- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
Adults and children aged 12 years and over:Oral. 10 ml syrup 4 times a day.
Children under 12 years:Benylin Dry Coughs (Original) is contraindicated in children under the age of 12 years (see section 4.3).
The Elderly:Normal adult dosage is appropriate, [See Pharmacokinetics in the Elderly].Do not exceed the stated dose.Keep out of the reach and sight of children.
Symptoms and signsThe effects of acute toxicity of Benylin Dry Coughs (Original) may include drowsiness, hyperpyrexia, anticholinergic effects, lethargy, nystagmus, ataxia, respiratory depression, nausea, vomiting, and hyperactivity. With higher doses, and particularly in children, symptoms of CNS excitation including hallucinations and convulsions may appear; with massive doses, coma or cardiovascular collapse may follow.
TreatmentTreatment 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. Naloxone has been used successfully as a specific antagonist to dextromethorphan toxicity in children. Convulsions may be controlled with diazepam and thiopental sodium.
DextromethorphanDextromethorphan 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.
DiphenhydramineDiphenhydramine possesses antitussive, antihistaminic, and 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.
AbsorptionDiphenhydramine, dextromethorphan 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 hrs after an oral dose. Due to individual differences in the metabolism of dextromethorphan [See Metabolism & Elimination], pharmacokinetic values are highly variable. After the administration of a 20 mg dose of dextromethorphan to healthy volunteers, the Cmax varied from < 1 µg/l to 8 µg/l, occurring within 2.5 hrs of administration.
DiphenhydramineDiphenhydramine 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.
DextromethorphanDue to extensive pre-systemic metabolism by the liver, detailed analysis of the distribution of orally administered dextromethorphan is not possible.
Metabolism and elimination
DiphenhydramineDiphenhydramine undergoes extensive first pass metabolism. Two successive N-demethylations 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.
DextromethorphanDextromethorphan 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; dextrorphan (also known as 3-hydroxy-N-methylmorphinan), 3-hydroxymorphinan and 3-methoxymorphinan have been identified as conjugated products in the urine. Dextrorphan, which also has antitussive action, is the main metabolite.
MentholMenthol 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.
Pharmacokinetics in Renal ImpairmentThe 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 the glomerular filtration rate (GFR).There have been no specific studies of Benylin Dry Coughs (Original) or dextromethorphan in renal impairment.
Pharmacokinetics in Hepatic ImpairmentAfter intravenous administration 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.There have been no specific studies of Benylin Dry Coughs (Original) or dextromethorphan in hepatic impairment.
Pharmacokinetics in the ElderlyPharmacokinetic studies indicate no major differences in distribution or elimination of diphenhydramine compared to younger adults.There have been no specific studies of Benylin Dry Coughs (Original) or dextromethorphan in the elderly.
The preparations being discontinued are:
- Benylin Dry Coughs Original oral solution (McNeil Products Ltd)
The pharmaceutical company has decided to discontinue the product and so it may not be available in the future. This document has been left on the eMC for information purposes.
McNeil Products Ltd
Foundation Park, Roxborough Way, Maidenhead, Berks, SL6 3UG