Consumer medicine information

Minax

Metoprolol tartrate

BRAND INFORMATION

Brand name

Minax

Active ingredient

Metoprolol tartrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Minax.

What is in this leaflet

This leaflet answers some common questions about MINAX. 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 MINAX 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 MINAX is used for

MINAX belongs to a group of medicines called beta-blockers. MINAX is used to:

  • lower high blood pressure, also called hypertension
  • prevent angina (chest pain)
  • treat or prevent heart attacks, or reduce your risk of heart complications following a heart attack
  • prevent migraine headaches.

It works by changing 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.

Your doctor will have explained why you are being treated with MINAX and told you what dose to take. MINAX may be used either alone or in combination with other medicines to treat your condition.

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

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

MINAX is not addictive.

Before you take MINAX

When you must not take it

Do not take MINAX if:

  • You have any allergies to metoprolol tartrate, the active ingredient in MINAX, or any of the ingredients listed at the end of this leaflet, or any other beta-blocker medicine.
    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 or you may feel faint.
  • You have asthma, wheezing, difficulty breathing or other lung problems, or have had them in the past
  • You have a history of allergic problems, including hayfever
  • You have low blood pressure
  • You have a very slow heartbeat (less than 45-50 beats/minute)
  • You have certain other heart conditions
  • You have phaeochromocytoma (a rare tumour of the adrenal gland) which is not being treated already with other medicines
  • You have a severe blood vessel disorder causing poor circulation in the arms and legs
  • You are receiving/having emergency treatment for shock or severely low blood pressure.

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

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.

Do not give MINAX to children. The safety and effectiveness of MINAX in children has not been established.

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

Before you start to take it

You must tell you doctor if you have any allergies to:

  • Metoprolol tartrate or any of the ingredients listed at the end of this leaflet.
  • Any other medicine, including other beta-blocker medicines
  • Any other substances, such as foods, preservatives or dyes.

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

  • Asthma, wheezing, difficulty breathing or other lung problems
  • Diabetes
  • An overactive thyroid gland
  • Liver problems
  • Kidney problems
  • Certain types of angina
  • Any other heart problems
  • Phaeochromocytoma, a rare tumour of the adrenal gland
  • Any blood vessel disorder causing poor circulation in the arms and legs.

Tell your doctor if you are pregnant or plan to become pregnant. Like most beta-blocker medicines, MINAX is not recommended for use during pregnancy.

Tell your doctor if you are breastfeeding or wish to breastfeed. MINAX passes into breast milk, hence there is a possibility that the breastfed baby may be affected.

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

Taking other medicines

Tell your doctor or pharmacist 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 and MINAX may interfere with each other. These include:

  • other beta-blocker medicines, including beta-blocker eye drops
  • calcium channel blockers or calcium antagonists, medicines used to treat blood pressure and angina, for example verapamil and diltiazem
  • medicines used to treat high blood pressure, for example clonidine, hydralazine, and prazosin
  • medicines used to treat abnormal or irregular heartbeat, for example amiodarone, disopyramide and quinidine
  • medicines used to treat arthritis, pain, or inflammation, for example indometacin and ibuprofen
  • warfarin, a medicine used to prevent blood clots
  • digoxin, a medicine used to treat heart failure
  • medicines used to treat diabetes
  • cimetidine, a medicine used to treat stomach ulcers
  • medicines used to treat bacterial infections, for example rifampicin
  • medicines used to treat depression.
  • Monoamine-oxidase inhibitors (MAOIs).

These medicines may be affected by MINAX or may affect how well it works. You may need different amounts of your medicine, or you may need to take different medicines. Your doctor will advise you.

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

If you have not told your doctor about any of these things, tell them before you take any MINAX.

How to take MINAX

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

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

How much to take

For high blood pressure:
The usual starting dose is one 50 mg or 100 mg tablet once a day for one week.

The dose is then usually increased to 50 mg or 100 mg once or twice daily.

Your doctor may tell you to take a different amount of MINAX.

Follow your doctor's instructions carefully.

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

For angina pectoris:
The usual dose is 50 mg or 100 mg taken two or three times a day.

After myocardial infarction (heart attack):
The usual dose is 100 mg taken twice a day, often starting with a lower dose for 2 days.

For migraine prevention:
The usual dose is 50 mg to 75 mg taken twice a day (100 to 150 mg a day), taken in divided doses morning and evening.

Ask your doctor or pharmacist if you are unsure of the correct dose for you. They will tell you exactly how much to take.

How to take it

Swallow the tablets with a glass of water.

MINAX tablets can be divided in half along the breakline, if your doctor has prescribed half a tablet.

When to take it

Take your medicine at about the same time each day before or after food. 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.

DO NOT STOP TAKING MINAX TABLETS SUDDENLY.

The dose needs to be reduced slowly over 7 to 14 days to make sure that your condition does not get worse. Your doctor will tell you how to gradually reduce the dose before stopping completely.

If you forget to take it

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.

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 you or anyone else may have taken too much MINAX. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If you take too much MINAX your blood pressure may drop too far. You will feel faint or faint, and your heart rate will also slow down. You may also have nausea, vomiting and convulsions. In extreme cases, serious heart and lung problems may occur.

While you are taking MINAX

Things you must do

Visit your doctor regularly so they can check on your progress. Elderly patients especially need to be monitored to stop their blood pressure falling too far.

If you become pregnant while taking MINAX, tell your doctor.

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 MINAX may worsen the allergic reactions and cause it to be harder to treat.

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 MINAX. This is because your blood pressure has fallen suddenly.

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.

Make sure you drink enough water during exercise and hot weather when you are taking MINAX, especially if you sweat a lot. If you do not drink enough water while taking MINAX, you may feel faint or light-headed or sick. This is because your blood pressure is dropping too much. If you continue to feel unwell, tell your doctor.

If you are being treated for diabetes, make sure you check your blood sugar level regularly and report any changes to your doctor. MINAX may affect how well your diabetes is controlled. It may also cover up some of the symptoms of low blood sugar (also called hypoglycaemia) such as a fast heartbeat. MINAX may increase the time your body takes to recover from low blood sugar. Your doctor may need to change your dose of diabetic medicines, including insulin.

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

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

Tell your surgeon, anaesthetist or dentist that you are taking MINAX if you plan to have surgery, including dental surgery, that needs a general anaesthetic. MINAX interacts with certain general anaesthetics and may cause a sudden drop in blood pressure.

Tell your doctor if you have to take any medical tests while you are being treated with MINAX.

Things you must not do

Do not stop taking MINAX, or lower the dose, without checking with your doctor. Stopping MINAX suddenly may worsen your angina or cause other heart complications to occur. Your doctor may want you to gradually reduce the amount of MINAX you are taking before stopping completely.

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

Do not give MINAX 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 MINAX affects you. MINAX may cause drowsiness, tiredness, dizziness or lightheadedness in some people. If any of these occur, do not drive, operate machinery or do anything else that could be dangerous.

Be careful drinking alcohol while taking MINAX. Combining MINAX and alcohol can make you more drowsy, dizzy or lightheaded.

Dress warmly during cold weather, especially if you will be outside for a long time. Beta-blocker medicines tend to decrease blood circulation in the skin, fingers and toes. This may make you more sensitive to cold temperatures.

Side effects

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

Like all other medicines, MINAX may have unwanted side effects in some people. 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 this 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 or pharmacist if you notice any of the following and they worry you:

  • headache, tiredness, drowsiness, weakness or lack of energy
  • aches and pains, painful joints
  • feeling sick (nausea), vomiting
  • stomach upset, diarrhoea or constipation, weight gain
  • dry mouth, changes in taste sensation
  • sleeping problems, nightmares
  • mood changes or depression
  • short-term memory loss, inability to concentrate or confusion
  • hair loss
  • increased sweating, runny or blocked nose.

These side effects are usually mild.

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

  • dizziness, lightheadedness or fainting especially on getting up quickly
  • tingling or "pins and needles" in the hands or feet
  • coldness, burning, numbness or pain in the arms and/or legs
  • skin rash or worsening of psoriasis
  • symptoms of sunburn such as redness, itching and blistering, that occur more quickly than usual
  • abnormal thinking or hallucination.
  • buzzing or ringing in the ears, deafness
  • dry or irritated eyes, blurred vision
  • problems with sexual function
  • constant "flu-like" symptoms with tiredness or lack of energy
  • unusual bleeding or bruising

These are serious side effects. You may need urgent medical attention. Serious side effects are rare.

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

  • shortness of breath, being less able to exercise
  • swelling of the ankles, feet or legs
  • chest tightness, difficulty breathing, wheezing, noisy breathing
  • chest pain, changes in heart rate or palpitations
  • swelling of the face, lips, tongue or throat which may cause difficulty swallowing or breathing
  • yellowing of the eyes or skin (jaundice), generally unwell

These are very serious yet rare side effects. You may require immediate medical attention or hospitalisation.

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

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

After taking MINAX

Storage

Keep MINAX 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 a cool dry place where the temperature stays below 30°C.

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

Disposal

If your doctor tells you to stop taking MINAX, 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

MINAX comes in 2 strengths of tablets:

  • MINAX 50 mg - round, white, scored tablet marked ML/50 on one side and a Greek alpha symbol on the reverse. Each bottle contains 100 tablets.
  • MINAX 100 mg - round, white, scored tablet marked ML/100 on one side and Greek alpha symbol on the reverse. Each bottle contains 60 tablets.

Ingredients

The active ingredient in MINAX is metoprolol tartrate:

  • each MINAX 50 mg tablet contains 50 mg of metoprolol tartrate
  • each MINAX 100 mg tablet contains 100 mg of metoprolol tartrate.

The tablets also contain:

  • lactose monohydrate
  • microcrystalline cellulose
  • povidone
  • colloidal anhydrous silica
  • sodium starch glycollate
  • magnesium stearate.

MINAX 100 also contains:

  • purified talc
  • carmellose sodium.

MINAX contains sugars (as lactose), traces of galactose and sulfites.

The tablets are gluten free.

Manufacturer

MINAX is made in Australia by:

Alphapharm Pty Ltd trading as Viatris
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.viatris.com.au
Phone: 1800 274 246

This leaflet was prepared in August 2023.

Australian registration numbers:

MINAX 50 - AUST R 34408

MINAX 100 - AUST R 34410

MINAX is a Viatris company trade mark

MINAX_cmi\Aug23/00

Published by MIMS September 2023

BRAND INFORMATION

Brand name

Minax

Active ingredient

Metoprolol tartrate

Schedule

S4

 

1 Name of Medicine

Metoprolol tartrate.

2 Qualitative and Quantitative Composition

Each Minax 50 tablet contains 50 mg of metoprolol tartrate as the active ingredient.
Each Minax 100 tablet contains 100 mg of metoprolol tartrate as the active ingredient .

Excipients with known effects.

Sugars as lactose and trace quantities of sulfites.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Minax 50.

White, round tablet, marked "ML/50" on one side, "α" on the reverse.

Minax 100.

White, round tablet, marked "ML/100" on one side, "α" on the reverse.

4 Clinical Particulars

4.1 Therapeutic Indications

Hypertension.

As monotherapy or for use in combination with other antihypertensives.

Angina pectoris.

For long-term prophylaxis. Glyceryl trinitrate should be employed if necessary for alleviating acute attacks.
Confirmed or suspected myocardial infarction.
Prevention of migraine.

4.2 Dose and Method of Administration

It is advisable to individualise the dosage.

Hypertension.

Mild.

50 or 100 mg once daily for one week.

Moderate to severe.

50 or 100 mg twice daily for one week.

Maintenance.

50 or 100 mg once or twice daily. Some patients may respond to 50 mg once daily. A larger number will respond to 100 mg once daily as initial and maintenance therapy. Response is rarely improved by increasing the dose beyond 200 mg daily.
The maximum daily dose should not exceed 400 mg. Although twice daily dosage is optimal, in those patients whose maintenance dosage is 150 mg daily or less, it may be administered as a single dose.

Angina pectoris.

50 mg to 100 mg two or three times daily.

Myocardial infarction.

The recommended dosage can be reduced depending on the haemodynamic status of the patient. Initially, therapy should commence with 50 mg twice daily and be continued for 48 hours.

Maintenance.

Generally 100 mg twice daily.

Prevention of migraine.

100 to 150 mg given in divided doses morning and evening.

4.3 Contraindications

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, β-blockers are contraindicated in any patient with a history of 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.
Hypersensitivity to metoprolol tartrate, related derivatives, or any of the excipients in Minax.
Sensitivity to other β-blockers (cross-sensitivity between β-blockers can occur).
Second and third degree atrioventricular block.
Non-compensated congestive heart failure (see Section 4.4 Special Warnings and Precautions for Use).
Sinus bradycardia (less than 45 to 50 beats/minute).
Sick-sinus syndrome (unless a permanent, appropriately functioning pacemaker is in place).
Severe peripheral arterial circulatory disorders.
Shock (including cardiogenic and hypovolaemic shock).
Myocardial infarction patients with a heart rate of < 45 beats/minute, a PR interval of > 0.24 seconds, a systolic blood pressure of < 100 mmHg, and/or moderate to severe non-compensated heart failure.
Right ventricular failure secondary to pulmonary hypertension.
Significant right ventricular hypertrophy.
Hypotension.
Untreated phaeochromocytoma (see Section 4.4 Special Warnings and Precautions for Use).
Allergic disorders (including allergic rhinitis) which may suggest a predisposition to bronchospasm.
Continuous or intermittent inotropic therapy acting through beta-receptor agonism.

4.4 Special Warnings and Precautions for Use

Bronchospastic disease.

In general, patients with bronchospastic disease should not be given β-blockers of any type (e.g. selective or nonselective). If such therapy must be used, great caution should be exercised. Alternative therapy should be considered.

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 signs of cardiac failure are present, the patient should be fully digitalised and/or given a diuretic and carefully monitored. If cardiac failure persists, metoprolol tartrate should be discontinued gradually (see Section 4.4 Special Warnings and Precautions for Use, Abrupt withdrawal).
Beta-blockers should not be used in patients with untreated congestive heart failure. This condition should first be stabilised.

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.

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.

Conduction disorders.

Very rarely, a pre-existing A-V conduction disorder of moderate degree may become aggravated (possibly leading to A-V block). Minax should be administered with caution to patients with first degree A-V block (see Section 4.3 Contraindications).

Phaeochromocytoma.

In patients with phaeochromocytoma, an α-blocker (e.g. phentolamine or phenoxybenzamine) should be administered before the β-blocker to avoid exacerbation of hypertension.

Diabetes.

Minax should be used with caution in patients with diabetes mellitus, especially those who are receiving insulin or oral hypoglycaemic agents. Diabetic patients should be warned that β-blockers affect glucose metabolism and may mask some important premonitory signs of acute hypoglycaemia, such as tachycardia.
In patients with insulin or non-insulin 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. The dose of insulin or oral hypoglycaemic agent may need adjustment. Diabetic patients receiving Minax should be monitored to ensure that diabetes control is maintained.

Allergic conditions.

Allergic reactions may be exaggerated by β-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.
In patients taking β-blockers, anaphylactic shock assumes a more severe form and may be resistant to normal doses of adrenaline (epinephrine). Whenever possible, β-blockers should be avoided in patients who are at increased risk of anaphylaxis.

Hyperthyroidism.

Special care should be exercised in those patients who are hyperthyroid and are also receiving β-blockers because β-blockers may mask the clinical signs of developing or continuing hyperthyroidism, resulting in symptomatic improvement without any change in thyroid status. Where Minax is administered to patients having, or suspected of developing thyrotoxicosis, both thyroid and cardiac function should be monitored closely.

Peripheral vascular disease.

Beta-blockade may impair the peripheral circulation and exacerbate the symptoms of peripheral vascular disease (see Section 4.3 Contraindications).

Use in hepatic impairment.

Metoprolol is mainly eliminated by means of hepatic metabolism (see Section 5.2 Pharmacokinetic Properties). Therefore, liver cirrhosis may increase the systemic bioavailability of metoprolol and reduce its total clearance, leading to increased plasma concentrations.

Use in renal impairment.

In patients with severe renal disease, haemodynamic changes following β-blockade may impair renal function further. Beta-blockers which are excreted mainly by the kidney may require dose adjustment in patients with renal failure.

Use in the elderly.

Caution is indicated in elderly patients. An excessive decrease in blood pressure or pulse rate may cause the blood supply to vital organs to fall to inadequate levels.

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. Extreme caution is required if these drugs have to be used together.
A calcium channel blocker of the phenylalkylamine type (e.g. verapamil) should not be administered intravenously to patients receiving metoprolol because there is a risk of cardiac arrest in this situation. Patients taking an oral calcium channel blocker of this type in combination with metoprolol should be closely monitored.
The combination of β-blockers with dihydropyridine calcium channel blockers with a weak myocardial depressant effect (e.g. felodipine, nifedipine) can be administered together with caution. In case excess hypotension develops, the calcium antagonist should be stopped or the dosage 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, tocainide, mexiletine and lidocaine (lignocaine); class IC agents, flecainide and propafenone (not available in Australia); the class III agent amiodarone; and the class IV agents (e.g. verapamil).

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.

Catecholamine-depleting agents.

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

General anaesthetics.

Beta-blockade may have beneficial effects in decreasing the incidence of arrhythmias and myocardial ischaemia during anaesthesia and the post-operative period. It is currently recommended that maintenance β-blockade be continued peri-operatively. 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.
Acute initiation of high dose metoprolol to patients undergoing non-cardiac surgery should be avoided, since it has been associated with bradycardia, hypotension and stroke including fatal outcome in patients with cardiovascular risk factors.
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 β-blockade. If it is thought necessary to withdraw β-blocker therapy before surgery, this should be done gradually and completed about 48 hours before surgery (see Section 4.4 Special Warnings and Precautions for Use, Abrupt withdrawal).

Effects on the heart rate.

If the patient develops increasing bradycardia (heart rate less than 50 to 55 beats/minute), the dosage of Minax should be gradually reduced or treatment gradually withdrawn (see Section 4.3 Contraindications).

Effects on the thyroid.

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.

Other metabolic effects.

Beta-adrenoceptors 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.

Effects on the eye and skin.

Various rashes and conjunctival xeroses have been reported with β-blocking agents. Cross reactions may occur between β-blockers, therefore substitutions within the group may not necessarily preclude occurrence of symptoms.
During 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. On a few rare occasions, serous otitis media, sclerosing peritonitis, pericarditis and pleurisy have been reported.
The oculomucocutaneous syndrome as reported with practolol has not been reported with metoprolol. However, dry eyes and skin rash have been reported with metoprolol. If such symptoms occur, discontinuation of metoprolol should be considered.
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.

Abrupt withdrawal.

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 have 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 8-14 days during which time the patient's progress should be assessed. Minax should be temporarily reinstituted if the angina worsens.
If the drug must be withdrawn abruptly in these patients, close observation is required. In the peri-operative period, metoprolol should not be withdrawn unless indicated.

Paediatric use.

The safety and efficacy in children have not been established.

Effect on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Other anti-hypertensive agents.

Metoprolol enhances the effect of other antihypertensive drugs. Particular caution is required when administering a β-blocker and prazosin together for the first time.

Sympathetic ganglion blocking agents, other beta-blockers or monoamine oxidase (MAO) inhibitors.

Patients receiving concurrent treatment with sympathetic ganglion blocking agents, other β-blockers (including eye drops), or monoamine oxidase (MAO) inhibitors should be carefully monitored.

Clonidine.

If concomitant treatment with clonidine is to be discontinued, the β-blocker medication should be withdrawn several days before clonidine. The rebound hypertension associated with clonidine withdrawal can be exacerbated by the presence of a β-blocker. If both drugs are withdrawn simultaneously, marked rise in blood pressure, and/or arrhythmias may result.

Calcium antagonists.

When metoprolol is given together with calcium antagonists of the verapamil and diltiazem type and/or anti-arrhythmic agents, the patient should be monitored for possible negative inotropic and chronotropic effects. Calcium antagonists of the verapamil type should not be given by intravenous administration to patients treated with β-blockers.

Anti-arrhythmic agents.

When metoprolol is given together with anti-arrhythmic agents the patient should be monitored for possible negative inotropic and chronotropic effects. The negative inotropic and negative chronotropic effects of antiarrhythmic agents of the quinidine type and amiodarone may be enhanced by beta-blockers.

Prostaglandin synthetase inhibiting agents.

Concurrent treatment with indomethacin or other prostaglandin synthetase inhibiting agents may decrease the antihypertensive effect of β-blockers.

Alcohol.

Metoprolol may modify the pharmacokinetic behaviour of alcohol when taken concomitantly. The plasma level of metoprolol may be raised by alcohol.

Liver enzyme effects.

Enzyme-inducing and enzyme-inhibiting substances may change the plasma concentration of metoprolol. The plasma concentration of metoprolol is lowered by rifampicin and may be raised by cimetidine, alcohol, hydralazine and selective serotonin reuptake inhibitors (SSRIs), e.g. paroxetine, fluoxetine and sertraline.

Oral antidiabetic agents.

The dosage of oral antidiabetics may need to be adjusted in patients receiving β-blockers (see Section 4.4 Special Warnings and Precautions for Use).

Anaesthetics.

Inhalation anaesthetics enhance the cardiodepressant effect of β-blocker therapy (see Section 4.4 Special Warnings and Precautions for Use). Metoprolol may also reduce the clearance of other drugs (e.g. lidocaine (lignocaine)).

Warfarin.

A limited number of reports have demonstrated a rise in AUC and concentration of warfarin when taken with another β-blocker. This could potentially increase the anticoagulant effect of warfarin.

Digitalis glycosides.

Digitalis glycosides, in association with beta-blockers, may increase atrioventricular conduction time and may induce bradycardia.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
Metoprolol should not be given during pregnancy unless its use is considered essential. In general, β-blockers reduce placental perfusion, which has been associated with growth retardation, intrauterine death, abortion and early labour. It is therefore suggested that appropriate maternofetal monitoring be performed in pregnant women treated with metoprolol.
β-blockers may cause bradycardia in the foetus and newborn infant.
Metoprolol crosses the placental barrier in pregnant women; in one study the concentration in the umbilical vein was almost the same as in maternal vein plasma.
During the later stages of pregnancy, these drugs should only be given after weighing the needs of the mother against the risk to the foetus.
The lowest possible dose should be used and discontinuation of treatment should be considered at least 2 to 3 days before delivery to avoid increased uterine contractility and effects of β-blockade in the newborn (e.g. bradycardia, hypoglycaemia).
 Metoprolol is excreted in human breast milk. Beta-blockers taken by the mother may cause side effects, e.g. bradycardia, in the breastfed infant, although when the doses used are within the recommended therapeutic range, the very small amount of drug ingested by the infant renders such effects unlikely. Nevertheless, breastfed infants should be closely observed for signs or symptoms of β-blockade.
Experience suggests that metoprolol only need be discontinued during lactation if the infant's hepatic function is severely impaired.

4.7 Effects on Ability to Drive and Use Machines

Minax may cause dizziness, fatigue or visual disturbances (see Section 4.8 Adverse Effects (Undesirable Effects)) and, therefore, may adversely affect the patient's ability to drive or use machinery.

4.8 Adverse Effects (Undesirable Effects)

Occasionally, especially at the start of treatment, beta-blockers may give rise to gastrointestinal upsets, sleep disturbances, or exertional tiredness. These effects, however, are of a mild nature and seldom necessitate a reduction in the dosage.
The following events have been reported as adverse events in clinical trials or reported from routine use. In many cases a relationship with metoprolol has not been established. The following definitions of frequency are used: very common ≥ 10%; common 1-9.9%; uncommon 0.1-0.9%; rare 0.01-0.09%; very rare < 0.01%.

Cardiovascular.

Common: bradycardia, postural disorders (very rarely with syncope), cold hands and feet (Raynaud's phenomenon), palpitations, clinically significant falls in blood pressure after intravenous administration.
Uncommon: transient deterioration of heart failure symptoms, A-V block I, oedema, precordial pain cardiogenic shock in patients with acute myocardial infarction*.
Rare: disturbances of cardiac conduction, cardiac arrhythmias.
Very rare: gangrene in patients with pre-existing severe peripheral circulatory disorders.
*Excess frequency of 0.4% compared with placebo in a study of 46,000 patients with acute myocardial infarction where the frequency of cardiogenic shock was 2.3% in the metoprolol group and 1.9% in the placebo group in the subset of patients with low shock risk index. The shock risk index was based on the absolute risk of shock in each individual patient derived from age, sex, time delay, Killip class, blood pressure, heart rate, ECG abnormality, and prior history of hypertension. The patient group with low shock risk index corresponds to the patients in which metoprolol is recommended for use in acute myocardial infarction.

Central nervous system.

Very common: fatigue.
Common: dizziness, headache.
Uncommon: paraesthesia, muscle cramps.

Gastrointestinal.

Common: nausea, diarrhoea, constipation, abdominal pain.
Uncommon: vomiting.
Rare: dry mouth.

Haematologic.

Very rare: thrombocytopenia.

Hepatic.

Rare: liver function test abnormalities.
Very rare: hepatitis.

Metabolic.

Uncommon: weight gain.

Psychiatric.

Uncommon: depression, impaired concentration, somnolence or insomnia, nightmares.
Rare: nervousness, anxiety, impotence/ sexual dysfunction.
Very rare: amnesia/ memory impairment, confusion, hallucinations.

Respiratory.

Common: dyspnoea on exertion.
Uncommon: bronchospasm (which may also occur in patients without a history of obstructive lung disease).
Rare: rhinitis.

Sense organs.

Rare: disturbances of vision, dry and/or irritated eyes, conjunctivitis (see Section 4.4 Special Warnings and Precautions for Use).
Very rare: tinnitus, taste disturbances.

Skin.

Uncommon: rash (in the form of urticaria, psoriasiform and dystrophic skin lesions), increased sweating.
Rare: loss of hair.
Very rare: photosensitivity reactions, aggravated psoriasis.

Miscellaneous.

Very rare: arthralgia.

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.

4.9 Overdose

Symptoms.

Symptoms of overdosage may include severe hypotension, cardiac insufficiency, bradycardia and bradyarrhythmia, cardiac conduction disturbances, cardiogenic shock, cardiac arrest, impairment of consciousness/coma, convulsions and bronchospasm. The main clinical signs of overdosage are cardiovascular and in some cases decompensation may be rapid. Overdosage with Minax can lead to death.
Cases of overdosage in paediatric patients need to be given extra attention even if the patient appears well on presentation and even if only a small number of tablets have apparently been taken.

Management.

Care should be provided at a facility that can provide appropriate supporting measures, monitoring, and supervision.
Activated charcoal may reduce absorption of the medicine 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.
Syrup of ipecac and gastric lavage are no longer considered to be standard therapy for gut decontamination.
Atropine, adreno-stimulating drugs or pacemaker to treat bradycardia and conduction disorders.
Hypotension, acute cardiac failure, and shock to be treated with suitable volume expansion, injection of glucagon (if necessary, followed by an intravenous infusion of glucagon), intravenous administration of adreno-stimulating drugs such as dobutamine, with α1-receptor agonistic drugs added in presence of vasodilation. Intravenous use of calcium salts (Ca2+) can also be considered.
Bronchospasm can usually be reversed by bronchodilators.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Metoprolol is a relatively cardioselective beta-adrenoceptor blocking drug without intrinsic sympathomimetic activity, and is suited for the treatment of hypertension. It acts on β1-receptors mainly located in the heart at lower doses than those needed to influence the β2-receptors mainly located in the bronchi and peripheral vessels. Metoprolol reduces the blood pressure in patients with hypertension, in both the standing and supine position. It also reduces the extent of rises in blood pressure occurring in response to physical and mental stress.
In angina pectoris, metoprolol decreases the frequency and severity of the attacks, and the need for glyceryl trinitrate relief, and increases exercise tolerance.
Metoprolol has been shown to reduce mortality in patients with suspected or definite myocardial infarction. The mechanisms of action for these effects of metoprolol are not fully understood but may be related to a lower incidence of ventricular fibrillation, and limitation of infarct size. Metoprolol has also been shown to reduce the incidence of recurrent myocardial infarction.
In cases of supraventricular tachycardia or atrial fibrillation, and in the presence of extrasystoles, metoprolol has a regulating effect on the heart rate.
Orthostatic reactions or disturbances of electrolyte balance have not been observed.
In therapeutic doses, metoprolol has less effect on peripheral circulation and the bronchial muscles than nonselective β-blockers. However, it should be used with caution in patients with asthma, and concomitant use of an adrenergic bronchodilator, e.g. terbutaline or salbutamol, is recommended. Patients already taking β2-stimulants for reversible airways obstruction may require adjustment of dosage of these if metoprolol therapy is subsequently introduced.
The stimulant effect of catecholamines on the heart is reduced or inhibited by metoprolol. This leads to a decrease in heart rate, cardiac contractility and cardiac output. Metoprolol inhibits catecholamine-induced lipolysis.
Metoprolol has been shown to reduce diuretic-induced increase in plasma renin activity. It inhibits catecholamine-induced insulin secretion to a far lesser degree than nonselective β-blockers.
Metoprolol is practically devoid of membrane-stabilising activity, does not display partial agonist activity, i.e. intrinsic sympathomimetic activity (ISA), at doses required to produce β-blockade.
Metoprolol forms an active metabolite (2-hydroxymetoprolol), which does not, however, contribute significantly to the therapeutic effect.
Metoprolol is considered a relatively lipid-soluble compound i.e. less soluble than propranolol and more lipid soluble than atenolol.
Metoprolol has been shown to exert a prophylactic effect in both classical and common migraine.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption and distribution.

Metoprolol is rapidly and almost completely (more than 95%) absorbed from the gastrointestinal tract. It is rapidly and extensively distributed to the extravascular tissue. The volume of distribution is 5.6 L/kg. At therapeutic concentrations approximately 12% of metoprolol is bound to human serum proteins.

Metabolism and excretion.

Studies with radioactively labelled drug have shown that more than 90% of the dose is excreted in the urine in 72 hours, mainly in the form of known metabolites. Only about 3% of the administered dose is excreted unchanged in the urine in 72 hours. The rate of renal excretion of metoprolol has a linear relationship to its plasma concentration. Metoprolol is excreted mainly by glomerular filtration.
Long-term studies have shown that metoprolol neither enhances nor inhibits its own metabolism.
The elimination half-life of metoprolol is between 3 and 5 hours.

Dose-response.

The duration of the β-blocking effects is dose dependent (as measured by reduction of exercise heart rate). For instance, in healthy subjects the effect of 20 mg metoprolol given intravenously is halved after about 6 hours.

Pharmacokinetics in the elderly.

Elderly subjects showed no significant differences in the plasma concentrations of metoprolol as compared with young persons, in a study involving eight healthy elderly individuals (mean age 74.5 years) and eight young subjects (mean age 26.3 years).

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Minax 50 tablets contain lactose monohydrate, microcrystalline cellulose, povidone, colloidal anhydrous silica, sodium starch glycollate and magnesium stearate.
Minax 100 tablets contain lactose monohydrate, microcrystalline cellulose, povidone, purified talc, colloidal anhydrous silica, sodium starch glycollate, carmellose sodium and magnesium stearate.

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

Blister pack.

Store below 30°C.

Bottle.

Store below 25°C.

6.5 Nature and Contents of Container

Minax 50.

Pack sizes: available in PVC/PVDC/Al blister and HDPE bottle packs of 100's.

Minax 100.

Pack sizes: available in PVC/PVDC/Al blister and HDPE bottle packs of 60's.
Some strengths, pack sizes and/or pack types may not be marketed.

Australian register of therapeutic goods (ARTG).

AUST R 34408 - Minax 50 metoprolol tartrate 50 mg tablet bottle.
AUST R 34410 - Minax 100 metoprolol tartrate 100 mg tablet bottle.
AUST R 42749 - Minax 50 metoprolol tartrate 50 mg tablet blister pack.
AUST R 42750 - Minax 100 metoprolol tartrate 100 mg tablet blister pack.

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.

6.7 Physicochemical Properties

Metoprolol tartrate, an aryloxypropanolamine derivative, is a white crystalline powder with a melting point of 120°C. The powder is odourless or almost odourless. It is very soluble in water, soluble in chloroform, methylene chloride and alcohol, and almost insoluble in benzene, diethylether and acetone.

Chemical structure.

Chemical name: di-[(±)-1-(isopropylamino)- 3-[p-(2-methoxyethyl) phenoxy]-2- propanol] L(+)-tartrate.
Structural formula:
Molecular formula: (C15H25NO3)2.C4H6O6. Molecular weight: 685.

CAS number.

56392-17-7.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes