MESTINON Tablet Ref.[8205] Active ingredients: Pyridostigmine

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.

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.

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.

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.

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. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard.

Not applicable.