PILOCARPINE HYDROCHLORIDE

Posology • For head and neck cancer patients:

The recommended initial dose for adults is 1 tablet of 5 mg three times daily. The maximal therapeutic effect is normally obtained after 4 to 8 weeks of therapy. For patients who have not responded sufficiently after 4 weeks and who tolerate the dose of 5 mg three times daily, doses of up to a maximum of 30 mg daily may be considered.

However, higher daily doses are probably accompanied by an increase in drug-related adverse effects. Therapy should be discontinued if no improvement in xerostomia is noted after 2 to 3 months of therapy. • For Sjögren's syndrome patients: The recommended dose for adults is one tablet of 5 mg four times daily.

For patients who have not responded sufficiently to a dosage of 5 mg four times daily and who tolerate this dosage, increasing the dose up to a maximum of 30 mg daily, divided over the day, may be considered. Therapy should be discontinued if no improvement in the symptoms of dry mouth and dry eyes is noted after 2 to 3 months.

Special Populations Use in the elderly:

There is no evidence to suggest that dosage should be different in the elderly.

Paediatric population:

The safety and efficacy of this medicinal product in the paediatric population have not been established.

Use in patients with impaired hepatic function:

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.

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Method of administration • For head and neck cancer patients:

Pilocarpine Hydrochloride 5 mg Film-coated Tablets should be taken with a glass of water during or directly after meals. The last tablet should always be taken in conjunction with the evening meal. • For Sjögren's syndrome patients: Pilocarpine Hydrochloride 5 mg Film-coated Tablets should be taken with a glass of water at mealtimes and bedtime.

Most of the adverse experiences observed during Pilocarpine treatment were a consequence of exaggerated parasympathetic stimulation. These adverse experiences were dose-dependent and usually mild and self-limited. However, severe adverse experiences might occasionally occur and therefore careful monitoring of the patient is recommended.

In controlled clinical trials the following adverse reactions were observed:

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, < 1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).

Nervous system disorders Very common: headache Common: dizziness Eye disorders Common: lacrimation; blurred vision; abnormal vision; conjunctivitis; eye pain Cardiac disorders Common: flushing (vasodilatation); hypertension; palpitations Respiratory, thoracic and mediastinal disorders Common: rhinitis Gastrointestinal disorders Common: dyspepsia; diarrhoea; abdominal pain; nausea, vomiting; constipation, increased salivation Uncommon: flatulence Skin and subcutaneous tissue disorders Very common: sweating Common: allergic reactions, including rash, pruritus Renal and urinary disorders Very common: increased urinary frequency Uncommon: urinary urgency General disorders and administration site conditions Very common: flu syndrome Common: asthenia, chills There is no indication of a difference between older and younger patients receiving Pilocarpine as regards reporting adverse experiences, except for dizziness, which was reported significantly more often by patients aged over 65 years.

The following adverse effects, which are due to the intrinsic pharmacological properties of pilocarpine, have been published in the medical literature: respiratory distress, gastro-intestinal spasm, atrioventricular block, tachycardia, bradycardia, cardiac arrhythmia, hypotension, shock, tremors, and mental status changes including memory loss, hallucinations, lability of affect, confusion, agitation.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. ukyellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Caution should be exercised in patients who are known or expected to sweat excessively and who cannot drink enough liquids, since dehydration could develop. Pilocarpine has been reported to increase airway resistance in asthmatic patients.

Also, patients with significant cardiovascular disease may be unable to compensate for transient changes in haemodynamics or heart rhythm induced by pilocarpine. Therefore, Pilocarpine should be administered to patients with controlled asthma or significant cardiovascular disease only if the benefits are believed to outweigh the risks, and under close medical supervision.

Pilocarpine should be used with caution in patients with the following illnesses/pathologies: - 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.

- 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. - Peptic ulceration, due to the risk of increased acid secretion.

- Underlying cognitive or psychiatric disturbances. Cholinergic agonists, like pilocarpine hydrochloride, may have dose-related central nervous system effects. - Caution should be exercised when administering Pilocarpine in patients with renal insufficiency.

- Pilocarpine may increase ureteral smooth muscle tone and could theoretically precipitate renal colic (or “ureteral reflux”), particularly in patients with nephrolithiasis. - Pilocarpine should be administered with caution in patients with narrow-angle glaucoma.

1. Pilocarpine is contraindicated in patients with clinically significant, uncontrolled cardiorenal disease, uncontrolled asthma and other chronic disease at risk for cholinergic agonists. Pilocarpine is contraindicated in cases where miosis is undesirable, such as in acute iritis.