Pilocarpine

In in vitro studies pilocarpine has been found to be an inhibitor of CYP2A6. In vivo inhibition and therefore an interaction with CYP2A6 substrates (e.g. irbesartan, coumarin) cannot be ruled out.

Pilocarpine might antagonise the anticholinergic effects of other drugs used concomitantly (e.g. atropine, inhaled ipratropium).

Patients with moderate and severe cirrhosis should start treatment on a reduced daily dosage schedule. Depending on the safety and tolerability, the dosage may gradually be increased to the normal daily dosage schedule of 5 mg three times a day.

Caution should be exercised when administering pilocarpine in patients with renal insufficiency.

Pilocarpine should be administered with caution to patients taking beta adrenergic antagonists because of the possibility of conduction disturbances.

The effects of pilocarpine may be enhanced by anticholinesterases, MAOI’s, phenothiazines, antihistamines and tricyclic antidepressants.

Concurrent administration of pilocarpine and drugs with parasympathomimetic effects is expected to result in additive pharmacologic effects.

The effects of pilocarpine on male and female fertility are not known. Studies in mice, rats and dogs have shown adverse effects on spermatogenesis. A study in rats has also indicated a possible impairment of female fertility. The safety margin for the effects on fertility is unknown.

Based on the results of available studies in animals as a precautionary meaure, pilocarpine tablets should be administered to individual human males who are attempting to father a child, only, if the expected benefit justifies potential impairment of fertility.

Pilocarpine should be used with caution in patients with peptic ulceration, due to the risk of increased acid secretion.

Pilocarpine should be used with caution in patients with known or suspected cholelithiasis or biliary tract disease. Contractions of the gallbladder or biliary smooth muscle could precipitate complications including cholecystitis, cholangitis and biliary obstruction.

Pilocarpine should be administered with caution in patients with narrow-angle glaucoma.

Pilocarpine should be used with caution in patients with chronic bronchitis and/or chronic obstructive pulmonary disease. These patients have hyperactive airways and may experience adverse effects due to increased bronchial smooth muscle tone and increased bronchial secretions.

Pilocarpine may increase ureteral smooth muscle tone and could theoretically precipitate renal colic (or “ureteral reflux”), particularly in patients with nephrolithiasis.

The safety of this medicinal product for use in human pregnancy has not been established. There are no known human data for the effects of pilocarpine on foetal survival and development. Studies in animals have shown reproductive toxicity.

Pilocarpine is not recommended during pregnancy and in women of child bearing potential not using contraception.

Animal studies have shown excretion of pilocarpine in milk at concentrations similar to those seen in plasma. It is not known whether pilocarpine is secreted in human milk. A decision must be made whether to discontinue breast-feeding or to discontinue from pilocarpine therapy.

Fertility

The effects of pilocarpine on male and female fertility are not known. Studies in mice, rats and dogs have shown adverse effects on spermatogenesis. A study in rats has also indicated a possible impairment of female fertility. The safety margin for the effects on fertility is unknown.

Based on the results of available studies in animals as a precautionary meaure, pilocarpine tablets should be administered to individual human males who are attempting to father a child, only, if the expected benefit justifies potential impairment of fertility.

Patients who experience dizziness during pilocarpine treatment should be advised not to drive or operate machinery.

Pilocarpine has been reported to cause impairment of depth perception and visual blurring. The latter may result in decreased visual acuity, especially at night and in patients with central lens changes. If this occurs, patients should be advised not to drive at night or perform hazardous activities in reduced lighting.