Benylin Dry Coughs 7.5mg/5ml Syrup
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
BENYLIN DRY COUGHS 7.5mg/5ml Syrup
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 5 ml contains:
Dextromethorphan hydrobromide 7.5 mg
Each 5ml also contains:
Sucrose 1.6g Liquid glucose 2.38g Sorbitol 325mg Ethanol 240mg
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Pale brown coloured, peach flavoured syrup.
4.1. Therapeutic indications
This product is indicated as an antitussive, for the relief of an unproductive cough.
4.2 Posology and method of administration Adults and Children aged 12 years and over:
Posology
10 ml syrup (15 mg dextromethorphan) 4 times a day.
Maximum daily dose: 40 ml syrup (60 mg dextromethorphan)
Children under 12 years:
This product is contraindicated in children under the age of 12 years (see section 4.3).
The Elderly (over 65 years)
As for adults above.
Hepatic/renal dysfunction
Due to the extensive hepatic metabolism of dextromethorphan, caution should be exercised in the presence of moderate to severe hepatic impairment (see Pharmacokinetics).
Do not exceed the stated dose.
Keep out of the sight and reach of children.
Method of Administration
For oral use
4.3 Contraindications
This product is contraindicated in individuals with known hypersensitivity to the active substance or to any of the excipients.
This product is contraindicated in individuals who are taking, or have taken, monoamine oxidase inhibitors within the preceding two weeks.
Dextromethorphan, in common with other centrally acting antitussive agents, should not be given to subjects in, or at risk of developing respiratory failure.
This product is contraindicated in patients taking serotonin reuptake inhibitors (SSRIs, see section 4.5).
Not to be used in children under the age of 12 years.
4.4 Special warnings and precautions for use
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.
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.
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.
4.5 Interactions with other medicinal products and other forms of interaction
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).
Dextromethorphan is primarily metabolised by the cytochrome P450 isoenzyme CYP2D6; the possibility of interactions with inhibitors of this enzyme, including amiodarone, haloperidol, propafenone, quinidine, SSRIs, and thioridazine, should be borne in mind.
Dextromethorphan might exhibit additive CNS depressant effects when coadministered with alcohol, antihistamines, psychotropics, and other CNS depressant drugs.
4.6 Fertility, pregnancy and lactation
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.
4.7 Effects on ability to drive and use machines
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:
o The medicine has been taken to treat a medical or dental problem and o You have taken it according to the information provided with the medicine and
o 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
4.8 Undesirable effects
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 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’.
|
Body System (SOC) |
Frequency |
Adverse Drug Reaction (Preferred Term) |
|
Immune System Disorders |
Not known Not known Not known Not known |
Angioedema Pruritus Rash Urticaria |
|
Psychiatric Disorders |
Not known Not known |
Insomnia Confusional state |
|
Nervous System Disorders |
Not known Not known Not known |
Convulsion Dizziness Psychomotor hyperactivity |
|
Not known |
Somnolence | |
|
Respiratory, thoracic and mediastinal Disorders |
Not known |
Respiratory depression |
|
Gastrointestinal Disorders |
Not known Not known Not known Not known 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
4.9 Overdose
Signs and symptoms
Dextromethorphan is thought to be of low toxicity, but the effects in overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs.
Symptoms of overdose may include: mydriasis, nausea and vomiting, CNS depression, excitation, lethargy, nystagmus, psychomotor hyperactivity, serotonin syndrome, somnolence (drowsiness), dizziness, dysarthria (slurred speech), mental confusion, psychotic disorder (psychosis), and respiratory depression.
Management
Treatment should be symptomatic and supportive. Gastric lavage may be of use. Naloxone has been used successfully to reverse central or peripheral opioid effects of dextromethorphan in children (0.01mg/kg body weight).
5. PHARMACOLOGICAL PROPERTIES
5.1. Pharmacodynamic properties
ATC Code: R05DA09 Pharmacotherapeutic Group: Cough Suppressant, Opium alkaloids and derivatives
Dextromethorphan is the dextrorotatory isomer of 3-methoxy-N-methyl-morphinan. It is a synthetic morphine derivative that, in contrast to its levorotatory isomer, has no significant analgesic, respiratory depressant or physical dependency properties at recommended doses.
Dextromethorphan is a non-opioid antitussive drug. It exerts its antitussive activity by acting on the cough centre in the medulla oblongata, raising the threshold for the cough reflex. The onset of antitussive effects are realised within 15 to 30 minutes of oral administration, lasting for approximately 3 to 6 hours.
The major metabolite of dextromethorphan, dextrorphan, binds with high affinity to a-receptors to produce its antitussive activity without exhibiting the classic opiate effects that occur from binding into p- and 5-receptors. Dextrorphan also exhibits binding activity at serotonergic receptors and was shown to enhance serotonin activity by inhibiting the reuptake of serotonin. In larger than therapeutic doses, dextrorphan is also an antagonist of N-methyl-D-aspartate (NMDA) receptors.
5.2. Pharmacokinetic properties
Absorption
Dextromethorphan is rapidly absorbed from the gastrointestinal tract with peak plasma concentrations reached in approximately 2 to 2.5 hours. The low plasma levels of dextromethorphan suggest low oral bioavailability secondary to extensive first-pass (pre-systemic metabolism) in the liver. The maximum clinical effects occur 5 to 6 hours after ingestion of dextromethorphan.
Distribution
Dextromethorphan is widely distributed in the human body.
Dextromethorphan and its active metabolite, dextrorphan, are actively taken up and concentrated in brain tissue. It is not known if dextromethorphan or dextrorphan are excreted in breast milk or cross the placenta.
Metabolism
Dextromethorphan undergoes rapid and extensive first-pass metabolism in the liver after oral administration. As the hepatic metabolism of dextromethorphan is genetically determined, individuals vary in their ability to metabolise dextromethorphan and have been classified as either poor or extensive metabolisers. Dextromethorphan undergoes O-demethylation via CYP2D6 to dextrorphan; N-demethylation to 3-methoxymorphinan via CYP3A4/3A5; which is further metabolised to 3-hydroxy-morphinan via CYP2D6.
Excretion
Dextromethorphan is primarily excreted via the kidney as unchanged parent drug and its active metabolite, dextrorphan. Dextrorphan and 3-hydroxy-morphinan are further metabolised by glucuronidation and are eliminated via the kidneys.
The elimination half-life of the parent compound is between 1.4 to 3.9 hours; dextrorphan is between 3.4 to 5.6 hours. The half-life of dextromethorphan in poor metabolisers is extremely prolonged, in the range of 45 hours
5.3. Preclinical safety data
General toxicology
Acute oral toxicity studies conducted with Dextromethorphan report the following LD values (mg/kg): mouse, 210 and rat, 116. Acute subcutaneous
toxicity with Dextromethorphan reports the LD value (mg/kg): mouse, 112.
Acute intravenous toxicity with Dextromethorphan reports the LD value
(mg/kg): rat, 16.3.
Repeat dose toxicity studies conducted in rats for 13 weeks duration at doses up to 100 mg/kg and 27 weeks at 10 mg/kg, and of 14 weeks in dogs by oral gavage at doses up to 4 mg/kg on five days per week. The only effect recorded was of reduced body weight gain in the rat 13-week study at the highest dose.
Genetic Toxicology
Dextromethorphan hydrobromide was negative in the bacterial reverse mutation assay (Ames test). Dextromethorphan 39 mg/kg is reported to be negative in in-vivo mouse micronucleus test and comet assay. Dextromethorphan was reported to be negative in in vitro chromosome aberration assay tested up to 200 pg/ml.
Carcinogenicity
There are no known reports of animal carcinogenicity studies for Dextromethorphan. The overall weight of evidence for Dextromethorphan and its structural analogues, support the conclusion that this class of phenanthrene-based chemicals, and Dextromethorphan, in particular, are not genotoxic in vitro or in vivo
Teratogenicity
There was no association between dextromethorphan and malformations. Fertility
Mating, gestation, fertility, littering and lactation were studied in rats at doses up to 50 mg/kg and no adverse effects were found.
6. PHARMACEUTICAL PARTICULARS
6.1. List of Excipients
Liquid Glucose Sucrose
Sorbitol solution 70% (non crystallising)
Ethanol 96%
Glycerol
Saccharin sodium Citric acid monohydrate Sodium benzoate Caramel T12 Imitation peach flavour Levomenthol Carbomer Purified Water
6.2. Incompatibilities
None known
6.3. Shelf-Life
3 Years
6.4. Special Precautions for Storage
Do not store above 300C
6.5 Nature and contents of container
125 or 150 ml amber glass bottles with a 2 piece or a 3 piece plastic child resistant, tamper evident closure fitted with a polyterephtalate ethylene faced aluminium/expanded polyethylene laminated wad
6.6 Special precautions for disposal
No special requirements for disposal.
Any unused product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
McNeil Products Limited
Foundation Park
Roxborough Way
Maidenhead
Berkshire
SL6 3UG
United Kingdom
8. MARKETING AUTHORISATION NUMBER(S)
PL 15513/0051
9. DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION
16 June 1997
10 DATE OF REVISION OF THE TEXT
04/05/2016