McNeil Healthcare (Ireland) Ltd

Benylin Children's Coughs and Colds 5mg/0.625mg per 5ml Syrup

Each 5ml contains 5 mg Dextromethorphan hydrobromide and 0.625 mg Triprolidine hydrochloride.

Excipients: Each 5ml contains liquid maltitol 4080mg and methyl hydroxybenzoate (E218) 5mg.

For a full list of excipients, see section 6.1

Syrup.

Clear colourless Syrup.

Benylin Children's Coughs & Colds is indicated for the symptomatic relief of dry unproductive cough and rhinorrhoea associated with the common cold and influenza.

Adults and children 12 years and over:

Not appropriate.

Children aged 6 to 12 years:

Oral.10 ml three or four times daily

Maximum daily dose: 40 ml

Use only when simple measures have failed to provide adequate relief.

Use for more than five consecutive days is not recommended.

Children under 6 years:

Not recommended. [See Section 4.3]

Use in patients hypersensitive to the active ingredients.

Use in patients at risk of developing respiratory failure.

Use in children under 6 years of age is contraindicated.

Use with caution in renal or hepatic dysfunction.

Benylin Children's Coughs & Colds should only be used under medical supervision for persistent or chronic cough such as occurs with smoking asthma or emphysema, or where cough is accompanied by excessive secretions.

If symptoms persist, consult a doctor.

Patients who are taking other medication and/or under the care of a physician, should consult their doctor/pharmacist before taking this product.

Patients with rare hereditary problems of fructose intolerance should not take this medicine.

Not more than 4 doses should be given in any 24 hours. Do not exceed the stated dose.

Do not take with any other cough and cold medicine.

Consult a pharmacist or other healthcare professional before use in children aged 6-12 years.

This product may potentiate the effects of alcohol and other CNS depressants. The effects of anticholinergics, e.g. some psychotropic drugs and atropine, may be potentiated by this product.

Dextromethorphan HBr is primarily metabolized by the cytochrome P450 isoenzyme CYP2D6. Possible interactions may occur with inhibitors of this enzyme.

It is not known if dextromethorphan HBr or its active metabolite, dextrorphan, are excreted in breast milk or cross the placenta.

The available human data on the reproductive effects of dextromethorphan HBr do not demonstrate an increased teratogenic risk.

Results of a controlled study to determine the fetal risk in 184 women exposed to dextromethorphan HBr, 128 exposed in the first trimester of pregnancy, revealed that dextromethorphan HBr use during pregnancy did not increase the rate of major malformations compared to 184 matched controls.Fetal risk was also monitored in a large collaborative study involving 300 women who received dextromethorphan HBr during the first trimester of pregnancy. The study did not support a relationship between the drug and congenital malformations.Dextromethorphan HBr should not be used during pregnancy or lactation unless the benefit of treatment to the mother outweighs the potential risk to the fetus. (See Section 5.3, Preclinical safety data)

Benylin Children's Coughs & Colds may cause drowsiness and impair performance in tests of auditory vigilance. Children receiving this product should be carefully supervised in order to avoid accidental mishap.

Anticholinergic side effects include tachycardia, mouth dryness, gastro-intestinal disturbances e.g. colic, urinary retention and headache.

Skin rash has also been reported.

This product may act as a cerebral stimulant in children, and occasionally in adults. Central nervous system depression or excitation may occur, with symptoms such as drowsiness, dizziness, confusion, sleep disturbance, bronchoconstriction, dyspnoea and more rarely, hallucinations.

Symptoms and signs

The effects of acute toxicity from Benylin Children's Coughs & Colds may include drowsiness, lethargy, dizziness, ataxia, weakness, hypotonicity, respiratory depression, dryness of the skin and mucous membranes, tachycardia, nystagmus, hyperpyrexia, nausea and vomiting.

Although there have been no reports of convulsions with Actidil Elixir (Triprolidine Hcl 2 mg/5 ml), either in therapeutic doses or in overdose, central excitation is a feature of poisoning with antihistamines and can result in convulsions, particularly in infants.

Treatment

Necessary measures should be taken to maintain and support respiration and control convulsions. Gastric lavage should be performed if indicated.

Naloxone has been successful as a specific antagonist to dextromethorphan toxicity in a child.

Triprolidine

Triprolidine is a potent, competitive H₁ receptor antagonist. Being an alkylamine the drug possesses minimal anticholinergic activity. Triprolidine provides symptomatic relief in conditions believed to depend wholly, or partly, upon the triggered release of histamine. After the oral administration of a single dose of 2.5 mg triprolidine to adults, the onset of action, as determined by the ability to antagnose histamine-induced wheals and flares in the skin, was within 1 to 2 hours. Peak effects occurred at about 3 hours, and although activity declines thereafter, significant inhibition of histmine-induced wheals and flares still occurred 8 hours after a single dose.

Dextromethorphan

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. A single oral dose of 10-20 mg dextromethorphan produces its antitussive action within 1 hour and lasts for at least 4 hours.

Absorption

Triprolidine

Triprolidine is well absorbed from the gut following oral administration. After the administration of one ACTIFED tablet or 10 ml ACTIFED syrup ( each containing 2.5 mg triprolidine ) to healthy adult volunteers, the peak plasma concentration ( C_max ) of triprolidine was approximately 5.5 - 6.0 ng/ml, occurring at about 2.0 hours ( t_max ) for the tablet and 1.5 hours for the syrup after drug administration.

Dextromethorphan

Dextromethorphan in well absorbed from the gut following oral administration. Due to individual differences in the metabolism of dextromethorphan [See Metabolism and Elimination], pharmacokinetic values are highly variable. After the administration of a 20 mg dose of dextromethorphan to healthy volunteers, the C_max varied from < 1 mg/l to 8 mg/l, occuring within 2.5 hrs of administration.

Distribution

The apparent volume of distribution of triprolidine was approximately 6.5 l/kg for the tablet formulation and 7.5 l/kg for the syrup.

Due to extensive pre-systemic metabolism by the liver, detailed analysis of the distribution of orally administered dextromethorphan is not possible.

Metabolism and elimination

Triprolidine

The plasma half-life ( t_½) of triprolidine was approximately 3.2 hours. Animal hepatic microsomal enzyme studies have revealed the presence of several triprolidine metabolites with an oxidized product of the toluene methyl group predominating. In man, it has been reported that only about 1% of an administered dose is eliminated as unchanged triprolidine over a 24-hour period. The apparent total body clearance of triprolidine ( Cl/F ) was approximately 30 - 37 ml/min/kg. The elimination rate constant ( K_el ) was approximately 0.26 hr^-1.

Dextromethorphan

Dextromethorphan undergoes rapid and extensive first-pass metabolism in the liver after oral administration. Genetically controlled O-demethylation is the main determinant of dextromethorphan pharmacokinetics in human volunteers. It appears that there are distinct phenotypes for this oxidation process resulting in highly variable pharmacokinetics between subjects. Unmetabolised dextromethorphan, together with the three demethylated morphinan metabolites; dextrophan (also known as 3-hydroxy-N-methylmorphinan), 3- hydroxymorphinan and 3-methoxymorphinan have been identified as conjugated products in the urine. Dextrophan, which also has antitussive action, is the main metabolite.

Pharmacokinetics in Renal/Hepatic Impairment

There have been no specific studies of dextromethorphan, triprolidine or Benylin Children's Coughs & Colds in renal or hepatic impairment.

Pharmacokinetics in the Elderly

Not relevant

Mutagenicity, Carcinogenicity, Teratogenicity

There is insufficient information available to determine whether triprolidine or dextromethorphan have mutagenic, carcinogenic or teratogenic potential.

Fertility

Not relevant

Liquid Maltitol

Glycerol

Methyl hydroxybenzoate (E218)

Sodium benzoate (E211)

Saccharin sodium

Flavour (mixed fruit)

Purified water

Not applicable

3 Years

Do not store above 25°C.

Amber glass bottles with polypropylene screw caps fitted with PVDC faced wads or, a three piece plastic, child resistant, tamper evident closure fitted with a polyester faced wad or polyethylene/expanded polyethylene laminated wad. Or a two piece plastic child resistant cap fitted with a PVDC wad.

Sizes: 30 ml, 100 ml, and 125 ml

A polypropylene double ended measuring spoon is supplied with each bottle.

Not all pack sizes may be marketed

No special requirements

McNeil Healthcare (Ireland) Limited

Airton Road

Tallaght

Dublin 24

Ireland

PA 823/1/1

Date of first authorisation: 20 March 1998

Date of last renewal: 20 March 2008

April 2011