MEDORPHAN Syrup Ref.[27493] Active ingredients: Demorphan

This product 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.

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.

This product should not be taken with any other cough and cold medicine containing dextromethorphan.

Use of dextromethorphan with alcohol or other CNS depressants may increase the effects on the CNS and cause toxicity in relatively smaller doses.

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

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.

This product should be used with caution in atopic children due to histamine release.

Medorphan also contains also contains sucrose, sorbitol, glucose and ethanol

Medorphan contains 0.65 g of sorbitol, 3.95 g of glucose and 3.25 g of sucrose per dose.

Patients with rare hereditary problems of fructose intolerance, glucosegalactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

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

This medicinal product contains 5.03 vol % ethanol (alcohol), i.e. up to 503 mg per dose, equivalent to 10 ml beer, 4.2 ml wine per 10ml dose. Harmful for those suffering from alcoholism. To be taken into account in pregnant or breastfeeding women, children and high-risk groups such as patients with liver disease, or epilepsy.

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-free’.

Dextromethorphan should not be used concurrently in patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping treatment with MAOIs as there is a risk of serotonin syndrome (e.g. 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.

Dextromethorphan might exhibit additive CNS depressant effects when coadministered with alcohol, antihistamines, psychotropics, and other CNS depressant drugs.

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Dextromethorphan should not be used during pregnancy unless the potential benefit of treatment to the mother outweighs the possible risk to the developing foetus.

Breast-feeding

It is not known whether dextromethorphan or its metabolites are excreted in breast milk. Dextromethorphan should not be used during lactation unless the potential benefit of treatment to the mother outweighs the possible risk to the developing nursing infant.

Fertility

There are no reported effects of the use of dextromethorphan on fertility. Preclinical experience is limited (see section 5.3.).

This medicine can impair cognitive function and can affect a patient’s ability to drive safely.

Adverse drug reactions (ADRs) identified during clinical trials and postmarketing experience with dextromethorphan are included in the table below by System Organ Class (SOC). The frequencies are provided according to the following convention: 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).

ADRs are presented by frequency category based on 1) incidence in adequately designed clinical trials or epidemiology studies, if available, or 2) when incidence cannot be estimated, frequency category is listed as ‘Not known’.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions is an important way to gather more information to continuously monitor the benefit/risk balance of the medicinal product. Any suspected adverse reactions should be reported to Pharmaceutical Services, Ministry of Health, CY-1475, www.moh.gov.cy/phs, Fax: +357 22608649.

None known.