • asthma, wheezing, difficulty breathing or other lung problems, or if you have had them in the past
  • a history of allergic problems, including hayfever
  • a very slow heart beat, less than 45-50 beats per minute
  • certain other heart conditions

Do not take this medicine if you are pregnant. PRESOLOL is not recommended for use during the first trimester of pregnancy as it may affect your developing baby.

If it is necessary for you to take PRESOLOL later in pregnancy, your doctor will discuss with you the risks and benefits involved.

Do not breast-feed if you are taking this medicine. The active ingredient in PRESOLOL passes into breast milk and there is a possibility that your baby may be affected.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, dyes or preservatives.

Tell your doctor if you have or have had any of the following medical conditions:

  • diabetes
  • breathing problems such as asthma
  • kidney problems
  • liver problems such as jaundice
  • an overactive thyroid
  • any blood vessel disorders causing poor circulation in the arms and legs
  • phaeochromocytoma, a rare tumour of the adrenal gland
  • certain types of angina, such as Prinzmetal angina or variant angina
  • shock or severe low blood pressure
  • heart failure any other heart problems

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding. Your doctor can discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell them before you start taking PRESOLOL.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and PRESOLOL may interfere with each other. These include:

  • other beta-blocker medicines, including beta-blocker containing eye drops
  • calcium channel blockers, medicines used to treat high blood pressure and angina, such as verapamil, diltiazem
  • certain medicines used to treat an irregular heartbeat, such as disopyramide, quinidine
  • other blood pressure medication, such as clonidine, methyldopa
  • fluid tablets, also called diuretics
  • cimetidine, a medicine commonly used to treat stomach ulcers
  • some medicines used to treat depression
  • insulin and other medicines used to treat diabetes
  • guanethidine, a medicine used to treat certain heart conditions
  • some medicines used during surgery and emergency situations such as anaesthetics
  • non-steroidal anti-inflammatory drugs (NSAIDs), a group of medicines used to treat arthritis, pain or inflammation, such as ibuprofen, indometacin, aspirin

These medicines may be affected by PRESOLOL or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How to take PRESOLOL

Follow all directions given to you by your doctor and pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the bottle, ask your doctor or pharmacist for help.

How much to take

The dose of PRESOLOL varies from patient to patient.

The usual adult starting dose is 100 mg to 200 mg twice daily.

Your doctor may change this dose depending on how you respond to this medicine. Your doctor will decide the right dose for you.

Elderly patients may need smaller doses.

This medicine is not recommended for use in children.

How to take it

Swallow the tablets whole with a glass of water.

When to take it

Take your medicine immediately after meals. Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

How long to take it

Continue taking your medicine for as long as your doctor tells you.

This medicine helps to control your condition but does not cure it. It is important to keep taking your medicine even if you feel well.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take the missed dose as soon as you remember, and then go back to taking your medicine as you would normally.

Do not take a double dose to make up for the dose you missed. This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering when to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at the nearest hospital if you think that you or anyone else may have taken too much PRESOLOL. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If you have taken too much PRESOLOL, you may feel nausea, vomiting, dizziness, lightheaded, faintness and a very slow heart beat.

While you are taking PRESOLOL

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking PRESOLOL.

Tell any other doctors, dentists and pharmacists who treat you that you are taking this medicine.

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine. It may affect other medicines used during surgery.

If you become pregnant while taking this medicine, tell your doctor immediately.

If you have a severe allergic reaction to foods, medicines or insect stings, tell your doctor immediately. If you have a history of allergies, there is a chance that PRESOLOL may make allergic reactions worse and harder to treat.

Immediately stop taking this medicine if a skin rash or any other allergic reaction occurs.

If you are being treated for diabetes, make sure you check your blood sugar level regularly. PRESOLOL may affect how well your diabetes is controlled. It may also hide some of the symptoms of low blood sugar (also called hypoglycaemia) such as a fast heart beat. PRESOLOL may also make low blood sugar last longer.

Your doctor may need to change your dose of diabetic medicines, including insulin.

If you are about to have any blood tests, tell your doctor that you are taking this medicine. It may interfere with the results of some tests.

Keep all of your doctor's appointments so that your progress can be checked.

Things you must not do

Do not take PRESOLOL to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as you.

Do not stop taking your medicine or change the dosage without checking with your doctor. Stopping PRESOLOL suddenly may cause unwanted heart problems. Your doctor may want you to gradually reduce the amount of Presolol you are taking before stopping completely. This may help reduce the possibility of heart complications from occurring.

Things to be careful of

Be careful driving or operating machinery until you know how PRESOLOL affects you. This medicine may cause drowsiness, dizziness or lightheadedness in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

If you feel light-headed, dizzy or faint when getting out of bed or standing up, get up slowly. Standing up slowly, especially when you get up from bed or chairs, will help your body get used to the change in position and blood pressure. If this problem continues, or gets worse, talk to your doctor

Make sure you drink enough water in hot weather and during exercise when you are taking this medicine, especially if you sweat a lot. If you do not drink enough water while taking PRESOLOL, you may feel faint, lightheaded or sick (nauseous). This is because your blood pressure is dropping suddenly.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking PRESOLOL.

This medicine helps most people with high blood pressure, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

If you are over 65 years of age, you may have an increased chance of getting side effects.

Do not be alarmed by the following list of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • dizziness or lightheadedness, especially when getting up quickly
  • tiredness, lack of energy
  • headache
  • trembling, muscle cramps
  • unusual movements, including tremors
  • depressed mood
  • tingling of the skin, especially the scalp
  • dry, red or sore eyes, blurred vision
  • nausea, feeling sick, vomiting, upset stomach
  • fever or chills
  • increased sweating
  • blocked nose
  • problems with sexual function
  • swelling of the ankles

Tell your doctor as soon as possible if you notice any of the following:

  • slow or irregular heart beat
  • feeling generally unwell, sometimes with yellowing of the eyes or skin (jaundice)
  • difficulty in passing urine or unable to pass urine
  • any type of skin rash, redness, itching or hives.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • chest tightness, wheezing, shortness of breath
  • swelling of the face, lips, mouth or throat which may cause difficulty in swallowing or breathing

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

After taking PRESOLOL

Storage

Keep your tablets in the bottle until it is time to take them. If you take the tablets out of the bottle they may not keep well.

Keep your tablets in a cool dry place where the temperature stays below 30°C.

Do not store PRESOLOL or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine, or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

PRESOLOL is available in 2 strengths of tablets:

  • PRESOLOL 100 - round orange tablet marked LL 100 on one side and G on the other side
  • PRESOLOL 200 - round orange tablet marked LL 200 on one side and G on the other side

Each bottle contains 100 tablets.

Ingredients

PRESOLOL contains either 100 mg or 200 mg of labetalol hydrochloride as the active ingredient

The tablets also contain the following inactive ingredients:

  • microcrystalline cellulose
  • magnesium stearate
  • colloidal anhydrous silica
  • silicon dioxide
  • sodium starch glycollate
  • pregelatinised maize starch
  • sucrose
  • Opadry Orange OY-LS-23015

PRESOLOL contains sulfites, lactose and sugars. The tablets are gluten free.

Manufacturer

PRESOLOL is made in Australia by:

Alphapharm Pty Limited
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.mylan.com.au

Australian registration numbers:

PRESOLOL 100 - AUST R 56475

PRESOLOL 200 - AUST R 56476

This leaflet was prepared in October 2019.

presolol_cmi\Oct19/00

Published by MIMS December 2019

BRAND INFORMATION

Brand name

Presolol

Active ingredient

Labetalol hydrochloride

Schedule

S4

 

1 Name of Medicine

Labetalol hydrochloride.

6.7 Physicochemical Properties

Labetalol hydrochloride is a white to off-white, practically odourless powder. Melting point is about 180°C.
Chemical name: 2-hydroxy-5- [1-hydroxy-2- (1-methyl-3- phenylpropylamino) ethyl] benzamide hydrochloride.
Molecular formula: C19H24N2O3HCl.
Molecular weight: 364.9.

Chemical structure.


CAS number.

32780-64-6.

2 Qualitative and Quantitative Composition

Each film coated tablet contains 100 mg or 200 mg of labetalol hydrochloride as the active ingredient.

Excipients of known effect.

Lactose monohydrate, sugars and sulfites.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Presolol 100: orange film coated tablet, marked LL/100 on one side, G on reverse.
Presolol 200: orange film coated tablet, marked LL/200 on one side, G on reverse.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Labetalol antagonises alpha- and beta-adrenoreceptors concurrently by competitive inhibition; it has no intrinsic sympathomimetic activity and less pronounced membrane stabilising activity than propranolol. The beta-blockade is nonselective. Labetalol has two centres of chirality which means that four isomers are possible, each of the isomers having different relative alpha- and beta-blocking activities.
Labetalol lowers blood pressure by blocking alpha-adrenoreceptors in peripheral arterioles and thereby reducing peripheral resistance. Labetalol also concurrently blocks beta-adrenoreceptors, notably in the heart, from the reflexly mediated drive caused by the peripheral vasodilatation. Therefore, the reduction in blood pressure is achieved without cardiac stimulation. Labetalol does not reduce cardiac output at rest, or after moderate exercise. Normally occurring increases in systolic pressure during exercise are, however, lessened by labetalol; corresponding changes in the diastolic pressure are not affected.
The precise relationship between alpha- and beta-blocking effects in contributing to the antihypertensive action is unknown. At therapeutic doses, labetalol is less active at alpha-adrenoreceptors than beta-adrenoreceptors, and adequate vasodilatation is achieved with incomplete blockade of the alpha-adrenoreceptors in the arterioles. The barostatic reflexes remain sufficiently active to prevent postural and exercise hypotension in most patients, but this phenomenon has been observed at all doses and becomes more common in patients with severe hypertension on large doses of the drug.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Taken orally, Presolol tablets are well absorbed.
The absolute bioavailability of labetalol is increased when administered with food.

Metabolism.

The drug is extensively metabolised by the liver, and possibly in the gut wall, to O-phenyl-glucuronide, N-glucuronide and a glucuronide formed by conjugation at the secondary alcohol group. Peak plasma levels occur at 1 to 2 hours, associated with a reduction in blood pressure. On average, 35 to 40% of an administered dose reaches the circulation.
The plasma half-life is approximately 6 to 8 hours, but a hypotensive effect has been observed up to 11 hours after a given dose.
At therapeutic concentrations, the active drug binds to albumin (52%). Binding also occurs to melanin (0.05%) but the clinical significance is uncertain.

Excretion.

Labetalol and its inactive metabolites are excreted by both the liver and the kidneys, so the drug is unlikely to accumulate in the body.

Pharmacokinetics in special populations.

Whilst impairment of renal function does not require a change in dosage, impairment of hepatic function requires a reduction in dosage, due to the decrease in first-pass metabolism of the drug.
Labetalol does not adversely affect renal function and is a particularly suitable drug for use in hypertensive patients with renal disease.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

Treatment of all grades of hypertension.

4.3 Contraindications

Beta-blockers are usually contraindicated in a variety of conditions and as labetalol has not yet been fully investigated for its effect on these conditions, they should be treated as contraindications until further information is available.
1. Bronchospasm. Beta-adrenergic blockade of the smooth muscle of bronchi and bronchioles may result in an increased airways resistance. These drugs also reduce the effectiveness of asthma treatment. This may be dangerous in susceptible patients. Therefore, beta-blockers are contraindicated in any patient with a history of airways obstruction or a tendency to bronchospasm. Use of cardioselective beta-blockers can also result in severe bronchospasm. If such therapy must be used, great caution should be exercised. Alternative therapy should be considered.
2. Allergic disorders (including allergic rhinitis) which may suggest a predisposition to bronchospasm.
3. Right ventricular failure secondary to pulmonary hypertension.
4. Significant right ventricular hypertrophy.
5. Sinus bradycardia (less than 45 to 50 beats/minute) or sick sinus syndrome.
6. Second and third degree A-V block.
7. Shock (including cardiogenic and hypovolaemic shock).
8. Known hypersensitivity to labetalol hydrochloride.
9. Congestive heart failure.
10. Anaesthesia with agents that produce myocardial depression (e.g. ether, chloroform, cyclopropane).
11. Lactation and early pregnancy (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy, Use in lactation).

4.4 Special Warnings and Precautions for Use

1. Cardiac failure.

Beta-blockade depresses myocardial contractility and may precipitate cardiac failure in some patients with a history of cardiac failure, chronic myocardial insufficiency or unsuspected cardiomyopathy. In patients without a history of cardiac failure, continuing depression of the myocardium may lead to cardiac failure. If cardiac failure develops, the beta-blocker should be withdrawn (see Abrupt withdrawal below).

Note.

Although congestive heart failure has been considered to be a contraindication to the use of beta-blockers, there is a growing literature on the experimental use of beta-adrenergic blocking drugs in heart failure. As further trials are needed to identify which patients are most likely to respond to which drugs, beta-blockers should not normally be prescribed for heart failure outside of specialist centres.

2. Abrupt withdrawal.

Care should be taken if beta-blockers have to be discontinued abruptly in patients with coronary artery disease. Severe exacerbation of angina and precipitation of myocardial infarction and ventricular arrhythmias has occurred following abrupt discontinuation of beta-blockade in patients with ischaemic heart disease. Therefore it is recommended that the dosage be reduced gradually over a period of about 8 to 14 days during which time the patient's progress should be assessed. The drug may be reinstituted temporarily if the angina worsens. If the drug must be withdrawn abruptly, close observation is required. In the perioperative period, beta-blockers should not be withdrawn, unless there are strong clinical reasons to do so.

3. Concomitant therapy with calcium antagonists.

The concomitant use of beta-blockers and calcium antagonists with myocardial depressant and sinus node activity, e.g. verapamil and, to a lesser extent, diltiazem, may cause hypotension, bradycardia and asystole. Extreme caution is required if these drugs have to be used together.
The dihydropyridine calcium antagonists (e.g. nifedipine) have a weaker myocardial depressant effect and can be administered cautiously with beta-blockers. If excessive hypotension develops, the calcium antagonist should be stopped or the dosage reduced.

4. Peripheral circulation.

Beta-blockade may impair the peripheral circulation and exacerbate the symptoms of peripheral vascular disease.

5. Antiarrhythmic drugs.

Care should be taken when prescribing beta-blockers with antiarrhythmic drugs. Interactions have been reported during concomitant beta-blocker therapy with the class IA agents disopyramide, and less frequently quinidine; class IB agents, tocainide, mexiletine and lidocaine; class IC agents, flecainide and propafenone (not available in Australia); the class III agent, amiodarone; and the class IV antiarrhythmic agents.

6. Prinzmetal angina.

There is a risk of exacerbating coronary artery spasm if patients with Prinzmetal or variant angina are treated with a beta-blocker. If this treatment is essential, it should only be undertaken in a coronary or intensive care unit.

7. Euthyroid hyperthyroxinaemia.

The effects of beta-blockers on thyroid hormone metabolism may result in elevations of serum free thyroxine (T4) levels. In the absence of any signs or symptoms of hyperthyroidism, additional investigation is necessary before a diagnosis of thyrotoxicosis can be made.

8. Hepatic injury.

Severe hepatocellular injury, confirmed by rechallenge in at least one case, occurs rarely with labetalol therapy. The hepatic injury is usually reversible, but hepatic necrosis and death have been reported. Injury has occurred after both short- and long-term treatment and may be slowly progressive despite minimal symptomatology.
Appropriate laboratory testing should be done at the first sign or symptom of hepatic dysfunction. If there is laboratory evidence of hepatic injury or the patient is jaundiced, labetalol therapy should be stopped and not restarted.

9. Beta-blockers.

Beta-blockers, even those with apparent cardioselectivity, should not be used in patients with asthma or a history of obstructive disease unless no alternative treatment is available. In such cases, the risk of inducing bronchospasm should be appreciated and appropriate precautions taken. If bronchospasm should occur after the use of Presolol, it can be treated with a beta 2-agonist by inhalation, e.g. salbutamol (the dose of which may need to be greater than the usual dose in asthma), and, if necessary, intravenous atropine 1 mg.
There have been reports of skin rashes and/or dry eyes associated with the use of beta-adrenoreceptor blocking drugs. The reported incidence is small and in most cases the symptoms have cleared when treatment was withdrawn. Gradual discontinuation of the drug should be considered if any such reaction is not otherwise explicable.

Anaesthesia and the peri-operative period.

Beta-blockade may have beneficial effects in decreasing the incidence of arrhythmias and myocardial ischaemia during anaesthesia and the postoperative period. It is currently recommended that maintenance beta-blockade be continued perioperatively. The anaesthetist must be made aware of beta-blockade because of the potential for interactions with other drugs, resulting in severe bradyarrhythmias and hypotension, the decreased reflex ability to compensate for blood loss, hypovolaemia and regional sympathetic blockade, and the increased propensity for vagal-induced bradycardia. Incidents of protracted severe hypotension or difficulty restoring normal cardiac rhythm during anaesthesia have been reported. Modern inhalational anaesthetic agents are generally well tolerated, although older agents (ether, cyclopropane, methoxyflurane, trichlorethylene) were sometimes associated with severe circulatory depression in the presence of beta-blockade.
Labetalol need not be discontinued prior to anaesthesia but patients should receive intravenous atropine prior to induction.
Synergistic effects of labetalol and halothane on cardiac output and blood pressure have been reported.

Diabetes.

Beta-blockers affect glucose metabolism and may mask some important premonitory signs of acute hypoglycaemia, such as tachycardia.
In patients with insulin or noninsulin dependent diabetes, especially labile diabetes, or with a history of spontaneous hypoglycaemia, beta-blockade may result in the loss of diabetic control and delayed recovery from hypoglycaemia. The dose of insulin or oral hypoglycaemic agent may need adjustment.
In one study there was an increase in mean fasting glucose levels during labetalol treatment but no alteration in insulin activity or response to an oral glucose tolerance test.

Other metabolic effects.

Beta-adrenoreceptors are involved in the regulation of lipid as well as carbohydrate metabolism. Some drugs affect the lipid profile adversely, although the long-term clinical significance of this change is unknown and the effect appears to be less for drugs with intrinsic sympathomimetic activity.

Use of catecholamine depleting agents.

Concomitant use of drugs such as reserpine and guanethidine requires careful monitoring since the added effect of beta-blockade may produce an excessive reduction of the resting sympathetic nervous tone.

Clonidine.

Concurrent use of beta-blockers and clonidine should be avoided because of the risk of adverse interaction and severe withdrawal symptoms. If administered concomitantly, the clonidine should not be discontinued until several days after the withdrawal of the beta-blocker.

Phaeochromocytoma.

Labetalol has been shown to be effective in lowering blood pressure and relieving symptoms in patients with phaeochromocytoma. However, paradoxical hypertension responses have been reported in a few patients with this tumour; therefore, use caution when administering labetalol to patients with phaeochromocytoma.
In patients with this condition, an alpha-blocking drug (e.g. phentolamine/ phenoxybenzamine) should be considered before administration of labetalol, bearing in mind that this drug has alpha- and beta-blocking properties (see Section 5.1 Pharmacodynamic Properties, Mechanism of action).

Eye and skin reactions.

Various skin rashes and conjunctival xeroses have been reported with beta-blockers. Cross reactions may occur between beta-blockers, therefore substitutions within the group may not necessarily preclude occurrence of symptoms.
During the long-term treatment with the beta-blocking drug, practolol, a specific rash bearing a superficial resemblance to psoriasis was occasionally described. In a number of patients affected, this rash was accompanied by adverse effects on the eye (xerophthalmia and/or keratoconjunctivitis) of varying severity. This condition is called the oculomucocutaneous syndrome or practolol syndrome. In a few patients, these eye changes occurred independently of a skin rash. On rare occasions, otitis media, sclerosing peritonitis, pericarditis and pleurisy have been reported. Although this syndrome has not been observed in patients taking other beta-blockers, the possibility of such side effects occurring should be borne in mind.
More recently an association between Peyronie's disease, a fibrosing induration of the penis, and various beta-blockers has been suggested but is not proven.
It has been found in animal studies that labetalol binds to the melanin pigment of the uveal tract. The significance of this in humans is not known but regular checks on visual function should be made as a precaution.
Extensive ophthalmological monitoring of 72 patients treated with labetalol at doses of 300 mg to 2.4 g daily for between 6 months and 3 years, and routine monitoring of eye complaints from over 6,000 patients has not revealed any adverse effects on the eye.

Sclerosing peritonitis.

Sclerosing peritonitis has been reported in association with practolol therapy but not with other beta-blockers or labetalol. Nevertheless, the possibility of such a reaction must be borne in mind.

Cross-sensitisation.

Cross sensitisation may occur between beta-blockers and substitution within the group may not necessarily preclude recurrence of symptoms.

Allergic manifestations.

These may be exaggerated by beta-blockade (e.g. allergic rhinitis during the pollen season and allergic reactions to bee and wasp stings). Beta-blockers should be avoided if there is a risk of bronchospasm.

Hyperthyroidism.

Since beta-blockers may mask the clinical signs of developing or continuing hyperthyroidism, resulting in symptomatic improvement without any change in thyroid hormone status, special care should be exercised in those patients who are hyperthyroid and are also receiving labetalol as an antihypertensive agent.

Postural hypotension.

Severe postural hypotension has occurred in some patients (see Section 4.8 Adverse Effects (Undesirable Effects)). Furthermore, this may be enhanced by the concurrent administration of other vasodilators.
If Presolol tablets are prescribed with diuretics or other antihypertensive agents, an additive effect can be expected. When transferring patients from other treatment regimens, Presolol should be introduced in the manner described, see Section 4.2 Dose and Method of Administration, and the dosage of other treatments should be reduced gradually.

Individual variations.

There is a large variation in hypotensive response between patients and this may be due to variable rate of absorption and first-pass metabolism during the passage of labetalol through the intestinal wall and liver.

Significant cardiomegaly.


Use in renal impairment.

Labetalol does not adversely affect renal function and is a particularly suitable drug for use in hypertensive patients with renal disease (see Section 5.2 Pharmacokinetic Properties, Pharmacokinetics in special populations). In patients with severe renal disease, haemodynamic changes following beta-blockade may impair renal function further.

Use in the elderly.

The bioavailability and half-life of labetalol hydrochloride are increased in the elderly. In addition, the hypotensive response is greater in this age group following administration. Therefore, lower doses of Presolol are likely to be required in elderly patients.

Paediatric use.

There is little reported clinical experience of the use of labetalol in children. Thus, care should be taken in establishing individual dosage requirements in children. Safety and effectiveness in children have not been established.

Effects on laboratory tests.

Labetalol fluoresces in alkaline solution at an excitation wavelength of 334 nanometre and a fluorescence wavelength of 412 nanometre and may, therefore, interfere with the assays of certain fluorescent substances including catecholamines.
The presence of labetalol metabolites in the urine may result in falsely elevated levels of urinary catecholamines, metanephrine, normetanephrine, and vanillylmandelic acid (VMA) when measured by fluorimetric or photometric methods. In screening patients suspected of having a phaeochromocytoma and being treated with labetalol hydrochloride, a specific method, such as high performance liquid chromatographic assay with solid phase extraction, should be employed in determining levels of catecholamines.
Labetalol may produce a false positive result when urine is screened for amphetamines. Care must be taken to corroborate any such result with a more specific method.
Labetalol has been shown to reduce the uptake of radioisotopes of metaiodobenzylguanidine (MIBG). Care should therefore be taken in interpreting results from MIBG scintigraphy.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Postural hypotension may be enhanced by the concurrent administration of other vasodilators.
The interaction of labetalol with methyldopa and with clonidine has been examined on blood pressure and heart rate in animals. The results indicate that labetalol, given together with methyldopa or clonidine, should exert an additional hypotensive effect in human beings who are sensitive to both drugs in the combined therapy.
Concomitant use of tricyclic antidepressants may increase the incidence of tremor.
Cimetidine increases the oral bioavailability of labetalol. Care is required in determining the dose of labetalol in patients who are also taking cimetidine.
Concurrent administration of some NSAIDs may impair the antihypertensive effects of labetalol, possibly due to their inhibition of renal synthesis of vasodilatory prostaglandins. Dosage adjustment may be necessary.
See Section 4.4 Special Warnings and Precautions for Use.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
Beta-adrenergic blocking agents may cause bradycardia in the fetus and newborn infant. During the final part of pregnancy and parturition these drugs should therefore only be given after weighing the needs of the mother against the risk to the foetus.
Labetalol is known to cross the placental barrier and has been found to bind to the eyes of fetal animals. Labetalol has been used successfully in the treatment of hypertension arising in the second and third trimester of pregnancy. Labetalol crosses the placental barrier and the possibility of the consequences of alpha- and beta-adrenoreceptor blockade in the fetus and neonate should be borne in mind.
Perinatal and neonatal distress (bradycardia, hypotension, respiratory depression, hypoglycaemia, hypothermia) has been rarely reported. Sometimes these symptoms developed a day or two after birth. Response to supportive measures (e.g. intravenous fluids and glucose) is usually prompt but with severe pre-eclampsia, particularly after prolonged intravenous labetalol, recovery may be slower. This may be related to diminished hepatic metabolism in premature babies. Intrauterine and neonatal deaths have been reported but other drugs (e.g. vasodilators, respiratory depressants) and the effects of pre-eclampsia, intrauterine growth retardation and prematurity were implicated. Such clinical experience warns against unduly prolonging high dose labetalol and delaying delivery and against coadministration of hydralazine.
Administration of labetalol in the first trimester of pregnancy is not recommended. Labetalol does not appear to be teratogenic in rats or rabbits, but it is embryolethal when given in a dose of 50 mg/kg orally.
Labetalol is excreted in breast milk. No adverse reactions in breastfeeding infants have been reported. It is not recommended for nursing mothers unless the expected benefits outweigh any potential risks.

4.8 Adverse Effects (Undesirable Effects)

Labetalol is normally well tolerated. Symptoms of postural hypotension may occur if the initial dosage is too high or if the dose is increased too rapidly.

Cardiovascular disorders.

Postural hypotension may occur if the initial dosage is too high or if the dose is increased too rapidly. Occasionally bradycardia and heart block have been reported.

Central and peripheral nervous system.

Transient dizziness, headache, tiredness, depressed mood and lethargy may occur. There have been reports of a tingling sensation of the skin (especially of the scalp) associated with labetalol treatment usually occurring early in treatment and which is transient in nature.

Collagen disorders.

There have been occasional reports of positive antinuclear antibodies unassociated with disease as well as the occasional case of systemic lupus erythematosus and very occasionally drug fever.

Ocular disorders.

Blurred vision, eye irritation and dry eyes have been reported.

Hepatic disorders.

Reports of raised liver function tests; jaundice (both hepatocellular and cholestatic) and hepatitis have on occasion been reported, the signs and symptoms of which are usually reversible on withdrawal of the drug. Hepatic necrosis has been reported (see Section 4.4 Special Warnings and Precautions for Use).

Musculoskeletal disorders.

There has been one report of toxic myopathy. Tremor has been reported in the treatment of hypertension of pregnancy. Muscle cramps have been reported.

Respiratory disorders.

Bronchospasm may occur in susceptible individuals.

Skin and appendages.

Rashes of various types such as generalised maculopapular, lichenoid, urticarial, bullous, lichen planus, psoriasiform and facial erythema, Peyronie's disease and reversible alopecia.

Genitourinary disorders.

Acute retention of urine and difficulty in micturition have occurred during labetalol treatment.

Gastrointestinal disorders.

Epigastric pain, nausea and vomiting.

Hypersensitivity.

Rash, pruritus, angioedema and dyspnoea.

Others.

Ankle swelling; failure of ejaculation; nasal congestion and sweating.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Presolol tablets are to be taken orally, preferably after meals.
For all patients, the dosage of Presolol must be titrated against blood pressure response.
The recommended starting dose for all patients is 100 mg to 200 mg twice daily. The dosage should then be increased at weekly intervals until satisfactory control of blood pressure is attained. It is important to follow these dosage instructions and to increase the dosage gradually, in order to minimise side effects.
Effective daily doses vary between 200 mg and 2.4 g. In those patients on high doses, a regimen of three to four doses a day may be necessary.
Hypertension may be controlled by Presolol alone. If Presolol tablets are prescribed with diuretics, or other antihypertensive agents, an additive effect can be expected.
When transferring patients from other treatment regimens, Presolol should be introduced in the manner described above and the dosage of other treatments should be reduced gradually.

4.7 Effects on Ability to Drive and Use Machines

Labetalol hydrochloride may cause occasional dizziness or fatigue. Patients should therefore be warned of the possibility of impairment of the ability to drive or operate machinery.

4.9 Overdose

Overdosage with labetalol causes excessive hypotension which is posture sensitive and, sometimes, excessive bradycardia. Patients should be laid supine and, if necessary, their legs should be raised to improve the blood supply to the brain. Atropine 3 mg intravenously should be given to relieve the bradycardia. Gastric lavage or induced emesis is recommended if the overdosage is recent (2 to 3 hours). Oliguric renal failure has been reported after massive overdosage of labetalol hydrochloride tablets.
If further measures are required to obtain adequate circulatory function, intravenous noradrenaline may be preferable to isoprenaline, the established pharmacological treatment for excessive cardiac beta-blockade. The recommended starting dose of noradrenaline in patients is 5 to 10 microgram by intravenous injection, repeated as required, according to the response. Alternatively, noradrenaline may be infused at a rate of 5 microgram/minute until a satisfactory response is achieved.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

The tablets contain the following excipients: microcrystalline cellulose, magnesium stearate, colloidal anhydrous silica, silicon dioxide, sodium starch glycollate, pregelatinised maize starch, sucrose and Opadry Orange OY-LS-23015.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C.

6.5 Nature and Contents of Container

Container type: bottle (HDPE).
Pack sizes: 100.
Some strengths, pack sizes and/or pack types may not be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking it to your local pharmacy.

Summary Table of Changes