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 pyridostigmine bromide 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 pyridostigmine bromide or other drugs of this class in the presence of cholinergic crisis or of a refractory or "insensitive" state could have grave consequences. Osserman and Genkins1 indicate that the differential diagnosis of the two types of crisis may require the use of Tensilon® (edrophonium chloride) as well as clinical judgment. 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 Genkins,1 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 Genkins,2 Grob3 or Schwab.4,5
Pyridostigmine is mainly excreted unchanged by the kidney.6,7,8 Therefore, lower doses may be required in patients with renal disease, and treatment should be based on titration of drug dosage to effect.6,7
The safety of pyridostigmine bromide during pregnancy or lactation in humans has not been established. Therefore, use of pyridostigmine bromide in women who may become pregnant requires weighing the drug's potential benefits against its possible hazards to mother and child.
Safety and effectiveness in pediatric patients have not been established.