Pyridostigmine Bromide

Mestinon (pyridostigmine bromide)

Mestinon is available in the following forms: syrup containing 60 mg pyridostigmine bromide per teaspoonful in vehicle containing 5% alcohol, glycerin, lactic acid, sodium benzoate, sorbitol, sucrose, FD&C Red No 40, FD&C Blue No 1, flavours and water. Tablets containing 60 mg pyridostigmine bromide; each tablet also contains lactose, silicon dioxide and stearic acid. Timespan tablets containing 180 mg pyridostigmine bromide; each tablet contains carnauba wax, corn derived proteins, magnesium stearate, silica gel and tribasic calcium phosphate.

Actions: Mestinon inhibits the destruction of acetylcholine by cholinesterase and thereby permits freer transmission of nerve impulses across the neuromuscular junction. Pyridostigmine is an analog of neostigmine (Prostigmin), but differs from it in certain clinically significant respects; for example, pyridostigmine is characterized by a longer duration of action and fewer gastrointestinal side effects.

Indication: Mestinon is useful in the treatment of myasthenia gravis.

Contraindications: Mestinon is contraindicated in mechanical intestinal or urinary obstruction, and particular caution should be used in it's administration to patients with bronchial asthma. Care should be observed in the use of atropine for counteracting side effects, as discussed below.

Warnings: Although failure of patients to show clinical improvement may reflect underdosage, it can also be indicative of overdosage. As is true of all cholinergic drugs, overdosage of Mestinon may result in cholinergic crisis, a state characterized by increasing muscle weakness 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. Such differentiation is extremely important, since increases in doses of Mestinon or other drugs of this class in the presence of cholinergic crisis or of a refractory or "intensive" state could have grave consequences. Osserman and Gerkins indicate that the differential diagnosis of the two types of crisis may require the use of Tensilon (edrophonium chloride) as well as clinical judgement. 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, according to Osserman and Gerkins, calls for the prompt withdrawal of all drugs of this type. 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; but such use, by masking signs of overdosage, can lead to inadvertent induction of cholinergic crisis.

For detailed information on the management of patients with myasthenia gravis, the physician is referred to one of the excellent reviews such as those by Osserman and Gerkins, Grob or Schwab.

Usage in pregnancy: The safety of Mestinon during pregnancy or lactation in humans has not been established. Therefore, use of Mestinon in women who may become pregnant requires weighing the drugs potential benefits against its possible hazards to mother and child.

Adverse reactions: The side effects of Mestinon are most commonly related to overdosage and generally are of two varieties, muscarinic and nicotinic. Among those in the former group are nausea, vomiting, diarrhoea, abdominal cramps, increased peristalsis, increased salivation, increased bronchial secretions, miosis and diaphoresis. Nicotinic side effects are comprised chiefly of muscle cramps, fasciculation and weakness. Muscarinic side effects can usually be counteracted by atropine, but for reasons shown in the preceding section the expedient is not without danger. As with any compound containing the bromide radical, a skin rash may be seen in an occasional patient. Such reactions usually subside promptly upon discontinuance of the medication.

Dosage and administration: Mestinon is available in three dosage forms:

Syrup-raspberry flavoured - containing 60 mg pyridostigmine bromide per teaspoonful (5 mL). This form permits accurate dosage adjustment for children and "brittle" myasthenic patients who require fractions of 60 mg doses. It is more easily swallowed, especially in the morning, by patients with bulbar involvement.

Conventional tablets - each containing 60 mg pyridostigmine bromide.

Timespan tablets - each containing 180 mg of pyridostigmine bromide. This form provides uniformly slow release, hence prolonged duration of drug action; it facilitates control of myasthenic symptoms with fewer individual doses daily. The immediate effect of a 180 mg Timespan tablet is about equal to that of a 60 mg conventional tablet; however, it's duration of effectiveness, although varying in individual patients, averages 21/2 times that of a 60 mg dose.