PARACODIN Tablet Ref.[49814] Active ingredients: Dihydrocodeine

As dihydrocodeine may bring about histamine release, Paracodin Tablets should not be given during an attack of asthma and should be administered with due care to persons liable to such attacks.

Dosage should be reduced in the elderly and in patients with hypothyroidism, chronic hepatic disease or renal insufficiency.

Prolonged regular use of high dosage, except under medical supervision, may lead to physical and psychological dependence (addiction) and result in withdrawal symptoms such as restlessness and irritability, once the drug is stopped.

Patients with pre-existing seizure disorders should be observed with caution when prescribed this product.

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

CYP2D6 Metabolism

Dihydrocodeine is a semi-synthetic analogue of codeine. There are similarities between the metabolism of codeine and dihydrocodeine in the formation of (0-demethylated) metabolites catalysed by CYP2D6. There are genetic differences in the expression of the CYP2D6 enzyme. For codeine, this results in a risk of lack of efficacy in poor metabolisers and a risk of opioid toxicity in patients who are ultra rapid metabolisers. The clinical implications of CYP2D6 genetic polymorphisms have not been sufficiently elucidated for dihydrocodeine (see section 5.2).

As with all other drugs acting on the central nervous system, the consumption of alcohol should be avoided under Paracodin therapy.

Paracodin should not be administered to patients who are receiving monoamine oxidase inhibitors or who have received these within the previous 14 days.

As occurs for other opoids, the effects of DHC on the central nervous system may be enhanced by other drugs acting on the central nervous system such as:

• Anxiolytics or hypnotics may increase CNS depression, particularly respiratory depression
• Triciclic antidepressants (e.g. imipramine, amitriptyline) may enhance CNS depressive effects when taken with dihydrocodeine
• Antipsychotic may enhance hypotensive and sedative effects.

The efficacy of analgesics is enhanced.

Cimetidine and other drugs (e.g. quinidine, fluoxetine) may inhibit hepatic metabolism of dihydrocodeine but no change of the clinical effects of dihydrocodeine have been noted.

All narcotic analgesics can cross the placenta and are also excreted in breast milk. They should not be used during pregnancy or lactation unless considered essential by the physician.

Paracodin Tablets may induce drowsiness. Patients receiving Paracodin Tablets should not drive or operate machinery unless it has been shown not to affect physical or mental ability.

At the usual recommended doses the most frequent side effects are nausea and constipation and less frequently headache and dizziness.

Psychiatric disorders: Confusion, euphoria.

Nervous system disorders: Dizziness, headache, vertigo or drowsiness.

Eye disorders: Miosis, visual disturbances.

Respiratory, thoracic and mediastinal disorders: Dyspnea, respiratory depression may occur at larger doses. Laringeal edema has been reported very rarely.

Gastrointestinal disorders: Nausea, vomiting, gastrointestinal complaints and constipation.

Cardiovascular disorders: Bradycardia, hypotension, palpitations, facial flushing.

Skin and subcutaneous tissue disorders: Rash, urticaria, pruritus. Angioedema (Quinke’s edema).

Renal and urinary disorders: Urinary retention.

General disorders and administration site conditions: Fatigue.

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. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL-Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517, Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

Not applicable.