Consumer medicine information

ARX-Metoprolol (was Metrol)

Metoprolol tartrate

BRAND INFORMATION

Brand name

ARX-Metoprolol (was Metrol)

Active ingredient

Metoprolol tartrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using ARX-Metoprolol (was Metrol).

SUMMARY CMI

ARX-METOPROLOL TABLETS

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using ARX-METOPROLOL tablets?

ARX-METOPROLOL tablets contains the active ingredient metoprolol tartrate. ARX-METOPROLOL tablets are used to lower high blood pressure (also called hypertension), prevent angina, treat or prevent heart attacks, or reduce your risk of heart complications following a heart attack or to prevent migraine headaches

For more information, see Section 1. Why am I using ARX-METOPROLOL tablets? in the full CMI.

2. What should I know before I use ARX-METOPROLOL tablets?

Do not use if you have ever had an allergic reaction to ARX-METOPROLOL or any of the ingredients listed at the end of the CMI, if 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 or if you are receiving/having emergency treatment for shock or severely low blood pressure.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use ARX-METOPROLOL tablets? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with ARX-METOPROLOL tablets and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use ARX-METOPROLOL tablets?

  • ARX-METOPROLOL tablets are available as either 50mg or 100mg tablets. The dose of ARX-METOPROLOL tablets depends on what condition you are being treated for. Your doctor will tell you what dose to take.
  • Swallow the tablet with a glass of fluid.

More instructions can be found in Section 4. How do I use ARX-METOPROLOL tablets? in the full CMI.

5. What should I know while using ARX-METOPROLOL tablets?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using ARX-METOPROLOL.
  • Be sure to keep all of your doctor's appointments so that your progress can be checked.
  • If you feel light-headed, dizzy or faint when getting out of bed or standing up, get up slowly.
  • Make sure you drink enough water during exercise and hot weather when you are taking ARX-METOPROLOL, especially if you sweat a lot.
  • If you are being treated for diabetes, make sure you check your blood sugar level regularly and report any changes to your doctor.
Things you should not do
  • Do not stop using this medicine suddenly without checking with your doctor.
Looking after your medicine
  • Keep your tablets in the blister pack until it is time to take them.

For more information, see Section 5. What should I know while using ARX-METOPROLOL? in the full CMI.

6. Are there any side effects?

All medicines can have side effects. If you do experience side effects, most of them are minor and temporary. However, some side effects may be serious and could require urgent medical attention or hospitalization. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

ARX-METOPROLOL TABLETS

Active ingredient(s): metoprolol tartrate

Consumer Medicine Information (CMI)

This leaflet provides important information about using ARX-METOPROLOL tablets. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using ARX-METOPROLOL tablets.

Where to find information in this leaflet:

1. Why am I using ARX-METOPROLOL tablets?
2. What should I know before I use ARX-METOPROLOL tablets?
3. What if I am taking other medicines?
4. How do I use ARX-METOPROLOL tablets?
5. What should I know while using ARX-METOPROLOL tablets?
6. Are there any side effects?
7. Product details

1. Why am I using ARX-METOPROLOL tablets?

ARX-METOPROLOL tablets contains the active ingredient metoprolol tartrate. ARX-METOPROLOL tablets belongs to a group of medicines called beta-blockers.

ARX-METOPROLOL tablets are used to:

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

It 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 that the heart has to do. It also widens the blood vessels in the rest of the body, as well as helping the heart to beat more regularly.

2. What should I know before I use ARX-METOPROLOL tablets?

Warnings

Do not use ARX-METOPROLOL tablets if:

  • you are allergic to metoprolol tartrate, 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 severe 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 to 50 beats per minute)
  • you have certain other heart conditions
  • you have phaeochromocytoma (a rare tumour of the adrenal gland) which is not already being treated 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.

Check with your doctor if you:

  • are not sure whether any of the above apply to you
  • have any other medical conditions
  • take any medicines for any other condition

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Like most beta-blocker medicines, ARX-METOPROLOL is not recommended for use during pregnancy.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

The active ingredient in ARX-METOPROLOL passes into breast milk and therefore there is a possibility that the breastfed baby may be affected.

Children and Adolescent

Do not give ARX-METOPROLOL to children.

The safety and effectiveness of ARX-METOPROLOL in children has not been established.

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
  • 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

3. What if I am taking other medicines?

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

Some medicines may interfere with ARX-METOPROLOL tablets and affect how it works. These include:

  • Other beta-blocker medicines, including beta-blocker eye drops
  • calcium channel blockers or calcium antagonists, medicines used to treat high blood pressure and angina for example verapamil or diltiazem
  • medicines used to treat high blood pressure, for example clonidine, hydrazine, and prazosin
  • medicines used to treat abnormal or irregular heart beat for example amiodarone, disopyramide and quinidine
  • medicines used to treat arthritis, pain, or inflammation for example indomethacin 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 for 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 ARX-METOPROLOL or may affect how well it works. You may need to take 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 ARX-METOPROLOL.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect ARX-METOPROLOL tablets.

4. How do I use ARX-METOPROLOL tablets?

How much to take

For high blood pressure:

  • The usual starting dose is one 50mg or 100mg tablet once a day for one week.
  • The dose is then usually increased to 50mg or 100mg once or twice daily.
  • Your doctor may tell you to take a different amount of ARX-METOPROLOL.
    Follow your doctors the 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 starting dose is one 50mg or 100mg taken two or three times a day.

After myocardial infarction (heart attack):

  • The usual starting dose is 100mg taken twice a day, often starting with a lower dose for 2 days.

For migraine prevention:

  • The usual dose is 100-150mg taken twice 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 ARX-METOPROLOL

Swallow the tablet with a full glass of fluid.

When to take ARX-METOPROLOL

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 ARX-METOPROLOL

Continue taking your medicine for as long as your doctor tells you. This medicine helps to control your condition, but it does not cure it.

It is important to keep taking your medicine even if you feel well.

DO NOT STOP TAKING ARX-METOPROLOL 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 use ARX-METOPROLOL tablets

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

Otherwise, take it 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 use too much ARX-METOPROLOL tablets

If you think that you have used too much ARX-METOPROLOL tablets, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

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

If you take too many ARX-METOPROLOL tablets your blood pressure may drop too far. You will feel 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.

5. What should I know while using ARX-METOPROLOL tablets?

Things you should do

Be sure to keep all of your doctor's appointments so that your progress can be checked.

Elderly patients especially need to be monitored to stop their blood pressure falling too far.

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 ARX-METOPROLOL.

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 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 this medicine, especially if you sweat a lot.

If you do not drink enough water while taking this medicine, 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.

ARX-METOPROLOL may change how well your diabetes is controlled. It may also cover up some of the symptoms of low blood sugar (hypoglycaemia). ARX-METOPROLOL may increase the time your body takes to recover from low blood sugar. Your doses of diabetic medicines, including insulin, may need to change.

Call your doctor straight away if you:

  • become pregnant while taking ARX-METOPROLOL
  • have a severe allergic reaction to foods, medicines or insect stings

If you have a history of allergies, there is a chance that ARX-METOPROLOL may cause allergic reactions to be worse and harder to treat.

If you are about to be started on a new medicine, remind your doctor and pharmacist that you are taking ARX-METOPROLOL.

  • Tell any doctors, dentists, and pharmacists who are treating you that you are taking ARX-METOPROLOL.
  • If you plan to have a surgery (even at the dentist) that need an anaesthetic, tell your doctor or dentist that you are taking ARX-METOPROLOL.
  • If you have to have any medical tests while you are taking ARX-METOPROLOL, tell your doctor.
    ARX-METOPROLOL may affect the results of some tests.

Things you should not do

  • Do not stop using this medicine suddenly without checking with your doctor.
    Your doctor may want you to gradually reduce the amount of ARX-METOPROLOL you are taking before stopping completely. This may help reduce the possibility of your condition getting worse.
  • Do not give ARX-METOPROLOL to anyone else even if they have the same condition as you.
  • Do not use ARX-METOPROLOL to treat any other complaints unless your doctor tells you to.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how ARX-METOPROLOL tablets affects you.

As with other beta-blocker medicines, ARX-METOPROLOL may cause dizziness, light-headedness, tiredness, or drowsiness in some people. Make sure you know how you react to ARX-METOPROLOL before you drive a car, operate machinery, or do anything else that could be dangerous if you are dizzy or light-headed.

Drinking alcohol

Tell your doctor if you drink alcohol.

If you drink alcohol, dizziness or light-headedness may be worse.

Dress warmly during cold weather, especially if you will be outside for a long time (for example when playing winter sports).

ARX-METOPROLOL like other beta-blocker medicines, may make you more sensitive to cold temperatures especially if you have circulation problems.

Looking after your medicine

Keep your tablets in the blister pack until it is time to take them.

If you take ARX-METOPROLOL out of the blister pack it will not keep well.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place where the temperature stays below 25°C, away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Heat and dampness can destroy some medicines.

Keep it where young children cannot reach it.

When to discard your medicine

Do not take ARX-METOPROLOL if the expiry date printed on the pack has passed 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.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

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

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
  • headache, tiredness, drowsiness, weakness, or lack of energy
  • aches and pains, painful joints
  • nausea (feeling sick), vomiting
  • stomach upset, diarrhoea or constipation, weight gain
  • dry mouth, changes in taste sensation
  • difficulty sleeping, nightmares
  • mood changes
  • confusion, short-term memory loss, inability to concentrate
  • increased sweating, runny or blocked nose
  • hair loss
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • dizziness, lightheadedness or fainting especially on standing up, which may be due to low blood pressure
  • tingling or “pins and needles”
  • coldness, burning, numbness or pain in arms and/or legs
  • skin rash or worsening of psoriasis
  • sunburn happening more quickly than usual
  • abnormal thinking or hallucinations
  • buzzing or ringing in the ears, deafness
  • irritated eyes or blurred vision
  • sexual problems
  • constant "flu-like" symptoms with tiredness or lack of energy
  • unusual bleeding or bruising
Serious side effects are rare.		Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Very serious side effects

Very serious side effectsWhat to do
  • shortness of breath, being less able to exercise
  • swelling of the ankles, feet or legs
  • chest tightness, wheezing, noisy breathing, difficulty 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 skin or eyes (jaundice), generally feeling unwell
These side effects are rare.		Call your doctor straight away, or go straight to the Emergency at your nearest hospital if you notice any of these very serious side effects.
You may need urgent medical attention or hospitalization.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

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

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What ARX-METOPROLOL tablets contains

Active ingredient
(main ingredient)		metoprolol tartrate
Other ingredients
(inactive ingredients)
  • lactose monohydrate
  • maize starch
  • microcrystalline cellulose
  • magnesium stearate
  • colloidal anhydrous silica
  • hyprolose
  • calcium hydrogen phosphate dihydrate
  • crospovidone
Potential allergenssugars as lactose

Do not take this medicine if you are allergic to any of these ingredients.

What ARX-METOPROLOL tablets looks like

ARX-METOPROLOL 50 is round, white tablet, scored on one side. AUST R 75835.

A blister pack contains 100 tablets.

ARX-METOPROLOL 100 is round, white tablet, scored on one side. AUST R 75834.

A blister pack contains 60 tablets.

Who distributes ARX-METOPROLOL tablets

Arrotex Pharmaceuticals
15-17 Chapel Street
Cremorne VIC 3121
www.arrotex.com.au

This leaflet was prepared in February 2025.

Published by MIMS April 2025

BRAND INFORMATION

Brand name

ARX-Metoprolol (was Metrol)

Active ingredient

Metoprolol tartrate

Schedule

S4

 

1 Name of Medicine

Metoprolol tartrate.

2 Qualitative and Quantitative Composition

Each ARX-Metoprolol 50 mg tablet contains 50 mg metoprolol tartrate.
Each ARX-Metoprolol 100 mg tablet contains 100 mg metoprolol tartrate.

Excipients with known effect.

Contains sugars as lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

ARX-Metoprolol 50 mg tablets.

White, round, biconvex, with a score notch on one side (7.0 - 7.2 mm diameter).

ARX-Metoprolol 100 mg tablets.

White, round, biconvex, with a score notch on one side (9.0 - 9.2 diameter).

4 Clinical Particulars

4.1 Therapeutic Indications

Hypertension; angina pectoris prophylaxis; suspected or definite myocardial infarction; migraine prophylaxis.

4.2 Dose and Method of Administration

ARX-Metoprolol is recommended for oral therapy in hypertension, angina pectoris, suspected or definite myocardial infarction and migraine prophylaxis.

Hypertension.

Initially.

Mild hypertensives: 50 or 100 mg once daily, for one week.
Severe hypertensives: 50 or 100 mg twice daily for one week.

Maintenance.

50 or 100 mg once or twice daily.
Some patients will respond to 50 mg once daily. However, a large number of patients 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 patients where maintenance dosage is 150 mg daily or less, it may be administered as a single dose.

Angina pectoris.

50 to 100 mg two or three times daily.

Myocardial infarction.

Initially.

Therapy should commence with ARX-Metoprolol 50 mg tablets twice daily and be continued for 48 hours.

Maintenance.

The oral maintenance dose is generally 100 mg twice daily.

Migraine prophylaxis.

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

4.3 Contraindications

Bronchospasm. β-Adrenergic blockade of the smooth muscle of bronchioles may result in an increased airways resistance. These medicines 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.
Allergic disorders (including allergic rhinitis) which may suggest a predisposition to bronchospasm.
Right ventricular failure secondary to pulmonary hypertension.
Significant right ventricular hypertrophy.
Sinus bradycardia (less than 45 to 50 beats/minute).
Second and third degree atrioventricular block.
Shock (including cardiogenic and hypovolaemic shock).
Hypersensitivity to metoprolol tartrate, related derivatives.
Hypersensitivity to any of the excipients in ARX-Metoprolol.
Sensitivity to other β-blockers as cross sensitivity between β-blockers can occur.
Non-compensated congestive heart failure (see Section 4.4 Special Warnings and Precautions for Use).
Sick-sinus syndrome (unless a permanent, appropriately functioning pacemaker is in place).
Severe peripheral arterial circulatory disorders.
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.
Hypotension.
Untreated phaeochromocytoma (see Section 4.4 Special Warnings and Precautions for Use).
Continuous or intermittent inotropic therapy acting through β-receptor agonism.

4.4 Special Warnings and Precautions for Use

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. 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 develops metoprolol should be discontinued gradually (see Section 4.4 Special Warnings and Precautions for Use, Abrupt withdrawal). β-blockers should not be used in patients with uncontrolled 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 growing literature on the experimental use of β-adrenergic blocking medicines in heart failure. As further trials are needed to identify which patients are most likely to respond to which medicines, β-blockers including metoprolol should not normally be prescribed for heart failure outside specialist centres.

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 8 to 14 days during which time the patient's progress should be assessed. Metoprolol should be temporarily reinstituted if the angina worsens. If the medicine must be withdrawn abruptly in these patients, close observation is required. In the perioperative period, metoprolol should not be withdrawn unless withdrawal is specifically indicated.

Effects on the heart rate.

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

Peripheral vascular disease.

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

Prinzmetal angina.

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

Diabetes.

Metoprolol should be used with caution in patients with diabetes mellitus, especially those who are receiving insulin or oral hypoglycaemic agents. Diabetes patients should be warned that β-blockers including metoprolol 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 to be adjusted. Diabetic patients receiving metoprolol should be monitored to ensure that diabetes control is maintained.

Other metabolic effects.

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

Phaeochromocytoma.

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

Effects on the eye and skin.

Various skin rashes and conjunctival xerosis 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 medicine 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 or practolol syndrome. On a few rare occasions, serious otitis media, sclerosing peritonitis and pleurisy have been reported as part of this syndrome.
The oculomucocutaneous syndrome 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.

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). β-blockers, including metoprolol, should be avoided if there is a risk of bronchospasm.
In patients taking β-blockers including metoprolol, anaphylactic shock assumes a more severe form and may be resistant to normal doses of adrenaline. Whenever possible, β-blockers including metoprolol 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 also receiving beta-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 metoprolol is administered to patients having, or suspected of developing thyrotoxicosis, both thyroid and cardiac function should be monitored closely.

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.

Conduction disorders.

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

Concomitant therapy with calcium antagonists.

The concomitant use of calcium antagonists with myocardial suppressant and sinus node activity (e.g. verapamil and to a lesser extent diltiazem) and β-blockers may cause bradycardia, hypotension and asystole. Extreme caution is required if these medicines have to be used together. A calcium antagonist of the phenylalkylamine type (i.e. 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 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 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.

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.

Antiarrhythmic medicines.

Care should be taken when prescribing β-blockers with antiarrhythmic medicines. 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 lignocaine; class IC agents, flecainide and propafenone (not available in Australia); the class III agent, amiodarone; and the class IV antiarrhythmic agents (e.g. verapamil).

Catecholamine depleting agents.

Concomitant use of medicines 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 anaesthesia.

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 medicines, 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 be completed about 48 hours before surgery (see Section 4.4 Special Warnings and Precautions for Use, Abrupt withdrawal).

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. β-blockers, which are excreted mainly by the kidney, may require dose adjustment in patients with renal failure.

Use in the elderly.

See Section 5.2 Pharmacokinetic Properties, Pharmacokinetics in the elderly.

Paediatric use.

The safety and efficacy of metoprolol in children have not been established.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Calcium antagonists.

When metoprolol is given together with calcium antagonists of the verapamil and diltiazem type 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 antiarrhythmic 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 β-blockers.

Clonidine.

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

Other anti-hypertensive agents.

Metoprolol enhances the effects of other antihypertensive medicines. Particular care is required when initiating administration of a β-blocker and prazosin together.

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

Patients receiving concomitant treatment with sympathetic ganglion blocking agents, other β-blockers (including eye drops), or monoamine oxidase (MAO) inhibitors should be kept under close surveillance.

Prostaglandin synthetase inhibiting agents.

Concomitant 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 together. The plasma level of metoprolol may be raised by alcohol.

Liver enzyme effects.

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

Oral antidiabetic drugs.

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

Anaesthetics.

Inhalation anaesthetics enhance the cardiosuppressant effect of beta-blocker therapy (see Section 4.4 Special Warnings and Precautions for Use). Metoprolol may also reduce the clearance of other drugs (e.g. 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. Beta-blockers may cause bradycardia in the foetus and new-born 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 medicines 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 treatment should be discontinued 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. β-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 the drug ingested by the infant renders such effects unlikely. 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

Metoprolol 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, β-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 medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at https://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 ARX-Metoprolol 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.

Treatment.

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 tartrate is structurally related to other cardioselective β-blockers. It is a relatively cardioselective β-adrenoceptor blocking medicine 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 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 reduces 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 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 extra systoles, metoprolol has a regulating effect on the heart rate.
Orthostatic effects or disturbances of electrolyte balance have not been observed.
In therapeutic doses, metoprolol has less effect on the peripheral circulation and the bronchial muscles than non-selective β-blockers. However, metoprolol should be used with caution in patients with asthma, and concomitant use of an adrenergic bronchodilator, e.g. terbutaline or salbutamol, is advisable. Patients with reversible airways obstruction who are already taking β2-stimulants may require adjustment of the 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 will inhibit catecholamine induced lipolysis.
It has also been shown to reduce diuretic induced increases in plasma renin activity. Metoprolol will inhibit catecholamine induced insulin secretion to a far lesser degree than non-selective β-blockers.
Metoprolol is practically devoid of membrane stabilising activity and does not display partial agonist activity (i.e. intrinsic sympathomimetic activity = ISA) at doses required to produce β-blockade.
Metoprolol tartrate forms an active metabolite 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. It 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 tissues. The volume of distribution is 5.6 L/kg. At therapeutic concentrations, approximately 12% is bound to human serum proteins.

Metabolism and excretion.

Studies with the radioactively labelled drug have shown that more than 90% of the dose is excreted in the urine within 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 tartrate is between three and five hours.

Dose-response.

The duration of the β-blocking effect is dose dependent (as measured by reduction of exercise heart rate). For instance, in healthy subjects the effect of 20 mg metoprolol tartrate 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 subjects, in a study involving eight healthy elderly (mean age 74.5 years) and eight healthy young (mean age 26.3 years) subjects.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Metoprolol tartrate contains the following excipients: lactose monohydrate, maize starch, microcrystalline cellulose, magnesium stearate, colloidal anhydrous silica, hyprolose, calcium hydrogen phosphate dihydrate and crospovidone.

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 25°C.
Protect from light and moisture.

6.5 Nature and Contents of Container

ARX-Metoprolol 50 mg tablets.

Blister packs (PVC/Al) of 100 tablets.

ARX-Metoprolol 100 mg tablets.

Blister packs (PVC/Al) of 60 tablets.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Metoprolol tartrate is a white crystalline powder. Melting point: approximately 120°C. The powder is practically odourless. It is very soluble in water, soluble in chloroform, methylene chloride and alcohol, and almost insoluble in benzene, diethylether and acetone.
Chemical name: di[(RS)-3-[4-(2-methoxyethyl)phenoxy]-1-(isopropylamino)propan-2-ol] tartrate.
Molecular formula: (C15H25NO3)2.C4H6O6.
Molecular weight: 684.8.

Chemical structure.


CAS number.

Cas No.: 56392-17-7.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription only medicine.

Summary Table of Changes