BENYLIN DRY COUGHS Syrup Ref.[7731] Active ingredients: Demorphan Diphenhydramine Menthol

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.

There have been no specific studies of this product 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.

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 this medicine should be discontinued.

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

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

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).

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

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

This product contains 6.0 vol % ethanol (alcohol), i.e. up to 240 mg per 5ml equivalent to approximately 6 ml beer, 2.5 ml wine per 5 ml. This can be harmful for those suffering from alcoholism. The ethanol content should be taken into account in pregnant or breast-feeding women, children and high-risk groups such as patients with liver disease or epilepsy.

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 co-administered with alcohol, antihistamines, psychotropics, and other CNS depressant drugs.

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

It is not known whether dextromethorphan or its metabolites are excreted in breast milk.

Unlikely to produce an effect.

This medicine can impair cognitive function and can affect a patient’s ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When taking this medicine, patients should be told:

• The medicine is likely to affect your ability to drive.
• Do not drive until you know how the medicine affects you.
• It is an offence to drive while under the influence of this medicine.
• However, you would not be committing an offence (called ‘statutory defence’) if:
  • The medicine has been taken to treat a medical or dental problem and
  • You have taken it according to the information provided with the medicine and
  • It was not affecting your ability to drive safely.

Details regarding a new driving offence concerning driving after drugs have been taken in the UK may be found here: https://www.gov.uk/drug-driving-law.

Adverse drug reactions (ADRs) identified during clinical trials and post-marketing 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 and <1/10
Uncommon ≥1/1,000 and <1/100
Rare ≥1/10,000 and <1/1,000
Very rare <1/10,000, including isolated reports
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’.

Immune System Disorders

Not known: Angioedema, Pruritus, Rash, Urticaria

Psychiatric Disorders

Not known: Insomnia, Confusional state

Nervous System Disorders

Not known: Convulsion, Dizziness, Psychomotor hyperactivity, Somnolence

Respiratory, thoracic and mediastinal Disorders

Not known: Respiratory depression

Gastrointestinal Disorders

Not known: Abdominal pain, Diarrhoea, Gastrointestinal disturbance, Nausea, Vomiting

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 the Yellow Card scheme at: www.mhra.gov.uk/yellowcard.

None known.