MEDORPHAN Oral solution Ref.[27869] Active ingredients: Demorphan

Medorphan should not be administered to patients with chronic or persistent cough, such as occurs with asthma, or where cough is accompanied by excessive secretions, unless directed by a physician.

There have been no specific studies of Medorphan in renal or hepatic dysfunction. Due to the extensive hepatic metabolism of dextromethorphan, caution should be exercised in the presence of hepatic impairment.

Cases of dextromethorphan abuse and dependence have been reported. Caution is particularly recommended for adolescents and young adults as well as in patients with a history of drug abuse or psychoactive substances.

Dextromethorphan is metabolised by hepatic cytochrome P450 2D6. The activity of this enzyme is genetically determined. About 10% of the general population are poor metabolisers of CYP2D6. Poor metabolisers and patients with concomitant use of CYP2D6 inhibitors may experience exaggerated and/or prolonged effects of dextromethorphan. Caution should therefore be exercised in patients who are slow metabolizers of CYP2D6 or use CYP2D6 inhibitors (see also section 4.5).

Serotonin Syndrome

Serotonergic effects, including the development of a potentially life-threatening serotonin syndrome, have been reported for dextromethorphan with concomitant administration of serotonergic agents, such as selective serotonin re-uptake inhibitors (SSRIs), drugs which impair metabolism of serotonin (including monoamine oxidase inhibitors (MAOIs)) and CYP2D6 inhibitors.

Serotonin syndrome may include mental-status changes, autonomic instability, neuromuscular abnormalities, and/or gastrointestinal symptoms.

If serotonin syndrome is suspected, treatment with Medorphan should be discontinued.

Medorphan also contains sucrose, sorbitol, glucose and ethanol

MEDORPHAN contains 0.56 g of sorbitol and 0.8mg of glucose per dose. Patients with rare hereditary problems of fructose intolerance should not take this medicine.

MEDORPHAN contains 5 g of sucrose per dose. This should be taken into account in patients with diabetes mellitus.

Sucrose and glucose may be harmful to the teeth when it is used for two weeks or more.

This medicinal product also contains small amounts of ethanol (alcohol), less than 100mg per dose.

The concomitant use of a dextromethorphan-containing product and monoamine oxidase inhibitors can occasionally result in symptoms such as hyperpyrexia, hallucinations, gross excitation or coma.

CYP2D6 inhibitors

Dextromethorphan is metabolized by CYP2D6 and has an extensive first-pass metabolism. Concomitant use of potent CYP2D6 enzyme inhibitors can increase the dextromethorphan concentrations in the body to levels multifold higher than normal. This increases the patient’s risk for toxic effects of dextromethorphan (agitation, confusion, tremor, insomnia, diarrhoea and respiratory depression) and development of serotonin syndrome. Potent CYP2D6 enzyme inhibitors include fluoxetine, paroxetine, quinidine and terbinafine. In concomitant use with quinidine, plasma concentrations of dextromethorphan have increased up to 20-fold, which has increased the CNS adverse effects of the agent. Amiodarone, flecainide and propafenone, sertraline, bupropion, methadone, cinacalcet, haloperidol, perphenazine and thioridazine also have similar effects on the metabolism of dextromethorphan. If concomitant use of CYP2D6 inhibitors and dextromethorphan is necessary, the patient should be monitored and the dextromethorphan dose may need to be reduced.

Although dextromethorphan has been in widespread use for many years without apparent ill consequence, there is insufficient information on the effects of administration during human pregnancy. In addition, it is not known whether dextromethorphan or its metabolites are excreted in breast milk.

Medorphan should therefore only be used when the potential benefit of treatment to the mother exceeds any possible hazards to the developing foetus or suckling infant.

Unlikely to produce an effect.

Side effects attributed to dextromethorphan are uncommon; occasionally dizziness, nausea, vomiting, or gastro-intestinal disturbance may occur.

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 to Pharmaceutical Services, Ministry of Health, CY-1475, www.moh.gov.cy/phs, Fax: +357 22608649.

None known.