Mestinon 10 mg or 60 mg Tablets

Myasthenia gravis.

Posology

Adults: 1-3 60 mg tablets two to four times daily, or higher doses if required. Children: 7 mg/kg body-mass daily at four hourly intervals. It is important to remember that the dosage must be individually titrated. No response to a specific dosage could be due to underdosage or overdosage. Usually in the case of too large a dose given too frequently, side effects of the muscarinic and/or nicotinic type will manifest (see section 4.8).

Method of administration

For oral use.

• Hypersensitivity to the active substance pyridostigmine and to bromides or to any of the excipients listed in section 6.1.
• MESTINON u00ae is contraindicated in mechanical intestinal or urinary obstruction.

• Although failure of patients to show clinical improvement may reflect underdosage, it can also be indicative of overdosage. Overdosage may result in cholinergic crisis, a state characterised by increasing muscle which, through involvement of the muscles of respiration, may lead to death.
• Myasthenic crisis due to an increase in the severity of the disease is also accompanied by extreme muscle weakness, and thus may be difficult to distinguish from cholinergic crisis on a symptomatic basis. Differential diagnosis can be aided by the Tensilon (edrophonium chloride) test. If 0,1 ml (1 mg) or at most 0.2 ml (2 mg) of Tensilon (edrophonium chloride) is given intravenously, a marked improvement indicates myasthenic crisis. Any other response, whether equivocal or exacerbation of symptoms, must be considered to be cholinergic. The treatment of the two conditions obviously differs radically. Whereas the presence of myasthenic crisis suggests the need for more intensive anticholinesterase therapy, the diagnosis of cholinergic crisis calls for the prompt withdrawal of all medicines of this type and institution of appropriate supportive measures, including respiratory assistance. The immediate use of atropine in cholinergic crisis is also recommended. Atropine may also be used to abolish or obtund gastrointestinal side effects or other muscarinic reactions. Care should be observed in the use of atropine for counteracting side effects; such use, by masking signs of overdosage, can lead to inadvertent induction of cholinergic crisis.
• Differentiation of myasthenic and cholinergic crisis:
• The patient with myasthenic crisis will often have a history of intervening infection, emotional trauma, perhaps a relationship to the menstrual cycle or cessation of medication. The usual dose of the medicine becomes ineffective and increased weakness or side reactions do not occur after taking medication.
• A cholinergic crisis may begin in a similar manner but the patient keeps increasing the amount and frequency of medication, with less effect and more side reactions, especially increased secretions with gastrointestinal activity. The patient in cholinergic crisis is weak, as in myasthenic crisis, but there is usually pallor (a cold clammy skin) often accompanied by hypertension, bradycardia, miosis, excessive salivation and perspiration and muscular fasciculation.
• 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 medicine dosage effect.
• Extreme caution is required when administering MESTINON u00ae to patients with obstructive respiratory diseases like bronchial asthma and chronic obstructive pulmonary diseases (COPD).
• Care should 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
• Parkinsonism
• Hyperthyroidism
• Renal impairment:
• When relatively large doses of MESTINON u00ae are taken by myasthenic patients it may be necessary to give atropine or other anti-cholinergic medicines to specifically counteract the muscarinic effects of MESTINON u00ae while maintaining its nicotinergic effect.
• MESTINON u00ae should be given with caution to elderly patients and to patients with pre-existing conduction disturbances.
• Safety in pregnancy has not been established.
• Note: certain antibiotics, especially neomycin, streptomycin and kanamycin have a mild definite non-depolarizing blocking action which may accentuate neuromuscular block. These antibiotics should only be used in the myasthenic patient when definitely indicated and then with careful observation to adjust anticholinesterase dosage.
• Lactose/Sucrose warning:
• Mestinon 10 mg Lactose warning: MESTINON 10 mg contains lactose that may have an effect on the glycaemic control of patients with diabetes mellitus. Patients with rare hereditary problems of galactose intolerance e.g. galactosaemia, the Lapp lactase deficiency or glucose-galactose malabsorption should not take MESTINON 10 mg.
• Mestinon 60 mg Sucrose warning: MESTINON 60 mg contains sucrose that may have an effect on the glycaemic control of patients with diabetes mellitus. Patients with rare hereditary conditions such as fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take MESTINON 60 mg.

• Immunosuppressant drugs medicines: The requirement for MESTINON u00ae may be decreased by concomitant use when additional therapy (corticosteroids or immune-suppressant medicines) is given. Nevertheless, a new addition of corticosteroids may initially aggravate the symptoms of myasthenia gravis.
• Thymectomy: The need for MESTINON dosing may be decreased after thymectomy.
• Methylcellulose: Methycellulose and medicines containing methycellulose as excipients can completely inhibit absorption of pyridostigmine bromide as contained in MESTINON u00ae .
• Antimuscarinics: Atropine and hyoscine antagonise the muscarinic effects of MESTINON u00ae . It should be noted that the slower gastrointestinal motility caused by these medicines may affect the absorption of MESTINON u00ae .
• Muscle relaxants: MESTINON u00ae antagonises the effect of non-polarising muscle relaxants e.g. pancuronium and vecuronium). MESTINON u00ae may prolong the effect of depolarising muscle relaxants (e.g. suxamethonium).
• Others: Aminoglycoside antibiotics, local and some general anaesthetics, antiarrhythmic medicines, and other medicines that interfere with neuromuscular transmission may interact with MESTINON.

Pregnancy

The safety of MESTINON u00ae during pregnancy has not been established.

Breastfeeding

The safety of MESTINON u00ae during breastfeeding has not been established.

MESTINON u00ae may cause miosis and accommodation disorders and an inadequate treatment of myasthenia gravis may impair visual acuity and may have minor influence on mental and/or physical abilities to perform or execute tasks or activities requiring mental alertness, judgment and/or sound coordination and vision.

Summary of the safety profile

• Nicotinic side effects are comprised chiefly of muscle cramps, fasciculation and weakness. Skin rash may occur.
• As with all cholinergic products, MESTINON u00ae may have unwanted functional effects on the autonomic nervous system.
• Muscarinic-like adverse effects may be exhibited as nausea, vomiting, diarrhoea, abdominal cramps, increased peristaltic and increased bronchial secretion, salivation, bradycardia and miosis and diaphoresis.

Within the system organ classes, adverse reactions are listed under headings of frequency (number of patients expected to experience the reaction), using the following categories:

Very common (u22651/10) Common (u22651/100 to <1/10) Uncommon (u22651/1,000 to < 1/100) Rare (u2265 1/10,000 to < 1/1,000) Very rare (< 1/10,000) Frequency not known (cannot be estimated from the available data).

Tabulated list of adverse reactions

Body System Rare Frequency not known

• Immune system disorders: hypersensitivity ( see section 4.3 )
• Nervous system disorders: syncope
• Eye disorders: miosis, increased lacrimation, accommodation disorders (e.g. blurred vision)
• Cardiac disorders: dysrhythmia (incl. bradycardia, tachycardia, AV block) as well as syncope and hypotension, Prinz metal angina
• Vascular disorders: flushing, hypotension
• Respiratory, thoracic and mediastinal disorders: increased bronchial secretion combined with bronchoconstriction
• Gastrointestinal disorders: nausea, vomiting, diarrhoea, gastrointestinal (GI) hypermotility, salivary hypersecretion, abdominal symptoms (e.g. discomfort, pain, cramps)
• Skin and subcutaneous tissue disorders: rash (disappears usually soon after ceasing of medication. Bromide containing medicines should no longer be used) hyperhidrosis, urticarial
• Musculoskeletal, connective tissue and bone disorders: increased muscle weakness, fasciculation (muscle twitching), tremors and muscle cramps or muscle hypotonia ( see section 4.9 ).
• Renal and urinary disorders: urinary urgency

Because these symptoms may be an indication of cholinergic crisis, the doctor 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 medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions to SAHPRA via the u201cReport Drug Reaction Processu201d, found online under SAHPRAu2019s safety publications: https://www.sahpra.org.za/

In the event of an overdose, side effects can be precipitated and/or be of increased severity ( see section 4.8).

• As MESTINON u00ae is excreted mainly by the kidneys, caution is advised in cases of renal function impairment.
• Overdosage may lead to u201ccholinergic crisisu201d. The signs and symptoms of overdosage are due to muscarinic and nicotinic actions. Cardiovascular and respiratory failure may occur.
• Its muscarinic effects consist of abdominal cramps, increased peristalsis, diarrhoea, nausea and vomiting, increased bronchial secretions, salivation, hyperhidrosis and miosis.
• Nicotinic increased effects are muscular cramps, fasciculations and general weakness up to paralysis, which may produce apnoea and cerebral anoxia in particularly severe cases.
• Bradycardia ranging up to cardiac arrest, hypotension ranging up to cardiovascular collapse may occur if overdosage is excessive.
• Central nervous system effects may include agitation, confusion, slurred speech, nervousness, irritation, visual hallucinations, dysarthria, convulsions and coma.
• Skin rashes due to sensitivity to bromide ion have been reported.
• Overdosage with decreased therapeutic effect must be differentiated from myasthenia gravis.

Suggested treatment of overdosage:

• MESTINON u00ae treatment must be stopped immediately.
• Artificial ventilation should be instituted if respiration is severely depressed.
• The muscarinic effects are the most serious and may be controlled by atropine.
• Nicotinic effects may be treated symptomatically.