Consumer medicine information

Mestinon

Pyridostigmine bromide

BRAND INFORMATION

Brand name

Mestinon

Active ingredient

Pyridostigmine bromide

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Mestinon.

What is in this leaflet

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

MESTINON is a prescription medicine, it should be used only under strict medical supervision.

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

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

Keep this leaflet. You may need to read it again.

What MESTINON is used for

MESTINON is used to treat myasthenia gravis. This is a condition whereby you have muscle weakness and tiredness especially on repeated use.

MESTINON belongs to a group of medicines called cholinergic antimyasthenics. It works by preventing the breakdown of a chemical called acetylcholine. This chemical is needed to stimulate muscle movement.

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.

There is not enough information to recommend the use of this medicine for children.

Before you take MESTINON

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make.

When you must not take it

Do not take MESTINON if you have an allergy to:

  • any medicine containing pyridostigmine bromide
  • any of the ingredients listed at the end of this leaflet.

Symptoms of an allergic reaction may include:

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

Do not take MESTINON if you have intestinal blockage or urinary tract blockade or urinary tract infection. This medicine may make the condition worse.

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 this medicine to children. Safety and effectiveness in children have 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

Tell your doctor if you have had any unusual or allergic reactions to

  • anticholinesterase agents like medicines used in Alzheimer's disease, ambenonium, bromides and neostigmine. Ask your doctor or pharmacist if you are not sure if you are taking any of these medicines
  • other substances such as foods, preservatives or dyes

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.

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

  • epilepsy
  • problems with your lungs such as asthma or bronchitis
  • heart problems
  • slow or irregular heart beats
  • stomach ulcer
  • kidney and thyroid problems

Tell your doctor if you are pregnant or planning to fall pregnant. Muscle weakness has occurred temporarily in some newborn babies whose mothers took antimyasthenics during pregnancy.

Tell your doctor if you are breast-feeding. It is not known whether the active ingredient in MESTINON passes into breast milk and could affect your baby.

Your doctor can advise you of the risks and benefits of taking MESTINON while you are pregnant or breast feeding.

If you have not told your doctor about any of the above, tell him/her before you start taking MESTINON.

Taking other medicines

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

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

  • muscle relaxants such as suxamethonium
  • atropine contained in medicines for travel sickness and stomach cramps, or use in surgery (injection) or used as an antidote to insecticide poisoning (tablets)
  • aminoglycoside antibiotics such as gentamicin which are used to treat bacterial infections.
  • some general and local anaesthetics
  • medicines to treat abnormal heart rhythms
  • methocarbamol, a medicine to treat muscle pain and spasms
  • dexpanthenol (not available in Australia)

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

Ask your doctor or pharmacist if you are not sure if you are taking any of these medicines. Your doctor or pharmacist will advise you.

How to take MESTINON

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 bottle, ask your doctor or pharmacist for help.

How much to take

The dose of MESTINON will be different for different patients. Follow your doctor's orders or the directions on the label. The following doses include only the average doses of these medicines. If your dose is different, do not change it unless your doctor tells you to do so.

The number of tablets you take depends on the strength of the medicine. Also, the number of doses you take each day, the interval between doses should be at least six hours, and the length of time you take the medicine depend on the medical problem for which you are taking these medicines.

The usual adult dose is one to three MESTINON 60 mg tablets two to four times daily. In severe cases, one to three MESTINON Timespan 180 mg tablets once or twice daily.

If you have difficulty in eating, your doctor will adjust your dosage so that you may need to take larger doses at times of greatest fatigue e.g. 30-45 minutes before meals.

Mestinon may not restore your muscle strength to normal and you should not increase your dose above the maximum response level in an attempt to relieve all symptoms

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

How to take it

Swallow the tablets whole with a full glass of water.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone in Australia 13 11 26; in New Zealand 03 474 7000) for advice, or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have taken too much MESTINON. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If you take too much, you are more likely to experience side effects listed in the side effects section below.

While you are using MESTINON

Things you must do

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

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

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

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

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

Things you must not do

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

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

Side effects

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

This medicine helps most people with myasthenia gravis, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical 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 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:

  • nausea and vomiting
  • diarrhoea
  • stomach cramps or pains
  • increased saliva
  • chest congestions
  • low blood pressure
  • skin rash
  • muscle cramps and twitching

The above list includes the more common side effects of your medicine. These are all mild side effects of MESTINON.

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

  • slowed heart rate
  • shortness of breath
  • severe rash
  • irritation
  • swollen face

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

After using MESTINON

Storage

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

Keep your tablets in a cool dry place where the temperature stays below 25°C.

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

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

Disposal

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

Product description

What it looks like

MESTINON 10 mg is round, biconvex, white to off-white tablet with no markings and comes in packs of 50, 100# and 250# tablets.

MESTINON 60 mg is round, biconvex, pale orange, sugar coated tablet with no markings and comes in a pack of 150s.

MESTINON Timespan 180 mg is round, biplanar, grey-yellow tablet with a marking 'VM180' on one side and scored on the other side and comes in packs of 50 and 100# tablets.

Ingredients

MESTINON 10mg contains 10 mg of pyridostigmine bromide as the active ingredient. It also contains:

  • maize starch
  • colloidal anhydrous silica
  • lactose monohydrate
  • purified talc
  • magnesium stearate
  • potato starch

MESTINON 60mg contains 60 mg of pyridostigmine bromide as the active ingredient. It also contains:

  • maize starch
  • colloidal anhydrous silica
  • purified talc
  • povidone
  • acacia
  • iron oxide red CI77491
  • iron oxide yellow CI77492
  • magnesium stearate
  • potato starch
  • liquid paraffin
  • hard paraffin
  • sucrose
  • rice starch

MESTINON Timespan 180mg contains 180 mg of pyridostigmine bromide as the active ingredient. It also contains:

  • carnauba wax
  • colloidal anhydrous silica
  • calcium phosphate
  • zein
  • magnesium stearate

Sponsor

MESTINON is distributed in Australia by:

iNova Pharmaceuticals (Australia) Pty Limited
ABN: 13 617 871 539
Level 10, 12 Help Street
Chatswood NSW 2067
Tel: 1800 630 056

Australian Registration Numbers

MESTINON 10mg - AUST R 13747

MESTINON 60mg - AUST R 13748

MESTINON Timespan 180mg - AUST R 13749

®= Registered Trademark

# - not currently distributed in Australia

This leaflet was prepared in September 2009 and updated in September 2019.

Published by MIMS December 2019

BRAND INFORMATION

Brand name

Mestinon

Active ingredient

Pyridostigmine bromide

Schedule

S4

 

1 Name of Medicine

Pyridostigmine bromide.

6.7 Physicochemical Properties

C9H13BrN2O2.
Pyridostigmine bromide is chemically described as the dimethylcarbamic ester of 1-methyl-3-hydroxypyridinium bromide. It occurs as a white or nearly white, hygroscopic, crystalline powder. It is freely soluble in alcohol and chloroform but practically insoluble in ether.

Chemical structure.


CAS number.

101-26-8.

2 Qualitative and Quantitative Composition

Mestinon contains, as active substance, pyridostigmine bromide.
Mestinon 10 mg tablets also contain the excipients lactose monohydrate, magnesium stearate, colloidal anhydrous silica, maize starch, potato starch and purified talc.
Mestinon 60 mg tablets also contain the excipients acacia, iron oxide red, iron oxide yellow, magnesium stearate, hard paraffin, liquid paraffin, povidone, colloidal anhydrous silica, maize starch, potato starch, rice starch, sucrose, and purified talc.
Mestinon Timespan 180 mg tablets also contains the excipients calcium phosphate, carnauba wax, magnesium stearate, colloidal anhydrous silica and zein.

Excipient with known effect.

Lactose monohydrate and sucrose.

3 Pharmaceutical Form

Mestinon 10 mg.

Round, biconvex, white to off-white tablet with no markings.

Mestinon 60 mg.

Round, biconvex, pale orange, sugar coated tablet with no markings.

Mestinon 180 mg.

Round, biplanar, grey-yellow tablet with a marking 'V M180' on one side and scored on the other side.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Action: Cholinergic antimyasthenic.
Mestinon possesses cholinergic properties due to competitive inhibition of cholinesterase enzyme which normally hydrolyses acetylcholine at the cholinergic synapses and neuroeffector junctions. Thus, the drug causes generalised cholinergic response including increased tone of skeletal and intestinal musculature, miosis, uterine and bronchial spasm, bradycardia, increased secretion of exocrine glands (e.g. saliva, sweat) etc. In addition, pyridostigmine has a direct cholinomimetic effect on skeletal muscle.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Duration of action.

Mestinon has a variable duration of action in patients with myasthenia gravis, depending on the physical and emotional stress suffered by the patient and the severity of the disease. After oral administration, the drug generally has an onset of action of 30-45 minutes and a duration of action of 3-6 hours.
The longer intervals between doses of Mestinon compared with neostigmine facilitate treatment in myasthenia gravis; once control has been achieved the effect persists overnight. In certain cases Mestinon may be combined with neostigmine (e.g. Mestinon during the day and in the evening, neostigmine in the morning).

Absorption.

Only about 40% of an oral dose of Mestinon is absorbed, significant amounts being destroyed in the gastrointestinal tract. The presence of permanently charged quaternary ammonium groups confers high water solubility. Thus pyridostigmine shows greatest absorption in the duodenum, but overall absorption is poor and variable.

Distribution.

Mestinon is distributed to the extracellular fluid. It does not enter the CNS. The plasma area under the curve after 4 hours is relatively constant (6,000-10,000 nanogram/mL/minute). Pyridostigmine has been reported to cross the placenta and to decrease foetal plasma cholinesterase activity after large oral doses. Following oral administration of 14C labelled pyridostigmine to animals, radioactivity was present in most tissue except brain, intestinal wall, fat and thymus.

Plasma levels.

20 to 60 nanogram/mL, despite wide dose variations.

Half-life.

1.5 to 4.25 hours oral (variable).

Metabolism.

Mestinon is extensively metabolised in the liver and 95% of metabolites are excreted in the urine. The chief metabolite is 3-hydroxy-N-methyl-pyridinium bromide. Neither pyridostigmine nor its metabolites are protein bound.

Excretion.

Excretion is by filtration and secretion, or by hepatic conversion to the glucuronide. Competition for renal transport mechanisms by tertiary amines can occur.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

Mestinon is useful in the treatment of myasthenia gravis.

4.3 Contraindications

Known hypersensitivity to anticholinesterase agents and bromide, intestinal and urinary obstruction of mechanical type.

4.4 Special Warnings and Precautions for Use

Particular caution should be used in patients with epilepsy, bronchial asthma, bradycardia, recent coronary occlusion, vagotonia, hyperthyroidism, cardiac arrhythmias, or peptic ulcer. Large oral doses of the drug should be avoided in patients with megacolon or decreased gastrointestinal motility. In these patients, the drug may accumulate and result in toxicity when gastrointestinal motility is restored.
Failure of patients to show clinical improvement may reflect overdosage or underdosage. Overdosage may result in cholinergic crisis and underdosage in myasthenic crisis. Differentiation may require the use of edrophonium. Care should be taken in counteracting side effects with atropine, as such use, by masking signs of overdosage, can lead to inadvertent induction of cholinergic crisis. In some patients, pyridostigmine bromide has a longer duration of action than the neostigmine salt. In such cases it is more likely to cause cholinergic crisis.
When pyridostigmine is used to treat myasthenia gravis, it should be kept in mind that individual muscle groups may respond differently to the same dose of an anticholinesterase agent, producing weakness in one muscle group while increasing strength in another. The muscles of the neck and of chewing and swallowing are usually the first muscles weakened by overdosage, followed by the muscles of the shoulder girdle and upper extremities, and finally the pelvic girdle, extraocular and leg muscles.
Vital capacity should be routinely measured whenever dosage is increased, so that the dosage of the anticholinesterase medication can be adjusted to ensure good respiratory function. Adequate facilities for cardiopulmonary resuscitation, cardiac monitoring, endotracheal intubation and assisting respiration should be available during dosage adjustment.

Use in renal impairment.

Mestinon is mainly excreted unchanged by the kidney. Therefore, lower doses may be required in patients with renal disease and treatment should be based on titration of drug dosage to effect.

Use in the elderly.

No data available.

Paediatric use.

Use of Mestinon is not recommended in children due to the lack of adequate clinical experience in this patient population.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Pyridostigmine does not antagonise, and may in fact prolong, the phase I block of depolarising muscle relaxants such as suxamethonium or decamethonium. Fully established phase II (desensitisation) block can be reversed by pyridostigmine, but the individual variation in transition time between phases I and II and difficulty in accurately determining the stage of depolarising neuromuscular block at any given time often make anticholinesterase administration ineffective or dangerous under these circumstances.
Atropine antagonises the muscarinic effects of pyridostigmine and this interaction is utilised to counteract the muscarinic symptoms of pyridostigmine toxicity.
Anticholinesterase agents are sometimes effective in reversing neuromuscular block induced by aminoglycoside antibiotics. However, aminoglycoside antibiotics, local and some general anaesthetics, antiarrhythmic agents, and other drugs that interfere with neuromuscular transmission should be used cautiously, if at all, in patients with myasthenia gravis, and the dose of pyridostigmine may have to be increased accordingly.
Theoretically, drugs such as dexpanthenol, which are converted to pantothenic acid in vivo, may have additive effects with pyridostigmine by increasing production of acetylcholine.
Methocarbamol, also, should be used with caution in myasthenic patients receiving pyridostigmine bromide as impaired therapeutic response has been reported.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
The maternal requirement for this drug in the context of myasthenia gravis may be absolute. Cholinergic effects in the neonate are rare.
The safety of Mestinon during pregnancy in humans has not been established.
Few data are available regarding the effects of cholinesterase inhibitors, including pyridostigmine, on the foetus because of the rarity of maternal conditions requiring the use of these drugs during pregnancy.
Transient muscular weakness has occurred in 10-20% of newborns whose mothers received anticholinesterase drugs for the treatment of myasthenia gravis, although similar symptoms have also been reported in infants whose mothers were not treated with these drugs.
The safety of Mestinon during lactation in humans has not been established.

4.8 Adverse Effects (Undesirable Effects)

Mestinon has a lower incidence of gastrointestinal stimulation and other muscarinic side effects seen with other anticholinesterases. However, nausea, vomiting, diarrhoea, abdominal cramps, increased peristalsis, increased salivation, increased bronchial secretions, myosis and diaphoresis may occur. Atropine may be used to counter these effects but not without danger, due to the difficulties in distinguishing myasthenic and cholinergic crisis.
Nicotinic effects are usually muscle cramps, fasciculation and weakness. Bradycardia and hypotension may occur. Occasionally the bromine radical may induce a rash.

Reporting suspected adverse effects.

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

4.2 Dose and Method of Administration

Myasthenia gravis.

1 to 3 tablets (60 mg) two to four times daily; more in severe cases.
1 to 3 "Timespan" tablets (180 mg) once or twice daily; the needs of individuals may vary markedly from this average, but the interval between doses should be at least six hours.
The dosage and frequency of administration depend upon the clinical response of the patient and may vary from day to day, according to remissions and exacerbations of the disease and the physical and emotional stress suffered by the patient. Dosage should be adjusted so that patients take larger doses at times of greatest fatigue, e.g. 30-45 minutes before meals in patients who have difficulty in eating.
Patients should be advised that the use of Mestinon may not restore the muscle strength to normal and should be cautioned not to increase their dose above the maximum response level in an attempt to relieve all symptoms.
Myasthenic patients may become refractory to Mestinon after prolonged treatment. Responsiveness may be restored, especially when resistance may have been caused by overdosage, by decreasing the dosage or withdrawing the drug for several days under medical supervision. High dosage of corticosteroids have also been used in intensive care facilities to increase responsiveness to anticholinesterase therapy.

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.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

Signs and symptoms of overdosage (cholinergic crisis).

Muscarinic effects (abdominal cramps, increased peristalsis, diarrhoea, nausea and vomiting, increased salivation and bronchial secretions, diaphoresis and miosis) and nicotinic actions (muscle weakness, fasciculation and cramps). Bradycardia and hypotension may occur if overdosage is excessive.
In extremely high dosage, CNS symptoms of agitation and restlessness occur and death may result from cardiac arrest, respiratory paralysis or pulmonary oedema.
In patients with myasthenia gravis, in whom overdose is most likely to occur, fasciculation and parasympathomimetic side effects may be mild or absent, making cholinergic crisis difficult to distinguish from myasthenic crisis.
The time of onset of weakness may sometimes indicate whether crisis is the result of overdosage of (or underdosage or resistance to) anticholinesterase drugs. Weakness that begins within 1 hour after drug administration is suggestive of overdosage while weakness occurring 3 or more hours after drug administration is suggestive of underdosage or resistance.
Edrophonium is generally used to distinguish cholinergic crisis from myasthenic crisis. 2 mg by intravenous injection of this short acting anticholinergic agent should cause a brief period of exacerbation of weakness in cholinergic crisis or a temporary improvement of strength in myasthenic crisis.

Suggested treatment.

Artificial respiration may be needed if respiration is markedly depressed. (Mestinon should be discontinued immediately after diagnosis is made.)
The muscarinic effects are the most serious and may be controlled by atropine (2 mg intravenously followed by intramuscular doses every 2 to 4 hours as necessary to relieve respiratory difficulty). Atropine overdosage should be avoided, as tenacious secretions and bronchial plugs may result.
It should be remembered that, unlike muscarinic effects, the skeletal muscle effects and resulting respiratory paralysis after Mestinon overdosage are not alleviated by atropine treatment.
Patients poisoned by anticholinesterases should not be given aminophylline, morphine, phenothiazine tranquillisers, reserpine, suxamethonium, theophylline or large quantities of fluids.

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

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

10 mg tablets - Store below 30°C.
60 mg tablets - Store below 25°C.
180 mg tablets - Store below 30°C

6.5 Nature and Contents of Container

Mestinon tablets are presented in coloured glass bottles in the following packs:
10 mg tablets - 50, 100# and 250's#.
60 mg tablets - 150's.
180 mg tablets - 50 and 100's#.
# Not currently distributed in Australia.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

Summary Table of Changes