MESTINON Pyridostigmine Bromide 60mg Tablet 1's

Symptoms: Overdosage of Mestinon and other cholinesterase inhibitors can lead to cholinergic crises that manifest themselves in, among other things, pronounced muscle weakness (or exacerbated muscle weakness in patients with myasthenia gravis).
If such a situation is overlooked, life is endangered due to paralysis of the respiratory muscles. Bradycardia and, paradoxically, tachycardia are other possible effects.
Treatment: Countermeasures are the immediate withdrawal of Mestinon or other cholinergics and the slow IV administration of 1-2 mg atropine sulfate. Depending on the pulse rate, the dose is to be repeated at intervals of 2-4 hrs if required.

Although failure of patients to show clinical improvement may reflect under dosage, 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 from symptomatic basis. Such differentiation is extremely important since increases in dose of Mestinon or other drugs of this class in the presence of cholinergic crisis or of a refractory or "insensitive" state could have a grave consequence. The different diagnosis of the 2 types of crisis may require the use of Tensilon (edrophonium chloride) as well as clinical judgment.
The treatment of the 2 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 drugs of this type. The immediate use of atropine in cholinergic crisis is also recommended.
Atropine may abolish or obtund gastrointestinal side effects or other muscarinic reactions, but such use, by masking the signs of overdosage can lead to inadvertent induction of cholinergic crisis.

Reproduction studies in laboratory animals have not indicated any risk to the fetus but no controlled studies have so far been conducted in pregnant women. Therefore, Mestinon should only be used during pregnancy strictly as directed, with careful dosing and under medical supervision.
Since the possibility of pyridostigmine diffusing into breast milk cannot be ruled out, nursing mothers are advised to refrain from breastfeeding their babies during treatment.

Store at a temperature not exceeding 30°C.

Pharmacology: Properties and Effects: Pyridostigmine, the active ingredient of Mestinon, is a cholinesterase inhibitor. It is characterized by the gentle onset, smooth course, comparatively long duration and gradual decline of its cholinergic action.
Pyridostigmine has an antagonistic effect on nondepolarizing muscle relaxants only. It has a synergistic effect on depolarizing muscle relaxants.
Pharmacokinetics: Absorption: Pyridostigmine eg, other medicines of the same type, is not fully absorbed from the intestinal tract. Bioavailability following oral administration is 3-8%. Considerably higher doses are, therefore, required for oral as opposed to parenteral administration.
Distribution: Peak plasma concentrations were reached in the fasting state approximately 1.5-2 hrs after administration of pyridostigmine 120 mg. The increase in active ingredient is delayed when taken with food.
The distribution volume averages 1.4 L/kg body weight.
Pyridostigmine is not noticeably bound to plasma proteins and does not cross the blood-brain barrier.
Blood plasma levels of 20-60 ng/mL are required in order to obtain the desired therapeutic effect with myasthenia gravis.
Metabolism: Pyridostigmine is metabolized to 3-hydroxy-N-methylpyridine and other unidentified metabolites.
Elimination: Mean values of around 1.5 hrs are given for the elimination half-life (t_½). This can, however, be prolonged up to 3 times over in individual cases. Mean plasma clearance in healthy volunteers is given as 0.36-0.65 L/kg/hr. No confirmed data are available regarding the potential accumulation of unchanged pyridostigmine or active metabolites. Since the dosage must, in any case, be adjusted individually, this point is devoid of practical significance. Pyridostigmine is largely eliminated unchanged (75-81%) via the kidneys. One part (18-21%) appears as the 3-hydroxy-N-methyl-pyridine metabolite in the urine.
Other unidentified metabolites account for 1-4%.
Kinetics in Specific Clinical Situations: Impaired liver function has no relevant effect on the kinetics of pyridostigmine. The elimination t_½ can increase approximately 4-fold and plasma clearance can fall by up to around ¹/₅ in the case of age- or disease-induced kidney failure.