Pyridostigmine Other names: Pyridostigmine bromide

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.

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.

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.

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).

Aminoglycoside antibiotics, local and some general anesthetics, antiarrhythmic agents, and other drugs that interfere with neuromuscular transmission may interact with pyridostigmine bromide.

Methylcellulose and medicine containing methylcellulose as excipients can completely inhibit absorption of pyridostigmine bromide.

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

Extreme caution is required when administering pyridostigmine to patients with obstructive respiratory diseases like bronchial asthma and chronic obstructive pulmonary disease (COPD).

The safety of pyridostigmine during pregnancy has not been established. Although the possible hazards to mother and child must be weighed against the potential benefits in every case, experience with pyridostigmine in pregnant patients with myasthenia gravis has revealed no untoward effect of the drug on the course of pregnancy.

Pyridostigmine crosses the placenta barrier. Excessive doses of pyridostigmine should be avoided; the newborn child should be monitored for possible effects.

Intravenous application of pyridostigmine 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.

The safety of pyridostigmine during lactation has not been established.

Observations indicate that only negligible amounts of pyridostigmine 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 or an inadequate treatment of Myasthenia gravis, pyridostigmine 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, pyridostigmine 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

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

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.