Benylin Dry Coughs Syrup

Do not use with any other product containing

diphenhydramine, even one used on skin

This product may cause drowsiness, (See

section 4.8 Undesirable Effects) if affected;

individuals should not drive or operate

machinery.

Caution should be exercised if moderate to

severe renal and/or hepatic impairment is

present, [See Pharmacokinetics].

This product may act as a cerebral stimulant

in children and occasionally in adults.

Patients with the following conditions should

be advised to consult a physician before

using this product:

• Persistent or chronic cough such as occurs

with smoking, asthma or emphysema or

where cough is accompanied by excessive

secretions

• Narrow angle glaucoma.

• Prostate hyperplasia with urinary retention.

If symptoms persist, please consult your

doctor.

Patients who are taking other medication and

/ or under the care of a physician, should

consult their doctor / pharmacist before

taking this product.

Diphenhydramine may enhance the sedative

effects of central nervous system depressants

including alcohol, sedatives, and

tranquilizers. Patients should be advised

while taking this product, to avoid alcoholic

beverages and consult a healthcare

professional prior to taking with central

nervous system depressants (see Section 4.5).

This product contains Ponceau 4R (E124) red

colouring which may cause allergic reactions.

This product contains 16.7mg sodium per

5ml. This should be taken into consideration

by those on a controlled sodium diet.

Patients with rare hereditary problems of

fructose intolerance, glucose-galactose

malabsorption or sucrase-isomaltase

insufficiency should not take this medicine.

This medicinal product contains 5 vol %

ethanol (alcohol), i.e. up to 200 mg per 5ml

dose, equivalent to approximately 5 ml beer,

2 ml wine per 5 ml dose. 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.

Do not exceed the recommended dose

schedule

This product contains diphenhydramine and

therefore may potentiate the effects of

alcohol and other CNS depressants such as

opioid analgesics, anticonvulsants,

antidepressants, antihistamines, antiemetics,

antipsychotics, anxiolytics and hypnotics.

None known.

Diphenhydramine, 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 C

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.

Due to extensive pre-systemic metabolism by

the liver, detailed analysis of the distribution of

orally administered dextromethorphan is not

possible.

Diphenhydramine undergoes extensive first

pass metabolism. Two successive Ndemethylations

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.

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; 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.

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 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 or dextromethorphan

in renal impairment.

After intravenous administration of 0.8

mg/kg diphenhydramine, a prolonged halflife

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 or dextromethorphan

in hepatic impairment.

Pharmacokinetic 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 or dextromethorphan

in the elderly.