Mestinon

Mestinon

pyridostigmine bromide

Manufacturer:

A. Menarini

Distributor:

Zuellig
Full Prescribing Info
Contents
Pyridostigmine bromide.
Action
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 (t½). 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 t½ 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.
Indications/Uses
Treatment of myasthenia gravis, intestinal atony constipation, paroxysmal tachycardia & sinus tachycardia.
Dosage/Direction for Use
Adult: 1-3 dragees (60-180 mg) 2-4 times daily or higher doses if required. The total daily dose is usually in the range of 5-20 dragees (300-1200 mg) but doses higher than these may be needed by some patients.
Children 6-12 years: 1 dragee (60 mg); <6 years: Initial Dose: ½ dragee (30 mg). Dosage should increase gradually, in increments of 15-30 mg daily, until maximum improvement is obtained. Total daily requirements are usually in the range of 30-360 mg.
Administration: When using Mestinon, it is important to remember that the full effect appears gradually, usually within 15-30 min.
Patients with swallowing difficulties can take tablets broken into small pieces, instead of dragees.
In myasthenia gravis, 1 dose is effective for approximately 4 hrs during the day, while at night (owing to reduced physical activity), a longer duration of effect of around 6 hrs can be expected.
It is recommended that the times of administration be chosen so the maximum effect coincides with the most strenuous physical exertion eg, when getting up and at meal times.
Special Dosage Instructions: When used in pediatrics, the required dosage must be carefully titrated.
In case of neonatal myasthenia, generally, 1 treatment with neostigmine is preferred. However, if this appears unsuitable due to excessively cholinergic side effects, then Mestinon can be administered. In these cases, the following serves as a rough guideline: 5-10 mg by mouth in tablet form, 30-60 min before food.
Treatment over the 8th week of life is required only in extremely rare cases of congenital and familial infantile myasthenia.
Overdosage
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.
Contraindications
Mechanical obstruction of the intestinal or urinary tract and known allergy to Mestinon. Mestinon is not to be given in combination with depolarizing muscle relaxants eg, suxamethonium.
Warnings
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.
Special Precautions
Renal Impairment: Pyridostigmine 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 drug dosage to effect.
Use in Pregnancy & Lactation: 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.
Use In Pregnancy & Lactation
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.
Adverse Reactions
Like all cholinergic drugs, Mestinon can have undesirable functional effects on the autonomic nervous system.
Muscarinic-type side effects can manifest themselves as nausea, vomiting, diarrhea, stomach cramps, increased peristalsis and bronchial secretion, salivation and lacrimation, as well as bradycardia and miosis. Nicotine-type side effects consist mainly of muscle spasms, muscle twitches and muscle weakness.
Like other bromine-containing drugs, Mestinon can occasionally cause skin rash, though this generally disappears rapidly after medication has been discontinued. Further use of Mestinon or other bromine-containing preparations is then contraindicated.
Drug Interactions
Pyridostigmine antagonizes the action of curare-like nondepolarizing muscle relaxants. Atropine counteracts the cholinergic effects of pyridostigmine.
Storage
Store at a temperature not exceeding 30°C.
ATC Classification
N07AA02 - pyridostigmine ; Belongs to the class of anticholinesterase. Used as parasympathomimetics.
Presentation/Packing
Dragee 60 mg x 150's.
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