Summary of medicine characteristics - BENYLIN CHILDRENS NIGHT COUGHS
1 NAME OF THE MEDICINAL PRODUCT
BENYLIN CHILDREN’S NIGHT COUGHS
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 5ml contains:
Diphenhydramine Hydrochloride 7.0 mg
Levomenthol 0.55 mg
Each 5ml also contains:
Sorbitol (E 420) 2.53 g
Ethanol 197 mg
Sodium 16.47 mg
Sodium benzoate (E 211) 25 mg
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
A clear colourless syrup with no insoluble matter.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
BENYLIN CHILDREN’S NIGHT COUGHS is indicated for the relief of cough and its congestive symptoms, runny nose and sneezing, and in the treatment of hay fever and other allergic conditions affecting the upper respiratory tract. It is specially formulated for children and contains no artificial dyes or sucrose.
4.2 Posology and method of administration
Route of Administration: Oral
Children under 6 years:
BENYLIN CHILDREN’S NIGHT COUGHS is contraindicated in children under the age of 6 years (see section 4.3).
Children 6 to 12 years:
Two 5 ml spoonfuls every 6 hours
No more than four doses should be given in any 24 hours.
Not to be used for more than five days without the advice of a doctor. Parents or carers should seek medical attention if the child’s condition deteriorates during treatment.
Do not exceed the stated dose.
Keep out of the sight and reach of children.
4.3 Contraindications
BENYLIN CHILDREN’S NIGHT COUGHS is contraindicated in individuals with known hypersensitivity to the Diphenhydramine or Levomenthol or to any of the excipients listed in section 6.1.
BENYLIN CHILDREN’S NIGHT COUGHS should not be administered to patients currently receiving monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping treatment (see section 4.5).
Not to be used in children under the age of 6 years.
4.4 Special warnings and precautions for use
Patients with the following conditions should be advised to consult a physician before using this medicine:
A chronic or persistent cough such as occurs with emphysema or chronic bronchitis, acute or chronic asthma, or where cough is accompanied by excessive secretions
Susceptibility to angle-closure glaucoma
Prostatic hypertrophy and/or urinary retention
Diphenhydramine may enhance the sedative effects of central nervous system depressants including alcohol, sedatives, opioid analgesics, antipsychotics and tranquilizers. Alcoholic beverages should be avoided while taking this medicine (see section 4.5).
Do not use with any other product containing diphenhydramine, including topical formulations used on large areas of skin.
Patients with hepatic disease or moderate to severe renal dysfunction should exercise caution when using this product (see Pharmacokinetics -Renal/Hepatic Dysfunction).
The product may cause drowsiness. This product should not be used to sedate a child.
A dose of 10 ml of this medicine administered to a child 6 years of age and weighing 21 kg would result in exposure to 18.8 mg/kg of ethanol which may cause a rise in blood alcohol concentration (BAC) of about 3.13 mg/100 ml (see Appendix 1 of report EMA/CHMP/43486/2018).
For comparison, for an adult drinking a glass of wine or 500 ml of beer, the BAC is likely to be about 50 mg/100 ml.
Co-administration with medicines containing e.g., propylene glycol or ethanol may lead to accumulation of ethanol and induce adverse effects, in particular in young children with low or immature metabolic capacity.
This medicine contains 16.47 mg sodium (main component of cooking/table salt) in each 5 ml. This is equivalent to 0.82% of the recommended maximum daily dietary intake of sodium for an adult.
This product contains 2.53 g sorbitol in each 5 ml. The additive effect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account.
The content of sorbitol in medicinal products for oral use may affect the bioavailability of other medicinal products for oral use administered concomitantly.
Patients with hereditary problems of fructose intolerance (HFI) should not take/be given this medicinal product.
Sorbitol may cause gastrointestinal discomfort and mild laxative effect.
This medicine contains 25 mg sodium benzoate (E 211) in each 5 ml.
4.5 Interaction with other medicinal products and other forms of interaction
Diphenhydramine
CNS depressants: may enhance the sedative effects of CNS depressants including barbiturates, hypnotics, opioid analgesics, anxiolytic sedatives, antipsychotics and alcohol.
Antimuscarinic drugs: may have an additive muscarinic action with other drugs, such as atropine and some antidepressants.
MAOIs: Not to be used in patients taking MAOIs or within 14 days of stopping treatment as there is a risk of serotonin syndrome.
Menthol
There are no known drug interactions associated with menthol.
4.6 Fertility, pregnancy and lactation
This product should not be used during pregnancy or breastfeeding unless the potential benefit of treatment to the mother outweighs the possible risks to the developing fetus or breastfeeding infant.
Diphenhydramine
Pregnancy
Diphenhydramine has been in widespread use for many years without any apparent ill consequence. Diphenhydramine is known to cross the placenta and, therefore, should only be used during pregnancy if considered essential by a doctor.
Breast-feeding
Diphenhydramine is excreted into human breast milk, but levels have not been reported. Although the levels are not thought to be sufficiently high enough after therapeutic doses to affect the infant, the use of diphenhydramine during breastfeeding is not recommended.
Menthol
There are no adequate and well-controlled studies in pregnant women for menthol. Menthol is excreted in breast milk; when 100 mg of menthol was ingested, there was up to 5.87 ug/L of menthol in breast milk.
4.7 Effects on Ability to Drive and Use Machines
This preparation may cause drowsiness, dizziness or blurred vision. If affected, the patient should not drive or operate machinery.
4.8 Undesirable effects
4.8 Undesirable effectsDiphenhydramine
Adverse drug reactions (ADRs) identified during clinical trials and post-marketing experience with Diphenhydramine 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
Not known (cannot be estimated from the available data)
System Organ Class (SOC) | Frequency* | Adverse Drug Reaction |
Blood and Lymphatic System Disorders | Rare | Blood disorders |
Immune System Disorders | Rare | Hypersensitivity reactions |
Psychiatric Disorders | Uncommon | Irritability Hallucination Nervousness |
Rare | Confusional state | |
Nervous System Disorders | Very common | Somnolence (usually diminishes within a few days) |
Common | Dizziness Headache Paradoxical stimulation Psychomotor impairment | |
Uncommon | Agitation Paraesthesia Sedation | |
Rare | Convulsion Depression Extrapyramidal effects Insomnia Tremor | |
Eye Disorders | Common | Vision blurred |
Ear and Labyrinth Disorders | Uncommon | Tinnitus |
Cardiac Disorders | Uncommon | Tachycardia |
Rare | Arrhythmia Palpitations | |
Vascular Disorders | Rare | Hypotension |
Respiratory, Thoracic and Mediastinal Disorders | Common | Thickened respiratory tract secretions |
Uncommon | Chest discomfort Nasal dryness | |
Gastrointestinal Disorders | Common | Dry mouth Nausea Vomiting |
Hepatobiliary Disorders | Rare | Liver dysfunction |
Skin and Subcutaneous | Uncommon | Pruritus Rash |
System Organ Class (SOC) | Frequency* | Adverse Drug Reaction |
Tissue Disorders | Urticaria | |
Renal and Urinary Disorders | Common | Urinary retention |
General Disorders and Administration site conditions | Common | Asthenia |
(*) Frequency category based on clinical trials with single-ingredient diphenhydramine
Menthol
Adverse reactions to menthol at the low concentration present in BENYLIN CHILDREN’S NIGHT COUGHS are not anticipated.
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 or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
Signs and Symptoms
Diphenhydramine
Mild to Moderate Symptoms:
Drowsiness, anticholinergic syndrome (mydriasis, flushing, fever, dry mouth, urinary retention, decreased bowel sounds), tachycardia, mild hypertension, nausea and vomiting are common after overdose. Agitation, confusion and hallucinations may develop after moderate poisoning.
Severe Symptoms:
Effects may include delirium, psychosis, seizures, coma, hypotension, QRS widening, and ventricular dysrhythmias (including torsades de pointes), but are generally only reported in adults after large ingestions. Rhabdomyolysis and renal failure may rarely develop in patients with prolonged agitation, coma or seizure. Death may occur as a result of respiratory failure or circulatory collapse.
In children, CNS excitation, including hallucinations and convulsions may appear; with larger doses, coma or cardiovascular collapse may follow.
Menthol
Excessive use of menthol may lead to abdominal pain, vomiting, flushed face, dizziness, weakness, tachycardia, stupor, and ataxia.
Treatment
Treatment of overdose should be symptomatic and supportive. The benefit of gastric decontamination is uncertain. Consider activated charcoal (charcoal dose: 50 g for adults; 1 g/kg for children) only if the patient presents within 1 hour of ingestion of a potentially toxic amount. Seizures may be controlled with Diazepam or Thiopental Sodium. In addition to supportive care, the intravenous use of Physostigmine may be efficacious in antagonising severe anticholinergic symptoms.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Diphenhydramine is a potent antihistamine and antitussive with anticholinergic properties. Recent experiments have shown that the antitussive action is discrete from H1-receptor blockade and is located in the brain stem.
Menthol has mild local anaesthetic and decongestant properties.
5.2 Pharmacokinetic Properties
5.2 Pharmacokinetic PropertiesDiphenhydramine is well absorbed from the gastrointestinal tract. Peak serum levels are reached at between 2–2.5 hours after an oral dose. Duration of activity is between 4 – 8 hours. The drug is widely distributed throughout the body, including the CNS, and some 78% are bound to plasma proteins.
Estimates of the volume of distribution lie in the range 3.3 – 6.8 l/kg.
Diphenhydramine experiences extensive first-pass metabolism, undergoing two successive N-Demethylations; the resultant amine is then oxidised to a carboxylic acid. Values for plasma clearance lie in the range 600 – 1300 ml/min and the terminal elimination half-life lies in the range 3.4 – 9.3 hours. Little unchanged drug is excreted in the urine.
Pharmacokinetic studies in elderly subjects indicate no major differences in drug distribution or elimination compared with younger adults.
Menthol: After absorption, menthol is conjugated in the liver and excreted both in urine and bile as the glucuronide.
The results of a review on the use of diphenhydramine in renal failure suggest that in moderate to severe renal failure, the dose interval should be extended by a period dependent on Glomerular filtration rate (GFR).
After intravenous adminstration of 0.8 mg/kg diphenhydramine, a prolonged half-life was noted in patients with chronic liver disease which correlated with the severity of the disease. However, the mean plasma clearance and apparent volume of distribution were not significantly affected.
5.3 Pre-clinical Safety Data
5.3 Pre-clinical Safety DataNot applicable
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium benzoate
Citric acid monohydrate
Sodium citrate
Saccharin sodium
Sodium carboxymethylcellulose 7MXF
Glycerol
Sorbitol 70% (non crystalline)
Concentrated raspberry essence (Ethanol, Propylene Glycol
E1520)
Ethanol 96%
Purified water
6.2 Incompatibilities
None known
6.3 Shelf Life
36 months unopened
6.4 Special Precautions for Storage
Store below 30°C
6.5 Nature and contents of container
6.6 Special precautions for disposal
McNeil Products Limited 50 – 100 Holmers Farm Way High Wycombe
Buckinghamshire
HP12 4EG
UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 15513/0044