Consumer medicine information

Deralin

Propranolol hydrochloride

BRAND INFORMATION

Brand name

Deralin

Active ingredient

Propranolol hydrochloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Deralin.

What is in this leaflet

This leaflet answers some common questions about Deralin.

It does not contain all of the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor has weighed the risks of you taking Deralin against the benefits expected 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 Deralin is used for

Deralin works by affecting the body's response to some nerve impulses, especially in the heart.

As a result, it decreases the heart's need for blood and oxygen and therefore reduces the amount of work the heart has to do. It also widens the blood vessels in the body, as well as helping the heart to beat more regularly.

Deralin contains the active ingredient propranolol hydrochloride, which belongs to a group of medicines called beta-blockers.

Deralin is used to treat or prevent a number of conditions. These include:

  • hypertension (high blood pressure)
  • angina
  • heart beat or heart rhythm irregularities, including those caused by anxiety or an overactive thyroid gland
  • essential tremor (shaking of head, chin, hands)
  • phaeochromocytoma, a rare tumour of the adrenal gland
    (only when used in combination with another medicine)
  • heart attack prevention or treatment, or to reduce the risk of heart problems after a heart attack
  • Fallot's Tetralogy
  • migraine headache prevention.

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

Deralin is available only with a doctor's prescription.

Before you take Deralin

When you must not take it

Do not take Deralin if you are allergic to:

  • propranolol hydrochloride
  • any of the ingredients listed at the end of this leaflet
  • any other similar medicines such as beta-blockers

Some of the symptoms of an allergic reaction may include skin rash, itching or hives; swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing; wheezing or shortness of breath.

Do not take Deralin if you have asthma or severe breathing problems. Taking Deralin may make these conditions worse.

Do not take Deralin if you have certain other heart problems for example heart failure, low blood pressure, problems with your circulation, Prinzmetal's angina or a slow heartbeat. Taking Deralin may make these conditions worse.

Do not take Deralin if you have low blood sugar levels. Taking Deralin may make these conditions worse.

Do not take Deralin if you are receiving:

  • emergency treatment for shock or severely low blood pressure
  • certain anaesthetics for medical or dental procedures.

Do not take Deralin if the expiry date (EXP) printed on the pack has passed. If you take this medicine after the expiry date, it may not work as well.

Do not take Deralin if the packaging shows signs of tampering or the tablets do not look quite right.

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 are allergic to any other medicines, foods, dyes or preservatives.

Tell your doctor if you are pregnant or plan to become pregnant. Deralin should not be taken during pregnancy unless advised by your doctor. This medicine like other medicines in its group has been associated with unwanted effects in the unborn or newborn baby.

Tell your doctor if you are breastfeeding or wish to breastfeed. Like other beta-blocker medicines, Deralin passes into breast milk and is not recommended for use during breastfeeding.

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

  • asthma or serious breathing problems
  • heart problems including angina
  • low blood pressure
  • an overactive thyroid gland
  • diabetes or a history of low blood sugar
  • kidney problems
  • liver problems
  • any medical condition affecting your blood vessels or circulation.

Your doctor may want to take special care if you have any of these conditions.

Tell your doctor if you are fasting or have been fasting recently.

Tell your doctor if you plan to have surgery, including dental surgery, especially if it requires a general anaesthetic.

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

Taking other medicines

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

Some medicines may be affected by Deralin, or may affect how well it works. These include:

  • calcium channel blockers, medicines used to treat high blood pressure, angina and other heart conditions such as verapamil, diltiazem, nifedipine
  • digoxin, a medicine used to treat heart failure
  • medicines for migraines such as ergotamine, dihydroergotamine, rizatriptan
  • medicines used to treat diabetes including insulin
  • medicines used to treat arthritis, pain or inflammation such as ibuprofen or indometacin
  • warfarin, a medicine used to prevent blood clots
  • cimetidine, a medicine used to treat reflux and stomach ulcers
  • theophylline, a medicine used to treat asthma
  • chlorpromazine and thioridazine, medicines used to treat psychiatric disorders
  • rifampicin, an antibiotic used to treat tuberculosis
  • adrenaline (epinephrine), a medicine used in emergency situations.

Your doctor can tell you what to do if you are taking any of these medicines.

If you are not sure whether you are taking any of these medicines, check with your doctor or pharmacist. Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking Deralin.

How to take Deralin

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.

How much to take

For high blood pressure
The usual starting dose is one 40mg tablet taken twice a day for one week.

The dose is then usually increased to between 120mg to 320mg daily.

If you are taking other medicines which lower blood pressure, your doctor may need to change the dose of them to obtain the best results for you.

For angina and tremor
The usual dose is 40mg taken two or three times a day.

To treat or prevent heart attack
The usual dose is 80mg taken twice a day, often starting with 40mg taken four times a day for 2 or 3 days.

For migraine prevention

Adults
The usual dose is 40mg taken twice a day. This may need to be increased up to 80mg twice a day.

Children over 7 years
The starting dose is 10mg taken once or twice daily. This can be increased if necessary.

Other conditions
Your doctor will tell you what dose to take.

Your doctor may tell you to take a different amount of Deralin to the one given in this leaflet.

Follow your doctor's instructions carefully.

How to take Deralin

Swallow the tablets with a glass of water.

When to take Deralin

Deralin can be taken with or without food.

If you forget to take Deralin

If it is almost time for your next dose (within 6 hours), 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 tablets as you would normally.

Do not take a double dose to make up for the dose you missed.

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.

How long to take Deralin for

To properly control your condition, Deralin must be taken every day.

Keep taking Deralin for as long as your doctor recommends. Do not stop taking Deralin, or lower the dose, without checking with your doctor.

If you take too much Deralin (overdose)

Immediately telephone your doctor, or the Poisons Information Centre (telephone 13 11 26), or go to Accident and Emergency at the nearest hospital, if you think you or anyone else may have taken too much Deralin.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If you take too much Deralin, you may feel faint, very tired, have a slow heart beat or have difficulty breathing.

While you are taking Deralin

Things you must do

Before starting any new medicine, tell your doctor or pharmacist that you are taking Deralin.

Tell all the doctors, dentists and pharmacists who are treating you that you are taking Deralin.

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

If you have or have had 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 Deralin may cause allergic reactions to be worse and harder to treat.

If you plan to have surgery (including dental surgery) that requires a general anaesthetic, tell your doctor or dentist that you are taking Deralin. Your blood pressure may drop suddenly if Deralin interacts with the anaesthetic.

If you feel light-headed, dizzy or faint when getting out of bed or standing up, get up slowly. You may feel light-headed or dizzy when you begin to take Deralin.

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 gets worse or continues, talk to your doctor.

Since Deralin is meant to be taken regularly every day, keep a continuous supply of medicine so you don't run out, especially over weekends or on holidays.

If you are being treated for diabetes, make sure you check your blood glucose level regularly and report any changes to your doctor. Deralin may affect how well your diabetes is controlled. Deralin may hide some signs of low blood glucose levels (hypoglycaemia) such as increased heart rate.

It may also prolong the blood glucose lowering effect of your diabetic medicine or increase the time it takes for your body to recover from low blood glucose. Your doctor therefore may need to adjust the dose of your insulin or diabetic medicines.

Non-diabetic patients:
Deralin may also occasionally cause low blood sugar (hypoglycaemia) in non-diabetic patients.

These may include the newly born, toddlers, children, elderly, patients suffering from overdose, patients suffering from chronic liver disease, fasting patients or patients on haemodialysis

Visit your doctor regularly so they can check on your progress.

Things you must not do

Do not stop taking Deralin, or lower the dose, without checking with your doctor. Stopping Deralin suddenly may worsen your angina or cause other heart complications to occur. Your doctor will tell you how to gradually reduce the amount of Deralin you are taking before stopping completely. This may help reduce the possibility of your condition getting worse.

Do not use Deralin to treat any other conditions unless your doctor tells you to.

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

Things to be careful of

Be careful driving or operating machinery until you know how Deralin affects you. Deralin is unlikely to affect your ability to drive or operate machinery. However, as dizziness or fatigue have occasionally occurred in some people, do not drive, operate machinery or do anything else that could be dangerous until you know how Deralin affects you.

Be careful drinking alcohol while taking Deralin. Combining Deralin and alcohol can make you more dizzy or lightheaded. Alcohol can also increase the effects of Deralin.

Make sure you drink enough water in hot weather and during exercise, especially if you sweat a lot. If you do not drink enough water while taking Deralin, you may feel faint, lightheaded or sick. This is because your blood pressure is dropping suddenly. If you continue to feel unwell, tell your doctor.

Dress warmly during cold weather, especially if you will be outside for a long time. Deralin, like other beta-blocker medicines tend to make you more sensitive to cold temperatures, especially if you have circulation problems.

Side effects

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

Deralin helps most people and is usually well tolerated, but it may have unwanted side effects in some 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.

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

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

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

  • tiredness
  • dizziness
  • sleeping problems, nightmares
  • rash, flushing
  • hair loss
  • feeling tired, lethargic, lack of energy
  • feeling sick (nausea), vomiting
  • cold hands or feet
  • diarrhoea
  • flatulence
  • stomach pain
  • loss of appetite.

The above list includes the milder side effects of Deralin.

Tell your doctor immediately if you notice any of the following:

  • dry or irritated eyes, blurred vision, conjunctivitis
  • difficulty hearing
  • unusual bleeding or bruising under the skin
  • changes in mood such as depression, confusion, hallucinations
  • sexual problems
  • trouble passing urine
  • slow heart beats

The above list includes serious side effects which may require medical attention.

Tell your doctor immediately or go to Accident and Emergency at the nearest hospital if you notice any of the following:

  • any type of skin rash
  • swelling of the face, lips, tongue or throat which may cause difficulty in swallowing
  • chest tightness, difficulty breathing, wheezing, asthma attack
  • fast, slow or irregular heart beat
  • shortness of breath (sometimes with tiredness, weakness and reduced ability to exercise), which may occur together with swelling of the feet or legs due to fluid build-up.

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation.

This medicine may cause low blood sugar levels (hypoglycaemia) in some people. This may occur in people being treated with insulin and other medicines for diabetes, but occasionally can also occur in the newly born, infants, children, the elderly, people who are fasting, undergoing haemodialysis, suffering from chronic liver disease or from an overdose.

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

This is not a complete list of all possible side effects.

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

After taking Deralin

Storage

Keep Deralin 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.

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

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

Do not store Deralin or any other medicine in the bathroom or near a sink.

Do not leave Deralin in the car or on window sills. Heat and dampness can destroy some medicines.

Disposal

If your doctor tells you to stop taking Deralin, or your tablets have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

Deralin tablets are available in 3 strengths:

  • Deralin 10 - round red tablet marked "PP/10" on one side and "G" on the other. Each bottle contains 100 tablets.
  • Deralin 40 - round red tablet marked "PP/40" on one side and "G" on the other. Each bottle contains 100 tablets.
  • Deralin 160 - round red tablet marked "PP/160" on one side and "G" on the other. Each bottle contains 50 tablets.

Ingredients

The active ingredient in Deralin is propranolol hydrochloride.

  • Each Deralin 10 tablet contains 10 mg of propranolol hydrochloride.
  • Each Deralin 40 tablet contains 40 mg of propranolol hydrochloride.
  • Each Deralin 160 tablet contains 160 mg of propranolol hydrochloride.

The tablets also contain the following inactive ingredients:

  • calcium carbonate
  • croscarmellose sodium
  • gelatin
  • pregelatinised maize starch
  • magnesium stearate
  • Opadry Red OY-7601.

Deralin tablets contain sulfites. The tablets are gluten free.

Manufacturer

Deralin 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:

Deralin 10 - AUST R 17612

Deralin 40 - AUST R 17614

Deralin 160 - AUST R 17613

This leaflet was prepared on 21 August 2019.

Deralin_cmi\Aug19/00

Published by MIMS October 2019

BRAND INFORMATION

Brand name

Deralin

Active ingredient

Propranolol hydrochloride

Schedule

S4

 

1 Name of Medicine

Propranolol hydrochloride.

6.7 Physicochemical Properties

Propranolol hydrochloride is a white or almost white powder; odourless or almost odourless. Propranolol is soluble in 20 parts of water and in 20 parts of ethanol (96%); slightly soluble in chloroform.
Propranolol is a β-adrenoreceptor blocking agent which is structurally related to other β-blocking agents such as atenolol, pindolol and oxprenolol, differing from these compounds by substitution on the aromatic ring.
Chemical name: (2RS)-1-[(1-methylethyl) amino]-3-(naphthalen-1-yloxy) propan-2-ol hydrochloride.
Molecular formula: C16H21NO2HCl.
Molecular weight: 295.8.

Chemical structure.


CAS number.

318-98-9.

2 Qualitative and Quantitative Composition

Each Deralin tablet contains 10 mg, 40 mg or 160 mg of propranolol hydrochloride as the active ingredient.

Excipients of known effect.

Sulfites.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Deralin 10 tablet: red film coated, marked PP/10 on one side, G on reverse.
Deralin 40 tablet: red film coated, marked PP/40 on one side, G on reverse.
Deralin 160 tablet: red film coated, marked PP/160 on one side, G on reverse.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Propranolol hydrochloride is a β-adrenoreceptor blocking agent which acts nonselectively on β-receptors (β1 and β2). It has little intrinsic sympathomimetic activity. It has some membrane stabilising effect.
Chemically, it is a racemic mixture and the active form is the S(-) isomer of propranolol. The most important effect of propranolol hydrochloride is to reduce the influence of excessive sympathetic nervous stimulation on the heart. Pulse rate, force of cardiac contraction and cardiac output are all reduced, resulting in a significant reduction in myocardial oxygen demand, greater than the reduction in work. These effects, singly or in combination, are of therapeutic value in several cardiovascular diseases.
Propranolol hydrochloride reduces raised blood pressure by an unknown mechanism. The drug also inhibits exercise induced tachycardia and this effect is related to plasma concentration. No correlation has been found between the plasma concentration of propranolol and its antihypertensive effect.
The possible mechanism of the antianginal activity of propranolol hydrochloride appears to be due to a reduction in left ventricular work and oxygen utilisation resulting from inhibition of cardiac sympathetic nerve stimulation. Serotonin antagonism has been demonstrated with propranolol hydrochloride. The therapeutic benefit of this property in centrally mediated disorders is uncertain.
Propranolol hydrochloride, as with other β-adrenoreceptor blocking agents, has negative inotropic effects and is therefore contraindicated in congestive heart failure.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Studies with propranolol hydrochloride in man indicate that it is almost completely absorbed from the intestine. A large part of the absorbed drug is lost to the systemic circulation due to the first-pass metabolism in the liver. After repeated administration, the first pass removal process becomes saturated and, at steady state, the plasma concentration is proportional to the dose, although there is some variation between patients as to the blood levels achieved at a given dose.
In addition, correlation of plasma level to therapeutic effect varies considerably with propranolol as with some other β-blockers. Blood level measurements show that after intravenous administration, the concentration in the circulation decreases rapidly due mainly to uptake by tissues generally.

Bioavailability.

In general, the peak blood level occurs between one and three hours after the dose, and will have an average value of 0.1 microgram/mL per 80 mg single dose. The peak blood level is proportional to the dose. With chronic administration, the mean plasma half-life is from three to six hours, determined by clearance and plasma binding.

Distribution.

Propranolol is absorbed from the circulation and is widely distributed throughout the body tissues.

Protein binding.

Approximately 93% is plasma bound in humans.

Metabolism.

Propranolol is completely metabolised primarily by the liver. Hydroxylation of the aromatic nucleus occurs with degradation of the isoprenaline side chain. Over 20 metabolites have been identified. One of these, the 4-hydroxy metabolite, found only after oral administration has β-adrenergic blocking properties.

Excretion.

Some 95 to 100% of a dose of propranolol hydrochloride is excreted as metabolites and their conjugates in the urine.

Half-life.

The plasma half-life of oral propranolol is of the order of three to six hours. The pharmacological effect lasts much longer.

Clinical implications of pharmacokinetic data.

Propranolol hydrochloride has a variable bioavailability due to an avid hepatic binding mechanism. This first pass effect varies from individual to individual and will determine the drug plasma concentration. A good estimation of β-blockade and bioavailability can be clinically gauged by checking for reduction in standing or exercise heart rate. This also gives a simple guide to compliance.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

Angina pectoris.
Hypertension.
Prevention of migraine.
Cardiac dysrhythmias: certain intrinsic cardiac dysrhythmias; dysrhythmias associated with thyrotoxicosis; anxiety tachycardia; certain drug induced dysrhythmias (e.g. tachycardia due to digitalis or adrenaline (epinephrine) overdosage).
Essential tremor, including familial and senile tremor.
Phaeochromocytoma (only with concurrent α-receptor blockade).
Hypertrophic subaortic stenosis.
Suspected or definite myocardial infarction.
Fallot's tetralogy.

4.3 Contraindications

Cardiovascular.

Congestive heart failure.
Right ventricular failure secondary to pulmonary hypertension.
Significant right ventricular hypertrophy.
Sick sinus syndrome.
Sinus bradycardia (less than 45 to 50 beats/ minute).
Second and third degree A-V block.
Hypotension.
Severe peripheral arterial circulatory disturbances.
Prinzmetal angina.

Hypoglycaemia, prolonged fasting and metabolic acidosis.

Propranolol must not be used in patients prone to hypoglycaemia, i.e. patients after prolonged fasting or patients with restricted counter regulatory reserves (see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)).
In metabolic acidosis (e.g. in diabetes), the premonitory signs of hypoglycaemia may be masked in patients receiving hypoglycaemic agents.

Asthma/ bronchospasm.

β-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, β-blockers are contraindicated in any patient with a history of bronchial asthma, airways obstruction or a tendency to bronchospasm. Use of cardioselective β-blockers can also result in severe bronchospasm. If such therapy must be used, great caution should be exercised. Alternative therapy should be considered.

Other.

Allergic disorders (including allergic rhinitis) which may suggest a predisposition to asthma or bronchospasm.
Shock (including cardiogenic and hypovolaemic shock).
Hypersensitivity to the drug.
Anaesthesia with agents that produce myocardial depression (e.g. ether, chloroform).
Untreated phaeochromocytoma.

4.4 Special Warnings and Precautions for Use

Asthma/ bronchospasm.

β-Adrenergic blockade of the smooth muscle of bronchi and bronchioles results in an increased airways resistance. This may be dangerous in susceptible patients and associated sometimes with a fatal outcome (see Section 4.3 Contraindications.)

Cardiac failure.

β-Blockade depresses myocardial contractility and may precipitate cardiac failure in some patients with a history of cardiac failure, chronic myocardial insufficiency or unsuspected cardiomyopathy as may occur in chronic alcoholism. In patients without a history of cardiac failure, continuing depression of the myocardium may lead to cardiac failure. If signs of cardiac failure present, the patients should be fully digitalised and/or given an ACE inhibitor or vasodilators with or without a diuretic and carefully monitored. If cardiac failure persists, Deralin should be withdrawn (see Section 4.4 Special Warnings and Precautions for Use, Abrupt withdrawal of therapy).

Note.

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

Abrupt withdrawal of therapy.

Care should be taken if β-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 β-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, β-blockers should not be withdrawn, unless indicated.
Patients with angina should be warned against abrupt withdrawal of the drug and the need to ensure that supplies do not run out.

Concomitant therapy with calcium antagonists.

The concomitant use of β-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, particularly in patients with impaired ventricular function and/or sinoatrial or atrioventricular conduction abnormalities. 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 β-blockers. If excessive hypotension develops, the calcium antagonist should be stopped or the dosage reduced.

First degree heart block.

Due to its negative effect on conduction time, caution must be exercised if Deralin is given to patients with first degree heart block.

Peripheral circulation.

β-Blockade may impair the peripheral circulation and exacerbate the symptoms of peripheral vascular disease.

Heart rate.

One of the pharmacological actions of β-adrenoreceptor blocking medicines is to reduce heart rate. In the rare instance when symptoms may be attributable to the slow heart rate, the dosage may be reduced.

Antiarrhythmic drugs.

Care should be taken when prescribing β-blockers with antiarrhythmic drugs. Interactions have been reported during concomitant β-blocker therapy with the class IA agents disopyramide, and less frequently quinidine; class IB agents, mexiletine and lidocaine (lignocaine); class IC agent, flecainide; the class III agent, amiodarone; and the class IV antiarrhythmic agents.

Prinzmetal angina.

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

Euthyroid hyperthyroxinaemia.

The effects of β-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.

History of anaphylactic reaction.

While taking β-blockers, patients with a history of anaphylactic reaction to a variety of allergens may have a more severe reaction on repeated challenge. Such patients may be unresponsive to the usual doses of adrenaline (epinephrine) used to treat the allergic reaction.

Lidocaine (lignocaine).

Administration of propranolol during infusion of lidocaine (lignocaine) may increase the plasma concentration of lidocaine (lignocaine)by about 30%. Patients already receiving propranolol tend to have higher lidocaine (lignocaine)levels than controls. The combination should be avoided.

Hypoglycaemia.

Propranolol may block/ modify the signs and symptoms of hypoglycaemia (especially tachycardia). Propranolol occasionally causes hypoglycaemia, even in nondiabetic patients, e.g. neonates, infants, children, elderly patients, patients on haemodialysis or patients suffering from chronic liver disease and patient suffering from overdose. Severe hypoglycaemia associated with propranolol has rarely presented with seizures and/or coma in isolated patients. Caution must be exercised in the concurrent use of Deralin and hypoglycaemic therapy in diabetic patients (see Section 4.4 Special Warnings and Precautions for Use, Diabetes; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy). Propranolol may prolong the hypoglycaemic response to insulin.

Anaesthesia and the perioperative period.

β-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 β-blockade be continued perioperatively. The anaesthetist must be made aware of β-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 well tolerated, although older agents (ether, methoxyflurane) were sometimes associated with severe circulatory depression in the presence of β-blockade.

Diabetes.

β-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, β-blockade may result in the loss of diabetic control and delayed recovery from hypoglycaemia (see Section 4.4 Special Warnings and Precautions for Use, Hypoglycaemia; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). The dose of insulin or oral hypoglycaemic agent may need adjustment.

Other metabolic effects.

β-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 guanethidine requires careful monitoring since the added effect of β-blockade may produce an excessive reduction of the resting sympathetic nervous tone.

Clonidine.

Concurrent use of β-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 β-blocker. If replacing clonidine by β-blocker therapy, the introduction of β-blockers should be delayed for several days after clonidine administration has stopped.

Phaeochromocytoma.

In patients with this condition, an α-blocking drug (e.g. phentolamine/ phenoxybenzamine) should be administered before the β-blocker to avoid exacerbation of hypertension.

Eye and skin reactions.

Various skin rashes and conjunctival xerosis have been reported with β-blockers. Cross reactions may occur between β-blockers, therefore substitutions within the group may not necessarily preclude occurrence of symptoms.
During the long-term treatment with the β-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, serous otitis media, sclerosing peritonitis, pericarditis and pleurisy have been reported. Although the practolol syndrome has not been observed in patients taking other β-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 β-blockers has been suggested but is not proven.

Allergic conditions.

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

Hyperthyroidism.

Because β-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 β-blockers.

Use in hepatic impairment.

Since the half-life may be increased in patients with significant hepatic impairment, care should be taken when starting treatment and selecting the initial dose.

Decompensated cirrhosis.

Propranolol hydrochloride should be used with caution in decompensated cirrhosis.

Portal hypertension.

In patients with portal hypertension, liver function will deteriorate and hepatic encephalopathy may develop. Propranolol may increase the risk if hepatic encephalopathy.

Use in renal impairment.

Since the half-life may be increased in patients with significant renal impairment, caution must be exercised when starting treatment and selecting the initial dose. In patients with severe renal disease, haemodynamic changes following β-blockade may impair renal function further. β-blockers which are excreted mainly by the kidney may require dose adjustment in patients with renal failure.

Use in the elderly.

See Section 4.2 Dose and Method of Administration.

Paediatric use.

No data available.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Digitalis glycosides.

Digitalis glycosides, in association with β-blockers, may increase atrioventricular conduction time.

Sympathomimetic agents.

Concomitant use of sympathomimetic agents e.g. adrenaline (epinephrine), may counteract the effects of β-blockers. Caution must be exercised in the parenteral administration of preparations containing adrenaline (epinephrine) to patients taking β-adrenoreceptor blocking drugs as, in rare cases, vasoconstriction, hypertension and bradycardia may result.

Hypoglycaemics.

Propranolol modifies the tachycardia of hypoglycaemia. Caution should be exercised in the concurrent use of propranolol and hypoglycaemic therapy in diabetic patients. Deralin may prolong the hypoglycaemic response to insulin (see Section 4.4 Special Warnings and Precautions for Use).

Rizatriptan.

Simultaneous administration of rizatriptan and propranolol can cause an increase in rizatriptan plasma concentrations. The increased rizatriptan exposure is presumed to be caused by inhibition of first passage metabolism of rizatriptan through inhibition of monoamine oxidase A. If both drugs are to be used, a rizatriptan dose of 5 mg has been recommended.

Cimetidine, hydralazine and alcohol.

Concomitant use of cimetidine or hydralazine will increase plasma levels of propranolol and concomitant use of alcohol may also increase the plasma levels of propranolol.

Ergot alkaloids.

Care should be taken when using propranolol with ergotamine, dihydroergotamine, or related compounds, since vasospastic reactions have been reported in a few patients.

Prostaglandin synthetase inhibiting drugs.

Concomitant use of prostaglandin synthetase inhibiting drugs, e.g. ibuprofen and indomethacin, may decrease the hypotensive effects of β-blockers.

Chlorpromazine.

Concomitant administration of propranolol and chlorpromazine may result in an increase in plasma levels of both drugs. This may lead to an enhanced antipsychotic effect for chlorpromazine and an increased antihypertensive effect for propranolol.

Other.

Pharmacokinetic studies have shown that the following agents may interact with propranolol due to effects on enzyme systems in the liver which metabolise propranolol and these agents: quinidine, rifampicin, theophylline, warfarin, thioridazine and dihydropyridine calcium channel blockers such as nifedipine, nisoldipine and isradipine. Owing to the fact that blood concentrations of either agent may be affected, dosage adjustments may be needed according to clinical judgment. See Section 4.4 Special Warnings and Precautions for Use above concerning the concomitant therapy with dihydropyridine calcium antagonists.
See Section 4.4 Special Warnings and Precautions for Use for calcium antagonists, antiarrhythmic drugs, lidocaine (lignocaine), anaesthesia and the perioperative period, catecholamine depleting agents and clonidine.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
Deralin should not be given during pregnancy unless its use is essential. β-Blockers reduce placental perfusion, which may result in intrauterine foetal death, immature and premature deliveries.
Perinatal complications, such as a small placenta and intrauterine growth retardation, have been reported in a few cases where the mother took propranolol hydrochloride during pregnancy. Some infants born to mothers treated with propranolol hydrochloride were reported to have hypoglycaemia and/or bradycardia. There is an increased risk of cardiac and pulmonary complications in the neonate in the postnatal period.
There is no evidence of teratogenicity with propranolol hydrochloride.
β-Adrenergic blocking agents may cause pharmacological effects such as bradycardia in the foetus 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.
Most β-blockers, particularly lipophilic compounds, will pass into breast milk although to a variable extent. Breastfeeding is therefore not recommended following administration of these compounds.

4.8 Adverse Effects (Undesirable Effects)

Propranolol hydrochloride is usually well tolerated and side effects are transient in nature, rarely necessitating withdrawal of treatment. The most serious adverse reactions encountered are congestive heart failure and bronchospasm in susceptible patients (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use).
Common adverse reactions include fatigue and/or lassitude (often transient), bradycardia, cold extremities and exacerbation of Raynaud's phenomenon, sleep disturbances including vivid dreams/ nightmares. Other less frequently reported adverse reactions are: gastrointestinal disturbances (anorexia, nausea, vomiting, diarrhoea, abdominal pain); congestive heart failure; dizziness; bronchospasm. Rare cases of thrombocytopenia and purpura have been reported. Bradycardia and CNS symptoms (including mood changes and hallucinations) have been reported rarely.
Reported adverse reactions according to organ systems are recorded below.

Cardiovascular.

Occasionally, a patient may react to small doses and bradycardia and hypotension may develop with subjective dizziness or weakness. In such patients, treatment should be discontinued. These cases are uncommon, but when they do occur, it may be advisable to regard such hypersensitivity as idiosyncratic and to try some other form of treatment. Alternatively the drug may be reintroduced at a lower dosage level and the dose increased more slowly.
Propranolol hydrochloride may exacerbate intermittent claudication in patients with peripheral vascular disease. There have also been some reports of paraesthesia of the hands or of coldness of the extremities in patients showing no signs of vascular disease.
Other cardiovascular adverse reactions reported include congestive heart failure, deterioration of previously controlled heart failure and intensification of A-V block. Propranolol hydrochloride may rarely cause heart block in susceptible patients. Rare cases of postural hypotension which may be associated with syncope have been reported.

Gastrointestinal.

Gastrointestinal disturbances, such as nausea, vomiting, flatulence and diarrhoea have been observed in some patients.

Endocrine.

Hypoglycaemia in neonates, infants, children, elderly patients, patients on haemodialysis, patients on concomitant antidiabetic therapy, patients with prolonged fasting and patients with chronic liver have been reported (see Section 4.3 Contraindications; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).
Isolated reports of impotence have been recorded.

Central nervous system.

Lassitude, "muzziness", insomnia and visual disturbances have been reported in about 2% of patients but these complaints have been mild and are generally avoided by the gradual introduction of the drug.
More serious side effects include severe nightmares and hallucinations. Psychiatric complications (depression, psychoses, psychotic reactions and acute confusional states) may occasionally occur but are unlikely to be severe. It would, however, be wise to restrict treatment in patients who have suffered previous depressive illness.

Respiratory.

Asthma/ bronchospasm, laryngospasm and respiratory distress (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use).

Skin and eyes.

Isolated reports of purpura or erythematous rash have been received. Psoriasiform skin reactions and exacerbation of psoriasis have also been reported. Various other skin rashes and conjunctival xerosis have been reported with β-blocking agents, including propranolol hydrochloride. Such reactions may occur between β-blockers and substitution within the group may not necessarily preclude recurrence of symptoms.

Haematopoietic.

Reduction of platelet adhesiveness; thrombocytopenic purpura; nonthrombocytopenic purpura; agranulocytosis; eosinophilia. An increase in ANA (antinuclear antibodies) has been observed, however, the clinical relevance of this is not clear.

Miscellaneous.

Reduction or loss of libido; alopecia; rarely diminution and loss of hearing; tinnitus; visual disturbances; diminished vision; conjunctivitis; dry eyes; pharyngitis; fever combined with aching and sore throat; urinary retention associated with repeated bouts of paroxysmal tachycardia; flushing of the face. Isolated reports of myasthenia gravis-like syndrome or exacerbation of myasthenia gravis have been reported.
Discontinuance of Deralin should be considered if, according to clinical judgment, the wellbeing of the patient is adversely affected by any of the above reactions. Cessation of therapy with a β-blocker should be gradual. In the rare event of intolerance, manifested as bradycardia and hypotension, the β-blocker should be withdrawn and, if necessary, treatment for overdosage instituted.

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

Note.

Deralin tablets may be taken before or after food.

Adults.

Hypertension.

The standard starting dose is 40 mg twice daily, increasing by the same amount at weekly intervals according to patient response. An adequate response is usually seen in the range 120 to 320 mg/day. Although higher doses may be required, and have been used, the value and safety of doses exceeding 320 mg/day have not been established.

Angina pectoris and essential tremor.

40 mg two or three times daily, increasing by the same amount at weekly intervals according to patient response. An adequate response in essential tremor is usually seen in the range 80 to 160 mg/day and in angina 120 to 320 mg/day.

Migraine.

The standard starting dose is 40 mg twice daily. If a response occurs, this is usually in the range of 80 to 160 mg/day and should be evident within three months.

Note.

In the treatment of migraine, if the attack frequency is reduced significantly, consideration may be given to gradually ceasing therapy as remission may be sustained in a proportion of patients.

Cardiac dysrhythmias, anxiety tachycardia, dysrhythmias associated with thyrotoxicosis and hypertrophic subaortic stenosis.

Most patients respond within the dosage range of 10 to 40 mg three or four times a day.

Phaeochromocytoma.

The patient must always receive concurrent α-receptor blockade.
Preoperative: 60 mg daily in divided doses for three days.
Maintenance: 30 mg daily in divided doses.

Myocardial infarction.

Treatment should start with 40 mg four times a day for two or three days. In order to improve compliance, the total daily dosage may then be given as 80 mg twice a day.

Children.

The dose of Deralin should always be determined according to the cardiac status of the patient and the circumstances necessitating treatment. The doses given below are intended only as a guide.

Cardiac dysrhythmias, phaeochromocytoma, thyrotoxicosis.

0.25 to 0.5 mg/kg three or four times daily as required.

Fallot's tetralogy.

The value of propranolol in this condition is confined mainly to the relief of right ventricular outflow tract shutdown. It is also useful for treatment of associated dysrhythmias and angina. Dosage should be individually determined according to circumstances and the following is only a guide: up to 1 mg/kg repeated three or four times daily as required.

Migraine.

Commence with 10 mg once or twice daily and increase as required up to 2 mg/kg bodyweight per day in divided doses. If a response is to occur, it should be evident in three months. There is no experience in children under the age of seven years.

Note.

In the treatment of migraine, if the attack frequency is reduced significantly, consideration may be given to gradually ceasing therapy as remission may be sustained in a proportion of patients.

Elderly.

Evidence concerning the relationship between blood levels and age is conflicting. With regard to the elderly, the optimum dose should be individually determined according to clinical response.

4.7 Effects on Ability to Drive and Use Machines

Use is unlikely to adversely affect the ability of patients to drive or operate machinery. When driving vehicles or operating machinery, it should be taken into account that occasionally dizziness or fatigue may occur.

4.9 Overdose

Symptoms.

The common signs to be expected in overdosage are bradycardia, hypotension, bronchospasm or acute cardiac failure.

Treatment.

If overdosage occurs, in all cases therapy with propranolol hydrochloride should be discontinued and the patient observed closely. In addition, the following therapeutic measures are suggested.
General treatment should include close supervision in a monitored environment (which may include treatment in an intensive care ward), the use of gastric lavage, activated charcoal and a laxative to prevent absorption of any drug still present in the gastrointestinal tract, the use of intravenous fluids to treat hypotension and shock.

(Note.

Activated charcoal may reduce absorption of the drug if given within one or two hours after ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube, once the airway is protected.)

Bradycardia.

Excessive bradycardia can be countered with atropine 1 to 2 mg intravenously (incrementally in 0.6 mg doses) and/or a cardiac pacemaker. If necessary, this may be followed by a bolus dose of glucagon 10 mg intravenously. If required, this may be repeated or followed by an intravenous infusion of glucagon (1 to 10 mg/hour) depending on response. If no response to glucagon occurs or if glucagon is unavailable, a β-adrenoreceptor stimulant such as isoprenaline (25 micrograms initially) or orciprenaline (0.5 mg), may be given by slow intravenous injection.

Cardiac failure.

Digitalisation and diuretics.

Hypotension.

Vasopressors, e.g. noradrenaline (norepinephrine) or adrenaline (epinephrine) (there is evidence that adrenaline (epinephrine) is the drug of choice).

Bronchospasm.

Administer isoprenaline and aminophylline.
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 inactive ingredients: calcium carbonate, croscarmellose sodium, gelatin, magnesium stearate, Opadry Red OY-7601 (Proprietary Ingredient Number: 1349) and pregelatinized maize starch.

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: 30 (40 mg), 50 (160 mg), 90, 100 (10 mg and 40 mg) and 500 (10 mg and 40 mg) film coated tablets.
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