McNeil Healthcare (Ireland) Ltd

Benylin Cough Medicine Syrup

Diphenhydramine hydrochloride 14 mg

Levomenthol 1.1 mg

Each 5 ml contains:

Diphenhydramine hydrochloride 14 mg

Levomenthol 1.1 mg

Each 5ml also contains:

Glucose Syrup 3.49mg

Sucrose 1.0g

Ethanol 0.26ml

Ponceau 4R (E124) 0.25mg

Sodium 16.42mg

For a full list of excipients, see section 6.1

Syrup.

Clear red syrup with a taste characteristic of menthol.

(a) Properties

Fixed combination of anti-histamine with anti-tussive activity and carminative.

(b) Indications for use

In the symptomatic relief of non-productive cough and of allergic conditions and reactions.

For oral use.

Adults and children over 12 years:

One or two 5 ml spoonfuls three to four times daily.

Not recommended for children under 12 years. [see section 4.3]

Benylin Cough Medicine is contra-indicated in individuals hypersensitive to the active ingredients.

Benylin cough Medicine should not be used in children under the age of 12 years.

Patients with moderate to severe renal or hepatic dysfunction should exercise caution when using this product (see Pharmacokinetics).

This product contains diphenhydramine and therefore should not be taken by individuals with narrow-angle glaucoma or symptomatic prostatic hypertrophy unless directed by a doctor.

This product may act as a cerebral stimulant in children and occasionally in adults. Symptoms of overdosage include insomnia, nervousness, hyperpyrexia, tremors and epileptiform convulsions. Large doses of antihistamines may precipitate attacks in epilepsy.

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

Benylin Cough Medicine should not be used for persistent or chronic cough such as occurs with smoking asthma or emphysema or where cough is accompanied by excessive secretions, unless directed by a physician.

This product contains diphenhydramine and therefore may potentiate the effects of alcohol and other central nervous system depressants.

As diphenhydramine possesses some anti-cholinergic activity, the effects of anti-cholinergics (e.g. some psychotropic drugs and atropine) may be potentiated by this product giving rise to tachycardia, mouth dryness, gastrointestinal disturbances (e.g. colic), urinary retention and headache.

Although dipenhydramine has been in widespread use for many years without ill consequence, it is known to cross the placenta and has also been detected in breast milk. Benylin Cough Medicine should not be used during pregnancy unless considered essential by a doctor.

This product may cause drowsiness and patients receiving it should not drive or operate machinery unless it has been shown that their physical and mental capacity remains unaffected.

Side effects associated with the use of Benylin Cough Medicine are uncommon.

Diphenhydramine may cause drowsiness; dizziness; gastrointestinal disturbance; dry mouth, nose and throat; difficulty in urination, headache or rash.

Adverse reactions to menthol at the low concentration present are not anticipated.

Symptoms and signs

The symptoms and signs of Benylin Cough Medicine overdose may include drowsiness, hyperpyrexia, and anticholinergic effects. With higher doses, and particularly in children, symptoms of CNS excitation including insomnia, nervousness, tremors and epileptiform convulsions may appear; with massive doses, coma or cardiovascular collapse may follow.

Treatment

Treatment of overdose should be symptomatic and supportive. Measures to promote rapid gastric emptying (with syrup of ipecac-induced emesis or gastric lavage) and, in cases of acute poisoning, the use of activated charcoal, may be useful. The intravenous use of physostigmine may be efficacious in antagonising severe anticholinergic symptoms.

Diphenhydramine possesses antitussive, antihistaminic, anticholinergic properties. Experiments have shown that the antitussive effect (resulting from an action on the brainstem) is discrete from its antihistaminic effect. The duration of activity of diphenhydramine is between 4 and 8 hours.

Menthol has mild local anaesthetic and decongestant properties.

Absorption

Diphenhydramine and menthol are well absorbed from the gut following oral administration. Peak serum levels of diphenhydramine following a 50 mg oral dose are reached at between 2 and 2.5 hours.

Distribution

Diphenhydramine is widely distributed throughout the body, including the CNS. Following a 50 mg oral dose of diphenhydramine, the volume of distribution is in the range 3.3 – 6.8 L/kg, and it is some 78% bound to plasma proteins.

Metabolism and elimination

Diphenhydramine undergoes extensive first pass metabolism. Two successive N-dimethylations occur, with the resultant amine being oxidised to a carboxylic acid. Values for plasma clearance of a 50 mg oral dose of diphenhydramine 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. Menthol is hydroxylated in the liver by microsomal enzymes to p-methane-3,8 diol. This is then conjugated with glucuronide and excreted both in urine and bile as the glucuronide.

The elderly

Pharmacokinetic studies indicate no major differences in distribution or elimination of dipenhydramine compared to younger adults.

Renal dysfunction

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).

Hepatic dysfunction

After intravenous administration of 0.8 mg/kg diphenhydramine, a prolonged shelf-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.

Mutagenicity

The results of a range of tests suggest that neither diphenhydramine or menthol have mutagenic potential.

Carcinogenicity

There is insufficient information to determine the carcinogenic potential of diphenhydramine or menthol, although such effects have not been associated with these drugs in animal studies.

Teratogenicity

The results of a number of studies suggest that the administration of either diphenhydramine or menthol does not produce any statistically significant teratogenic effects in rats, rabbits and mice.

Fertility

There is insufficient information to determine whether diphenhydramine has the potential to impair fertility, although a diminished fertility rate has been observed in mice in one study.

Not applicable

3 years

Do not store above 30^°C. Keep the medicine tightly closed in the original container.

30 ml, 125 ml, 300 ml round amber glass bottle with aluminium roll on pilfer proof (ROPP) cap or a 3 piece plastic child resistant, tamper evident closure fitted with a polyester faced wad or polyethylene/expanded polyethylene laminated wad.

Not all pack sizes may be marketed.

No special requirements.

McNeil Healthcare (Ireland) Limited

Airton Road

Tallaght

Dublin 24

Ireland

PA 823/17/1

1^st April 1979 / 1^st April 2009

June 2009