Consumer medicine information

Metaraminol ARX Injection

Metaraminol

BRAND INFORMATION

Brand name

Metaraminol ARX

Active ingredient

Metaraminol

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Metaraminol ARX Injection.

What is in this leaflet

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

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

If you have any concerns about receiving this medicine, ask your doctor or pharmacist.

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

What this medicine is used for

Metaraminol solution for injection is used to increase your blood pressure, which can drop during spinal anaesthesia or can drop as a reaction to medications or surgical complications.

How this medicine works

Metaraminol solution for injection belongs to a group of medicines called sympathomimetic amines.

It works by strengthening the contraction of the heart muscle and constricting blood vessels to help increase blood pressure.

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

This medicine is not addictive.

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

The effects of this medicine on your ability to drive and use machinery has not been assessed.

There is not enough information to recommend giving metaraminol solution for injection to children.

Before you are given this medicine

When you must not be given this medicine

You should not be given metaraminol solution for injection if you have an allergy to:

  • any medicine containing metaraminol
  • sulfites
  • any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

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

Do not receive this medicine if you are also being given cyclopropane or halothane anaesthesia (unless your doctor decides it is necessary).

Do not give this medicine to a child. Safety and effectiveness in children have not been established.

This medicine should not be given after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. Your doctor or nurse will check to make sure the medicine is not expired or damaged.

If you are not sure whether you should be given this medicine, talk to your doctor.

Before you are given this medicine

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

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

  • Sulfite sensitivity
  • Liver disease
  • Cirrhosis
  • Heart disease
  • Thyroid disease
  • High blood pressure
  • Diabetes
  • Malaria

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

If you have not told your doctor about any of the above, tell him/her before you are given this medicine.

Taking other medicines

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

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

  • Certain medicines used to treat depression, e.g. monoamine oxidase inhibitors (MAOIs) or tricyclic antidepressants (TCAs)
  • Digoxin, a medicine used to treat heart failure.

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

Your doctor will have more information on medicines to be careful with or avoid when you are given this medicine.

How this medicine is given

How it is given

Metaraminol solution for injection is administered in a hospital as an injection into a vein, or it may be diluted before use and given with fluids into a vein. This medicine must only be given by a doctor or nurse.

To reduce microbial hazard, use as soon as practicable after preparation. If storage is necessary, hold at 2-8°C for not more than 24 hours. The injection solution contains no antimicrobial preservative and is for single use in one patient only. Discard any residue.

How much is given

Your doctor will decide on what dose of metaraminol injection you will receive and for how long you will receive it. This will depend on your medical condition and other factors, such as your weight.

If you are given too much (overdose)

Metaraminol solution for injection is administered in a hospital, under the supervision of a doctor. Therefore, it is unlikely that you will receive too much. However, you should tell your doctor or nurse immediately if you feel unwell at all whilst you are being given metaraminol solution for injection. You may need urgent medical attention.

The Poisons information centre can be contacted on 13 11 26 for further advice on overdose management.

While you are being given this medicine

Things you must do

Always follow your doctor’s instructions carefully.

Your doctor or nurse will carefully monitor your blood pressure.

Things to be careful of

Be careful driving or operating machinery until you know how this medicine has affected you. This medicine may cause a fast or pounding heartbeat, and swelling of the face, lips, mouth or throat which may cause difficulty in swallowing or breathing or breathlessness or any difficulty breathing in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Side effects

Tell your doctor as soon as possible if you do not feel well while you are being given this medicine.

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

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

Ask your doctor to answer any questions you may have.

Tell your doctor if you notice any of the following whilst you are being given this medicine:

  • skin problems at the site of injection
  • fast or pounding heartbeat
  • swelling of the face, lips, mouth or throat which may cause difficulty in swallowing or breathing
  • breathlessness or any difficulty breathing.

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

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

Storage and Presentation

Storage

Metaraminol solution for injection should only be given to you in a hospital. It should be kept in the original packaging until it has been given to you.

Metaraminol solution for injection must be stored below 25°C. Protect from light.

Disposal

Any unused or expired medicine should be returned to your pharmacist.

Product description

What it looks like

Metaraminol solution for injection is a clear, colourless sterile solution. It is supplied in a pack of 5 clear glass ampoules.

Ingredients

Metaraminol solution for injection comes in two strengths.

Each ampoule contains metaraminol tartrate equivalent to either
5mg/10mL (AUST R 309267) or
10mg/1mL (AUST R 309266)
of metaraminol.

Each ampoule also contains:

  • sodium chloride in water for injection
  • sodium metabisulfite as a preservative.

This medicine does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Distributor

This medicine is distributed in Australia by:

Arrotex Pharmaceuticals Pty Ltd
15 – 17 Chapel Street
Cremorne VIC 3121

www.arrotex.com.au

This leaflet was prepared in March 2023.

Published by MIMS April 2023

BRAND INFORMATION

Brand name

Metaraminol ARX

Active ingredient

Metaraminol

Schedule

S4

 

1 Name of Medicine

Metaraminol tartrate.

2 Qualitative and Quantitative Composition

Metaraminol injection is available in two strengths and contains either 5 mg/10 mL or 10 mg/1 mL metaraminol (as tartrate) as the active ingredient.

Excipients with known effect.

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

3 Pharmaceutical Form

The injection is a clear colourless sterile solution.

4 Clinical Particulars

4.1 Therapeutic Indications

Prevention and treatment of the acute hypotensive state occurring with spinal anaesthesia; adjunctive treatment of hypotension due to haemorrhage, reactions to medications, surgical complications, and shock associated with brain damage due to tumour or trauma.
It may also be useful as an adjunct in the treatment of hypotension due to cardiogenic shock or septicaemia.

4.2 Dose and Method of Administration

Metaraminol injection is administered intravenously only (injection or infusion) and should be used in one patient on one occasion only. The injection solution contains no antimicrobial preservative and any residue should be discarded.
Because the maximum effect is not immediately apparent, at least ten minutes should elapse before increasing the dosage. As the effect tapers off when the vasopressor is discontinued, the patient should be carefully observed so that therapy can be reinitiated promptly if the blood pressure falls too rapidly. Patients with coexistent shock and acidosis may show a poor response to vasopressors. Established methods of shock management, such as blood or fluid replacement when indicated, and other measures directed to the specific cause of the shock also should be used.

Intravenous infusion (for adjunctive treatment of hypotension).

Metaraminol 10 mg/1 mL Solution for Injection (1 mL ampoule) should be used to prepare the intravenous infusion.
The recommended dose is 15 to 100 mg in 500 mL of sodium chloride injection or glucose injection 5%, adjusting the rate of infusion to maintain the blood pressure at the desired level (see Table 1).
If the patient needs additional saline or glucose solution at a rate of flow that would provide an excessive dose of the vasopressor, the recommended volume (500 mL) of infusion fluid should be increased accordingly. Conversely, if a smaller volume of infusion fluid is desirable, the required dose of metaraminol tartrate may be added to less than 500 mL of diluent.

Compatibility.

In addition to sodium chloride injection and glucose injection 5%, the following infusion solutions were found physically and chemically compatible with metaraminol when 5 mL of metaraminol injection, 10 mg/mL (metaraminol equivalent), was added to 500 mL of infusion solution: Ringer's injection, lactated Ringer's injection, Dextran 6% in saline and Normosol-M in D5-W.
When metaraminol injection is mixed with an infusion solution, sterile precautions should be observed. To reduce microbiological hazard, use as soon as practicable after preparation. If storage is necessary, hold at 2-8°C for not more than 24 hours.
The injection solution contains no antimicrobial preservative and is for single use in one patient only. Discard any residue.

Direct intravenous injection.

In severe shock, when time is of great importance, it may be desirable to administer metaraminol injection by direct intravenous injection. The suggested dose is 0.5 to 5 mg, followed by an infusion of 15 to 100 mg in 500 mL of diluent (see Table 1). Direct intravenous injection of undiluted solution should be employed only in instances of grave emergency when prompt action is imperative to save life. Extreme care must be exercised to give the proper dose.

4.3 Contraindications

Use with cyclopropane or halothane anaesthesia should be avoided, unless clinical circumstances demand such use.
Hypersensitivity to any component of this product including sulfites.

4.4 Special Warnings and Precautions for Use

Identified precautions.

Metaraminol injection contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
Caution should be exercised to avoid an excessive blood pressure response. Rapidly induced hypertensive responses have been reported to cause acute pulmonary oedema, cardiac arrhythmias and arrest. Patients with cirrhosis should be treated with caution, with adequate restoration of electrolytes if diuresis ensues. A fatal ventricular arrhythmia has been reported in a patient with Laennec's cirrhosis while receiving metaraminol tartrate. In several instances, ventricular extrasystoles that appeared during infusion subsided promptly when the rate of flow was reduced.
With the prolonged action of this drug, a cumulative effect is possible, and with an excessive vasopressor response there may be a prolonged elevation of blood pressure even when therapy with metaraminol tartrate is discontinued.
Because of its vasoconstrictor effect, metaraminol tartrate should be given with caution in the presence of heart or thyroid disease, hypertension, or diabetes. Sympathomimetic amines may provoke a relapse in patients with a history of malaria.
When vasopressor amines are used for long periods, the resulting vasoconstriction may prevent adequate expansion of the circulating volume and may cause perpetuation of the shock state. There is evidence that plasma volume may be reduced in all types of shock, and that the measurement of central venous pressure is useful in assessing the adequacy of the circulating blood volume. Therefore, blood or plasma volume expanders should be employed when the principal reason for hypotension or shock is decreased circulating volume.
In choosing the site of injection, it is important to avoid those areas recognised as unsuitable for the use of any pressor agent, and to discontinue the infusion immediately if infiltration or thrombosis occurs. Although the urgent nature of the patient's condition may force the choice of an unsuitable injection site, the preferred areas of injection should be used when possible. The larger veins of the antecubital fossa or thigh are preferred to the veins in the ankle or the dorsum of the hand, particularly in patients with peripheral vascular disease, diabetes mellitus, Buerger's disease, or conditions with coexistent hypercoagulability.

Use in the elderly.

No data available.

Paediatric use.

The effect of therapy with metaraminol in children has not been established.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Metaraminol should be used with caution in digitalised patients, since the combination of digitalis and sympathomimetic amines is capable of causing ectopic arrhythmic activity.
MAOIs and tricyclic antidepressants have been reported to potentiate the action of sympathomimetic amines.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
There are no well controlled studies in pregnant women. Metaraminol may cause foetal hypoxia by constricting the uterine vessels thereby limiting placental perfusion. Metaraminol should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
 It is not known whether metaraminol is secreted in human milk. Because many drugs are secreted in human milk, caution should be exercised if metaraminol is given to a breastfeeding woman.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Abscess formation, tissue necrosis or sloughing rarely follow the use of metaraminol tartrate.
Sympathomimetic amines, including metaraminol tartrate, may cause sinus or ventricular tachycardia or other arrhythmias, especially in patients with myocardial infarction.

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 http://www.tga.gov.au/reporting-problems and contact Arrotex Pharmaceuticals Medical Information enquiries/Adverse Drug Reaction Reporting on 1800 195 055.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).
Overdosage may result in severe hypertension accompanied by headache, constricting sensation in the chest, nausea, vomiting, euphoria, diaphoresis, pulmonary oedema, tachycardia, bradycardia, sinus arrhythmia, atrial or ventricular arrhythmias, myocardial infarction, cardiac arrest or convulsions.
Should an excessive elevation of blood pressure occur, it may be immediately relieved by a sympatholytic agent, e.g. phentolamine. An appropriate antiarrhythmic agent may also be required.
The oral LD50 in the rat and mouse is 240 mg/kg and 99 mg/kg, respectively.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Metaraminol is a potent sympathomimetic amine that increases both systolic and diastolic blood pressure. The pressor effect begins one to two minutes after intravenous injection, about ten minutes after intramuscular injection, 5 to 20 minutes after subcutaneous injection, and lasts about 20 minutes to one hour. Metaraminol has a positive inotropic effect on the heart and has a peripheral vasoconstrictor action.
Renal, coronary, and cerebral blood flow are a function of perfusion pressure and regional resistance. In most instances of cardiogenic shock, the beneficial effect of sympathomimetic amines is attributable to their positive inotropic effect. In patients with insufficient or failing vasoconstriction, there is additional advantage to the peripheral action of metaraminol, but in most patients with shock, vasoconstriction is adequate and any further increase is unnecessary. Therefore, blood flow to vital organs may decrease with metaraminol if regional resistance increases excessively.
The pressor effect of metaraminol is decreased but not reversed by alpha-adrenergic blocking agents. A primary or secondary fall in blood pressure and a tachyphylactic response to repeated use are uncommon.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

No relevant information.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Table 2.

6.2 Incompatibilities

See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

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.

6.5 Nature and Contents of Container

5 mg/10 mL (0.5 mg/mL).

Supplied in packs of 5 x 10 mL clear glass ampoules.

10 mg/1 mL.

Supplied in packs of 5 x 1 mL clear glass ampoules.

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

Metaraminol tartrate is a white, crystalline powder, which is freely soluble in water, slightly soluble in alcohol, and practically insoluble in chloroform and in ether.

Chemical structure.


Chemical name: (1R,2S)-2-amino-1-(3-hydroxyphenyl)propan-1-ol hydrogen (2R,3R)-tartrate.
Generic name: Metaraminol tartrate.
Molecular formula: C9H13NO2.C4H6O6.
Molecular weight: 317.29.

CAS number.

33402-03-8.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes