1. Name of the medicinal product

Pyridostigmine bromide Tablets USP 60mg Taj Pharma

2. Qualitative and quantitative composition

Each tablet contains 60 mg pyridostigmine bromide.

For the full list of excipients, see section 6.1

3. Pharmaceutical form

Tablet for oral administration.

4. Clinical particulars

4.1 Therapeutic indications

Myasthenia gravis, paralytic ileus and post-operative urinary retention.

4.2 Posology and method of administration

Posology

Myasthenia gravis

Adults

Doses of 30 to 120mg are given at intervals throughout the day when maximum strength is needed (for example, on rising and before mealtimes). The usual duration of action of a dose is 3 to 4 hours in the daytime but a longer effect (6 hours) is often obtained with a dose taken on retiring for bed.

The total daily dose is usually in the range of 5 – 20 tablets but doses higher than these may be needed by some patients.

Paediatric population

Children under 6 years old should receive an initial dose of half a tablet (30mg) of Mestinon; children 6 – 12 years old should receive one tablet (60mg). Dosage should be increased gradually, in increments of 15 – 30mg daily, until maximum improvement is obtained. Total daily requirements are usually in the range to 30 – 360mg.

Other Indications (paralytic ileus, post-operative urinary retention)

Adults

The usual dose is 1 to 4 tablets (60 – 240mg) per day.

Paediatric population

The usual dose is 15 – 60mg per day.

The frequency of these doses may be varied according to the needs of the patient.

Special populations

Elderly

There are no specific dosage recommendations for Mestinon in elderly patients.

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.

Hepatic impairment

There are no specific dosage recommendations for Mestinon in patients with hepatic impairment.

Method of administration

For oral use

4.3 Contraindications

Mestinon is contra-indicated in patients with:

– Hypersensitivity to the active substance, bromides or to any of the excipients listed in section 6.1.

– Mechanical gastro-intestinal or urinary obstruction

4.4 Special warnings and precautions for use

Extreme caution is required when administering Mestinon to patients with obstructive respiratory diseases like bronchial asthma and chronic obstructive pulmonary disease (COPD).

Care should also be taken in patients with:

– Arrhythmias such as bradycardia and AV block(elderly patients may be more susceptible to dysrhythmias than the young adult)

– Recent coronary occlusion

– Hypotension,

– Vagotonia

– Peptic ulcer

– Epilepsy or Parkinsonism

– Hyperthyroidism

When relatively large doses of Mestinon are taken by myasthenic patients it may be necessary to give atropine or other anticholinergic drugs to counteract the muscarinic effects. It should be noted that the slower gastro-intestinal motility caused by these drugs may affect the absorption of Mestinon.

In all patients the possibility of “cholinergic crisis”, due to overdosage of Mestinon , and its differentiation from “myasthenic crisis”, due to increased severity of the disease, must be borne in mind. Both types of crisis are manifested by increased muscle weakness, but whereas myasthenic crisis may require more intensive anticholinesterase treatment, cholinergic crisis calls for immediate discontinuation of this treatment and institution of appropriate supportive measures, including respiratory assistance.

The requirement for Mestinon is usually markedly decreased after thymectomy or when additional therapy (steroids, immunosuppressant drugs) is given.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

Immunosuppressant drugs

The requirement for pyridostigmine bromide could be decreased when additional therapy (steroids, immunosuppressant drugs) is given although peak plasma concentration and AUC of pyridostigmine may decrease by high doses of corticosteroids.

Methylcellulose

Methylcellulose and medicine containing methylcellulose as excipients can completely inhibit absorption of pyridostigmine bromide.

Antimuscarinics

Atropine and hyoscine antagonise the muscarinic effects of pyridostigmine bromide. It should be noted that the slower gastro-intestinal motility caused by these drugs may affect the absorption of pyridostigmine bromide.

Muscle Relaxants

Pyridostigmine antagonises the effect of non-depolarising muscle relaxants (e.g. pancuronium and vecuronium). Pyridostigmine may prolong the effect of depolarising muscle relaxants (e.g. suxamethonium).

Others

Aminoglycoside antibiotics, local and some general anesthetics, antiarrhythmic agents, and other drugs that interfere with neuromuscular transmission may interact with pyridostigmine bromide.

4.6 Fertility, pregnancy and lactation

The safety of Mestinon during pregnancy or lactation has not been established.

Although the possible hazards to mother and child must be weighed against the potential benefits in every case, experience with Mestinon in pregnant patients with myasthenia gravis has revealed no untoward effect of the drug on the course of pregnancy.

Pyridostigmine bromide crosses the placenta barrier. Excessive doses of pyridostigmine bromide should be avoided; the newborn child should be monitored for possible effects.

Intravenous application of pyridostigmine bromide can induce contraction of the uterus (especially in the last period of pregnancy).

As the severity of myasthenia gravis often fluctuates considerably, particular care is required to avoid cholinergic crisis, due to overdosage of the drug, but otherwise management is no different from that in non-pregnant patients.

Observations indicate that only negligible amounts of Mestinon are excreted in breast milk; nevertheless, due regard should be paid to possible effects on the breast-feeding infant.

4.7 Effects on ability to drive and use machines

Due to miosis and accommodation disorders caused by pyridostigmine bromide or an inadequate treatment of Myasthenia gravis, Mestinon may impair visual acuity and consequently the ability to react as well as the ability to drive and use machines.

4.8 Undesirable effects

As with all cholinergic products, Mestinon may have unwanted functional effects on

the autonomic nervous system. Muscarine-like adverse effects may be exhibited as nausea, vomiting, diarrhoea, abdominal cramps, increased peristaltic and increased bronchial secretion, salivation, bradycardia and miosis.

The primary nicotinic effects are muscle spasms, fasciculation and muscular weakness.

Adverse reactions are listed below according to system organ class and frequency. Frequencies are defined according to the following convention:

Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000) Very rare (<1/10,000) Not known (cannot be estimated from the available data)

Eye disorders

Frequency not known: Miosis, increased lacrimation, accommodation disorders

Cardiac disorders

Frequency not known: Arrhythmia (including bradycardia, tachycardia, AV block), as well as syncope and hypotension (see section 4.9)

Respiratory, thoracic and mediastinal disorders

Frequency not known: Increased bronchial secretion combined with bronchoconstriction

Gastrointestinal disorders

Frequency not known: Nausea, vomiting, diarrhoea, abdominal cramps, gastrointestinal hypermotility, salivary hypersecretion

Skin and subcutaneous tissue disorders

Frequency not known: Rash (disappears usually soon after ceasing of medication. Bromide containing medicines should no longer be used.) Hyperhydrosis

Musculoskeletal and connective tissue disorders

Frequency not known: Increased muscle weakness fasciculation, tremors and muscle cramps or muscle hypotonia (see section 4.9)

Renal and urinary disorders

Frequency not known: Urinary urgency

Because these symptoms may be an indication of cholinergic crisis, the physician should be notified immediately to clarify the diagnosis (see section 4.9)

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important.

4.9 Overdose

Overdosage may lead to “cholinergic crisis” characterised by severe muscarinic and nicotinic symptoms of marked muscle weakness. Cardiovascular and respiratory failure may occur.

Signs of overdosage due to muscarinic effects may include abdominal cramps, increased peristalsis, diarrhoea, nausea and vomiting, increased bronchial secretions, salivation, hyperhydrosis and miosis. Nicotinic effects consist of muscular cramps, fasciculations and general weakness up to paralysis.

Hypotension up to cardiovascular collapse, bradyarrhythmia, up to cardiac arrest may also occur.

Central nervous system effects may include agitation, confusion, slurred speech, nervousness, irritation, visual hallucinations.

Artificial ventilation should be instituted if respiration is severely depressed.

Atropine sulphate 1 to 2mg intravenously is an antidote to the muscarinic effects. Doses may be repeated every 5 to 30 minutes as needed.

5. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Nervous system, parasympathomimetics, anticholinesterases, pyridostigmine ,

Mestinon is an antagonist to cholinesterase, the enzyme which normally destroys acetylcholine. The action of Mestinon can briefly be described, therefore, as the potentiation of naturally occurring acetylcholine. Mestinon has a more prolonged action than Prostigmin (neostigmine) although it is somewhat slower to take effect (generally taking 30 – 60 minutes). Because it has a weaker “muscarinic” action than Prostigmin, it is usually much better tolerated by myasthenic patients in whom the longer action is also an advantage.

5.2 Pharmacokinetic properties

Oral pyridostigmine bromide is poorly absorbed. Maximum plasma concentrations occur at 1 to 2 hours and it is eliminated by the kidney largely unchanged with a half-life of 3 to 4 hours.

5.3 Preclinical safety data

There are no preclinical data of relevance to the prescriber, which are additional to those already included in other sections of the SmPC.

6. Pharmaceutical particulars

6.1 List of excipients

Each tablet contains:

Lactose, Starch, Precipitated Silica, Talc, Magnesium Stearate, Purified Water

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

Store below 25°C. Store in the original package in order to protect from light and moisture.

6.5 Nature and contents of container

Amber glass bottles with aluminum screw or low-density polyethylene caps and desiccant containing 200 tablets.

6.6 Special precautions for disposal and other handling

No special requirements for disposal.

7. Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Pyridostigmine bromide Tablets USP 60mg Taj Pharma

Please read all of this leaflet carefully before you start taking this medicine.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you.

Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

If you experience any side effect and this becomes serious, tell your doctor or pharmacist.

In this leaflet:

1. What Pyridostigmine bromide Tablet is and what it is used for
2. Before you take Pyridostigmine bromide Tablet
3. How to take Pyridostigmine bromide Tablets
4. Possible side effects
5. How to store Pyridostigmine bromide Tablets
6. Further information

 

1. What pyridostigmine bromide tablet is and what it is used for

Pyridostigmine bromide Tablet is used for the treatment of myasthenia gravis. In patients who suffer from myasthenia gravis the muscles quickly become tired and weak and,

in severe cases, the muscles may become paralysed.

Myasthenia gravis is caused by excessive activity in the body of a protein called cholinesterase.

Pyridostigmine bromide Tablet belongs to a group of medicines known as cholinesterase inhibitors. Cholinesterase inhibitors stop the excessive activity of cholinesterase and in this way, help muscles to work properly.

Pyridostigmine bromide Tablet is also used to treat some rare forms of constipation (paralytic ileus) and inability to pass urine after an operation.

2. Before you take pyridostigmine bromide tablet tablets

Do not take Pyridostigmine bromide Tablet Tablets if you:

• Are allergic (hypersensitive) to pyridostigmine, bromides or any of the other ingredients of Pyridostigmine bromide Tablet Tablets (these are listed in section 6, ˝Further Information˝).
• Are constipated or cannot urinate, unless your doctor has told you to use this medicine. This is because Pyridostigmine bromide Tablet is only for some types of consti- pation and inability to pass urine (see Section 1).

Take special care with Pyridostigmine bromide Tablet

Before treatment with Pyridostigmine bromide Tablet, tell your doctor if you:

• Suffer from asthma or have other chest problems such as wheeziness, difficulty in breathing or chronic cough.
• Have recently had coronary obstruction (heart attack), have a slow heart beat or any other heart condition.
• Have low blood pressure.
• Have a stomach ulcer.
• Have epilepsy.
• Have Parkinson’s disease.
• Have kidney problems.
• Suffer from a condition called vagotonia (this is a condition where overactivity of the vagus nerve causes symptoms such as slow heart rate, low blood pressure, constipation, sweating and painful muscle spasms).
• Have an overactive thyroid gland
• Have had an operation to remove your thymus gland.
• There is no evidence to suggest that Pyridostigmine bromide Tablet has any special effects on elderly patients.
• Taking other medicines
• Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
• This is extremely important, as using more than one medicine at the same time can strengthen or weaken the effect of the medicines. In particular, tell your doctor if you are taking any of the following medicines:
• Medicines known as steroids or other immunosuppressant medicines.
• Medicines known as antimuscarinics (e.g. atropine, hyoscine).
• Medicines containing methylcellulose
• Antibiotics
• Medicines to treat an irregular heart beat
• Other medicines that interfere with transmission between nerves and muscles
• If you are going to have surgery
• Tell your doctor that you are taking Pyridostigmine bromide Tablet. Pyridostigmine bromide Tablet can stop the effect of some medicines used to relax muscles during surgery (e.g. pancuronium, vencuronium).
• Pyridostigmine bromide Tablet can also prolong the effect of other muscle relaxants (e.g. suxamethonium).
• Pregnancy and breast-feeding
• Tell your doctor before you start treatment if you:
• Are pregnant, if you think you are pregnant, or if you intend to become pregnant.
• Are breast-feeding, as Pyridostigmine bromide Tablet passes into breast milk in small amounts.
• Your doctor will then decide if you can take this medicine.
• Driving and using machines
• Pyridostigmine bromide Tablet may reduce the sharpness of your eyesight and therefore your ability to drive or use machines. Do not drive or operate machines if this medicine affects your ability to see clearly.
• Important information about some of the ingredients of Pyridostigmine bromide Tablet Tablets
• Pyridostigmine bromide Tablet Tablets contain lactose. Therefore, if you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

3. How to take pyridostigmine bromide tablet

Swallow the tablets with water or another non- alcoholic drink. If you have difficulty swallowing, you can break the tablets into pieces.

You should check with your doctor or pharmacist if you are not sure how to take Pyridostigmine bromide Tablet.

The dose will depend on your illness, your needs and on your age as follows:

For myasthenia gravis:

• The usual adult dose is 1/2 to 2 tablets (30 to 120 mg Pyridostigmine bromide Tablet) to be taken five to six times daily, or higher doses if needed, as recommended by your doctor.
• For children under 6 years, the usual dose is 1/2 a tablet (30 mg). For children aged 6 to 12 years, the usual starting dose is 1 tablet (60 mg). The doctor will then gradually increase the dose until maximum improvement is seen. In children the total dose per day is usually 30 to 360 mg.

The tablets take 30 to 60 minutes to start working after you have taken them.

The effect of each dose should last about four hours during the day and about six hours at night.

You should try to take your medicine so that it can work when your muscles are needed most, for

example, when you get up and about 30 to 60 minutes before a meal.

For paralytic ileus (constipation) and post-operative inability to pass urine:

• The usual adult dose is 1 to 4 tablets (60 to 240 mg Pyridostigmine bromide Tablet) daily and for children 1/4 to 1 tablet

(15 to 60 mg) daily, depending on the needs of the patient.

If you take more Pyridostigmine bromide Tablet than you should

If you take too many tablets or someone else accidentally takes your medicine, contact your doctor, pharmacist or nearest hospital straight away.

If you forget to take Pyridostigmine bromide Tablet

If you forget to take one of your daily doses, take it as soon as you remember, and take the next dose at the normal time. Do not take a double dose to make up for a forgotten dose. If you miss more than a single dose, you should contact your doctor for advice.

4. Possible side effects

Like all medicines, Pyridostigmine bromide Tablet can cause side effects, although not everybody gets them.

Possible side effects with Pyridostigmine bromide Tablet:

Side effects of unknown frequency:

• visual disturbance, producing more tears than usual

an irregular heartbeat, heart block, low blood pressure, fainting

• producing more phlegm than usual combined with constriction of the airways
• feeling sick, vomiting, diarrhoea, stomach cramps, producing more saliva than usual
• rash
• excessive sweating
• muscle weakness and twitching, shaking, muscle cramps
• sudden, compelling urge to urinate.

Reporting of side effects

If you get any side effects, talk to your doctor, phar- macist or nurse. This includes any possible side

effects not listed in this leaflet.

5. How to store pyridostigmine bromide tablet tablets

Keep Pyridostigmine bromide Tablet Tablets out of the reach and sight of children.

Store the bottle in the original outer carton.

Keep the bottle tightly closed in order to protect from moisture.

Do not store above 25 °C.

Do not use Pyridostigmine bromide Tablet Tablets after the expiry date which is stated on the bottle label and outer carton after the text ˝EXP˝. The expiry date refers to the last day of that month.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. Further information

What Pyridostigmine bromide Tablet contains

Active substance:  Each tablet contains 60 mg

of pyridostigmine bromide.

Other ingredients: Colloidal hydrated silica, maize

starch, lactose monohydrate, talc and magnesium stearate.

What Pyridostigmine bromide Tablet looks like and contents of the pack

The tablets are scored on one side so that they can be broken into halves or quarters and ˝ V ˝ is imprinted on the other side.

7. Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com