Benylin Dual Action Dry Syrup

Text that has been highlighted and underlined has been added, text that has been struck through has been removed:

4.4 Special warnings and precautions

for use

Benylin Dual Action Dry Syrup may cause

drowsiness. This product should not be used

to sedate a child

If any of the following occur, this product

should be stopped:



Hallucinations

 



Restlessness

 



Sleep disturbances

 

Patients with the following conditions should

be advised to consult a physician before

using this product:



Susceptibility to angle-closure

 



Urinary retention or prostatic

 

enlargement,



A respiratory condition such as

 

emphysema, chronic bronchitis, or

acute or chronic bronchial asthma.

Although pseudoephedrine has virtually no

pressor effects in normotensive patients,

Benylin Dual Action Dry Syrup should be

used with caution in patients taking tricyclic

antidepressants, or other sympathomimetic

agents (such as appetite suppressants and

amphetamine-like psychostimulants). The

physician or pharmacist should check that

sympathomimetic containing preparations are

not simultaneously administered by several

routes i.e. orally and topically (nasal, aural

and eye preparations).

Pseudoephedrine may act as a cerebral

stimulant giving rise to insomnia,

nervousness, hyperpyrexia, tremor and

epileptiform convulsions.

Triprolidine may enhance the sedative effects

of central nervous system depressants

including alcohol, sedatives and tranquilisers.

Use of dextromethorphan with alcohol or

other CNS depressants may increase the

effects on the CNS and cause toxicity in

relatively smaller doses.

Cases of dextromethorphan abuse have

been reported. Caution is particularly

recommended for adolescents and young

adults as well as in patients with a history

of drug abuse or psychoactive substances.

Dextromethorphan is metabolised by

hepatic cytochrome P450 2D6. The activity

of this enzyme is genetically determined.

About 10% of the general population are

poor metabolisers of CYP2D6. Poor

metabolisers and patients with

concomitant use of CYP2D6 inhibitors

may experience exaggerated and/or

prolonged effects of dextromethorphan.

Caution should therefore be exercised in

patients who are slow metabolizers of

CYP2D6 or use CYP2D6 inhibitors (see

also section 4.5).

While taking this product, patients should be

advised to avoid alcoholic drinks and consult

a healthcare professional prior to taking with

central nervous system depressants.

Benylin Dual Action Dry Syrup 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 or get worse, stop use

and 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.

Use with caution in moderate to severe renal

impairment or in hepatic impairment.

Use with caution in occlusive vascular disease.

This product should be used with caution in

atopic children due to histamine release.

This medicine contains 5% v/v ethanol

(alcohol), which is up to 190 mg per ml, equal

to 5ml beer or 2ml wine per 5 ml. This can be

harmful for those suffering from alcoholism.

The ethanol content should be taken into

account in pregnant or breastfeeding women,

children and high-risk groups such as patients

with liver disease and epilepsy.

Methyl hydroxybenzoate (E218) may cause

allergic reactions such as skin rash; this may

happen after a few days.

The colouring in this medicine may cause

allergic reactions.

Each 5ml of this medicine contains 2.8 g of

sucrose per dose. This should be taken into

account in patients with diabetes mellitus.

Patients with rare hereditary problems of

fructose intolerance, glucose-galactose

malabsorption or sucrase-isomaltase

insufficiency 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.

4.5 Interaction with other medicaments

and other forms of interaction

Triprolidine may enhance the sedative

effects of alcohol and other central nervous

system depressants including barbiturates,

hypnotics, opioid analgesics, anxiolytic

sedatives and antipsychotics.

Concomitant use with sympathomimetic

agents such as decongestants, tricyclic

antidepressants, appetite suppressants and

amfetamine-like psychostimulants, may

cause a rise in blood pressure.

Pseudoephedrine exerts its vasoconstricting

properties by stimulating adrenergic

receptors and displacing noradrenaline from

neuronal storage sites. Since MAOIs impede

the metabolism of sympathomimetic amines

and increase the store of releasable

noradrenaline in adrenergic nerve endings,

MAOIs may potentiate the pressor effect of

pseudoephedrine.

MAOIs and/or RIMAs: Benylin Dual Action

Dry Syrup should not to be given to patients

treated with MAOIs or within 14 days of

stopping treatment as there is a risk of

hypertensive crisis and serotonin syndrome

(pyrexia, hypertension, arrhythmias).

Moclobemide: risk of hypertensive crisis.

Because of its pseudoephedrine content, the

product may partially reverse the hypotensive

action of antihypertensive drugs which

interfere with sympathetic activity including

bretylium, betanidine, guanethidine,

debrisoquine, methyldopa, adrenergic

neurone blockers and beta-blockers.

Furazolidone causes a dose-related inhibition

of monoamine oxidase. Although there are

no reports to date of hypertensive crisis

caused by concurrent use with this product,

the combination should be avoided.

Oxytocin: risk of hypertension.

Cardiac glycosides: increased risk of

dysrhythmias.

Ergot alkaloids (ergotamine &

methysergide): increased risk of ergotism.

Anticholinergic drugs: enhances effects of

anticholinergic drugs (such as tricyclic

antidepressants and atropine).

Concurrent use with halogenated anaesthetic

agents such as chloroform, cyclopropane,

halothane, enflurane or isoflurane may

provoke or worsen ventricular arrhythmias.

CYP2D6 inhibitors

Dextromethorphan is metabolized by

CYP2D6 and has an extensive first-pass

metabolism. Concomitant use of potent

CYP2D6 enzyme inhibitors can increase

the dextromethorphan concentrations in

the body to levels multifold higher than

normal. This increases the patient's risk

for toxic effects of dextromethorphan

(agitation, confusion, tremor, insomnia,

diarrhoea and respiratory depression) and

development of serotonin syndrome.

Potent CYP2D6 enzyme inhibitors include

fluoxetine, paroxetine, quinidine and

terbinafine. In concomitant use with

quinidine, plasma concentrations of

dextromethorphan have increased up to

20-fold, which has increased the CNS

adverse effects of the agent. Amiodarone,

flecainide and propafenone, sertraline,

bupropion, methadone, cinacalcet,

haloperidol, perphenazine and

thioridazine also have similar effects on

the metabolism of dextromethorphan. If

concomitant use of CYP2D6 inhibitors and

dextromethorphan is necessary, the

patient should be monitored and the

dextromethorphan dose may need to be

reduced.

 

Dextromethorphan is primarily

 

metabolized by the cytochrome P450

isoenzyme CYP2D6, an interaction with

quinidine (CYP2D6 inhibitor) leading to

increased dextromethorphan plasm

concentrations have been described

5.2. Pharmacokinetic properties

After the administration of 2.5 mg

triprolidine hydrochloride and 60 mg

pseudoephedrine hydrochloride to healthy

adult volunteers, the peak plasma

concentration (Cmax) of triprolidine is

approximately 5.5 ng/ml - 6.0 ng/ml

occurring at about 1.5 - 2.0 hours (Tmax)

after drug administration. Its plasma half-life

is approximately 3.2 hours. The Cmax of

pseudoephedrine is approximately 180 ng/ml

with Tmax approximately 1.5 - 2.0 hours

after drug administration. The plasma halflife

is approximately 5.5 hours (urine pH

maintained between 5.0 - 7.0). The plasma

half-life of pseudoephedrine is increased in

subjects with alkaline urine and decreased in

subjects with acid urine.

Genetically controlled O-demethylation is

the main determinant of dextromethorphan

pharmacokinetics in human volunteers. It

appears that there are two distinct

phenotypes for this oxidation process

resulting in highly variable pharmacokinetics

between subjects.

Dextromethorphan undergoes rapid and

extensive first-pass metabolism in the

liver after oral administration.

Genetically controlled O-demethylation

(CYD2D6) 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-Nmethylmorphinan),

3- hydroxymorphinan

and 3-methoxymorphinan have been

identified as conjugated products in the

urine.

Dextrorphan, which also has antitussive

action, is the main metabolite. In some

individuals metabolism proceeds more

slowly and unchanged dextromethorphan

predominates in the blood and urine.

 

10           Date of revision

 23 December 2016

Section 4.2 Removed text "for oral use" and "Not recommended"

Added text "Posology" "Maximum daily dose: 40ml (80mg dextromethorphan, 240mg pseudoephedrine and 10mg triprolidine)." "The medicine is contraindicated in children under the age of 12 years."
"Use in the elderly
There have been no specific studies of Benylin Dual Action Dry Syrup in the elderly. Experience has indicated that normal adult dosage is appropriate.
Hepatic Dysfunction
Caution should be exercised when administering Benylin Dual Action Dry Syrup to patients with severe hepatic impairment.
Renal Dysfunction
Caution should be exercised when administering Benylin Dual Action Dry Syrup to patients with moderate to severe renal impairment
Method of administration
For oral use.
Do not exceed the stated dose."

Section 4.3 Removed text "hypersensitive to the product or any of its ingredients." "severe" "or severe coronary artery disease and" "Benylin Dual Action Dry Syrup is contraindicated in patients where cough is associated with asthma or where cough is accompanied by excessive secretions."

Added text "individuals with hypersensitivity to dextromethorphan, pseudoephedrine, triprolidine or to any of the excipients listed in section 6.1." "There is a risk of serotonin syndrome with dextromethorphan and the concomitant use of pseudoephedrine and MAOIs may cause a rise in blood pressure or hypertensive crisis (see section 4.5)
Benylin Dual Action Dry Syrup is contraindicated in individuals who are concomitantly taking other sympathomimetic decongestants.
Benylin Dual Action Dry Syrup is contraindicated in individuals who have diabetes mellitus, phaeochromocytoma, hyperthyroidism, closed angle glaucoma or severe renal impairment." "cardiovascular disease" "and in those who are taking beta-blockers (see section 4.5).This product is contraindicated in patients taking selective serotonin reuptake inhibitors. (SSRIs, see section 4.5)." "in, or"

Section 4.4 Removed text "As with other sympathomimetic agents, Benylin Dual Action Dry Syrup should be used with caution in patients with hypertension, heart disease, diabetes, hyperthyroidism, elevated intraocular pressure and prostatic enlargement." "please"

Added text "Benylin Dual Action Dry Syrup may cause drowsiness. This product should not be used to sedate a child"
"If any of the following occur, this product should be stopped:
• Hallucinations
• Restlessness
• Sleep disturbances
Patients with the following conditions should be advised to consult a physician before using this product:
• Susceptibility to angle-closure
• Urinary retention or prostatic enlargement,
• A respiratory condition such as emphysema, chronic bronchitis, or acute or chronic bronchial asthma.
Although pseudoephedrine has virtually no pressor effects in normotensive patients, Benylin Dual Action Dry Syrup should be used with caution in patients taking tricyclic antidepressants, or other sympathomimetic agents (such as appetite suppressants and amphetamine-like psychostimulants). The physician or pharmacist should check that sympathomimetic containing preparations are not simultaneously administered by several routes i.e. orally and topically (nasal, aural and eye preparations).
Pseudoephedrine may act as a cerebral stimulant giving rise to insomnia, nervousness, hyperpyrexia, tremor and epileptiform convulsions.
Triprolidine may enhance the sedative effects of central nervous system depressants including alcohol, sedatives and tranquilisers.
Use of dextromethorphan with alcohol or other CNS depressants may increase the effects on the CNS and cause toxicity in relatively smaller doses.
While taking this product, patients should be advised to avoid alcoholic drinks and consult a healthcare professional prior to taking with central nervous system depressants." "Syrup" "or get worse, stop use and" "moderate to" "impairment" "in"
"Use with caution in occlusive vascular disease.
This product should be used with caution in atopic children due to histamine release.
This medicine contains 5% v/v ethanol (alcohol), which is up to 190 mg per ml, equal to 5ml beer or 2ml wine per 5 ml. This can be harmful for those suffering from alcoholism. The ethanol content should be taken into account in pregnant or breastfeeding women, children and high-risk groups such as patients with liver disease and epilepsy.
Methyl hydroxybenzoate (E218) may cause allergic reactions such as skin rash; this may happen after a few days.
The colouring in this medicine may cause allergic reactions.
Each 5ml of this medicine contains 2.8 g of sucrose per dose. This should be taken into account in patients with diabetes mellitus."

Section 4.5 Removed text "This product" "potentiate" "or with monoamine oxidase inhibitors which interfere with the catabolism of sympathomimetic amines," "alpha" "adrenergic blocking agents"

Added text "Triprolidine" "enhance" "sedative" "including barbiturates, hypnotics, opioid analgesics, anxiolytic sedatives and antipsychotics"
"Pseudoephedrine exerts its vasoconstricting properties by stimulating adrenergic receptors and displacing noradrenaline from neuronal storage sites. Since MAOIs impede the metabolism of sympathomimetic amines and increase the store of releasable noradrenaline in adrenergic nerve endings, MAOIs may potentiate the pressor effect of pseudoephedrine.
MAOIs and/or RIMAs: Benylin Dual Action Dry Syrup should not to be given to patients treated with MAOIs or within 14 days of stopping treatment as there is a risk of hypertensive crisis and serotonin syndrome (pyrexia, hypertension, arrhythmias).
Moclobemide: risk of hypertensive crisis." "antihypertensive" "adrenergic neurone blockers" "blockers"
"Oxytocin: risk of hypertension.
Cardiac glycosides: increased risk of dysrhythmias.
Ergot alkaloids (ergotamine & methysergide): increased risk of ergotism.
Anticholinergic drugs: enhances effects of anticholinergic drugs (such as tricyclic antidepressants and atropine).
Concurrent use with halogenated anaesthetic agents such as chloroform, cyclopropane, halothane, enflurane or isoflurane may provoke or worsen ventricular arrhythmias.
Dextromethorphan is primarily metabolized by the cytochrome P450 isoenzyme CYP2D6, an interaction with quinidine (CYP2D6 inhibitor) leading to increased dextromethorphan plasm concentrations have been described."

Section 4.6 Replaced "P" with "p" in "pregnancy"

Added text "Fertility" "This product should not be used during pregnancy or lactation unless the potential benefit of treatment to the mother outweights the possible risks to the developing foetus or nursing infant.
Fertility
There is no experience of the effect of Benylin Dual Action Dry Syrup on human fertility.
Pregnancy
There are no adequate and well controlled studies available on the effects of administration of this product in pregnant women.
Breastfeeding
Pseudoephedrine distributes into and is concentrated in breast milk. In a limited study, three mothers nursing healthy infants were given an antihistamine-decongestant preparation containing 60mg of pseudoephedrine and 2.5 mg of triprolidine. Milk concentrations of pseudoephedrine were higher than plasma levels in all three patients, with peak milk concentrations occurring at 1.0-1.5 hours. The investigators calculated that 1000ml of milk produced during 24 hours would contain approximately 0.5%-0.7% of the maternal dose. However, following a single-blind, crossover study of a single dose of pseudoephedrine 60mg vs. placebo conducted in 8 lactating mothers, and assuming maternal intake of 60mg pseudoephedrine hydrochloride four times daily, the estimated infant dose of pseudoephedrine based on AUC and an estimated milk production rate of 150 ml/kg/day was 4.3% (95% CI, 3.2, 5.4%; range 2.2 to 6.7%) of the weight-adjusted maternal dose.
Triprolidine is excreted in breast milk, it has been estimated that approximately 0.06 to 0.2% of a single 2.5 mg dose of triprolidine ingested by a nursing mother will be excreted in the breast-milk over 24 hours.

Removed text "Although pseudoephedrine, dextromethorphan and triprolidine have been in widespread use for many years without apparent ill consequence, there are no specific data on their use during pregnancy. Caution should therefore be exercised by balancing the potential benefit of treatment to the mother against any possible hazards to the developing foetus. The product should not be used in pregnancy unless considered essential by the physician."
"Pseudoephedrine and triprolidine are excreted in breast milk in small amounts, but the effect of this on breast-fed infants is not known.
There is no experience of the effect of Benylin Dual Action Dry Syrup on human fertility."

Section 4.8 Removed text "The 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, sleep disturbance and more rarely, hallucinations.
This product may potentiate the effects of alcohol and other central nervous system depressants.
Anti-cholinergic side effects include tachycardia, dryness of mouth, nose and throat, gastrointestinal disturbances, e.g. colic, urinary retention and headache. Skin rash has also been reported.
The product can occasionally cause drowsiness, dizziness, confusion, excitation, gastrointestinal disorders, bronchoconstriction and dyspnoea"

"Occasionally" "Occasionally" "disturbance" and "excitation" in Psychiatric Disorders

"Occasionally" "Occasionally" and "Drowsiness" in Nervous System Disorders

"Occasionally" "ness of" (as in "Dryness of Throat") and "of nose" (as in "dryness of nose") in Respiratory Thoracic and Mediastinal Disorders

"Occasionally" "ness of" (as before) and "Colic" from Gastrointestinal Disorders

"Skin" from Skin and Subcutaneous Tissue Disorders

Added text "Placebo controlled studies with sufficient adverse event data were not available for the combination of dextromethorphan, pseudoephedrine and triprolidine.
Adverse drug reactions identified during clinical trials and post-marketing experience with dextromethorphan, pseudoephedrine or the combination of pseudoephedrine and triprolidine or the combination of dextromethorphan and pseudoephedrine are listed below by System Organ Class (SOC). The frequencies are defined in accordance with current guidance, as:
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)
ADRs are presented by frequency category based on 1) incidence in adequately designed clinical trials or epidemiology studies, if available, or 2) when incidence cannot be estimated, frequency is listed as ‘Not known’.

System Organ Class (SOC) Frequency Adverse Drug Reaction (Preferred Term) Blood and Lymphatic System Disorders Rare Blood disorder Immune System Disorders Not known Rare Drug hypersensitivity Hypersensitivity – cross-sensitivity may occur with other sympathomimetics Psychiatric Disorders Common Common Rare Rare Rare Not known Not known Not known Not known Not known Not known Not known Insomnia Nervousness [Confusion]al state Depression Sleep disturbance disorder Agitation Anxiety Delusion Euphoric mood [Hallucination]s Irritability Restlessness Nervous System Disorders Very Common Common Common Common Common Rare Rare Rare Not known Headache   Paradoxical drug reaction Psychomotor hyperactivity Somnolence Convulsion Extrapyramidal disorder Tremor Paraesthesia Eye Disorders Common Vision blurred Cardiac Disorders Rare Rare Not known Arrhythmia Palpitations   Vascular Disorders Rare Not known Hypotension Hypertension Respiratory, Thoracic and Mediastinal Disorders Common Not known Not known Not known Not known Not known Increased viscosity of bronchial secretion [Dry] Throat   Epistaxis Nasal Dryness Respiratory Depression Gastrointestinal Disorders Common Common Common Not Known Not Known Not Known   [Gastrointestinal disorder]s Nausea Abdominal pain Diarrhoea Vomiting Hepatobiliary Disorders Rare Liver disorder Skin and Subcutaneous Tissue Disorders Not Known Not Known Not Known Not Known Angioedema Pruritus R[ash] Urticaria Renal and Urinary Disorders Common Not Known [Urinary retention]* Dysuria General Disorders and Administration Site Conditions Not Known Not Known Fatigue Feeling Jittery

 
*in male patients in whom prostatic enlargement could have been an important predisposing factor.

Section 4.9 Added text "Dextromethorphan
It is thought to be of low toxicity, but the effects in overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs.
Symptoms: These include nausea, vomiting, dizziness and, dysarthria (slurred speech).,
Overdose may also result in mydriasis, CNS depression, CNS excitation, nystagmus, somnolence (drowsiness) , mental confusion, psychotic disorder (psychosis), serotonin syndrome and respiratory depression
Pseudoephedrine
Overdosage may result in:
Metabolism and nutrition disorders: hyperglycaemia, hypokalaemia.
Psychiatric disorders: CNS stimulation, insomnia; irritability, restlessness, anxiety, agitation; confusion, delirium, hallucinations, psychoses.
Nervous system disorders: convulsions, tremor, intracranial haemorrhage including intracerebral haemorrhage, drowsiness in children.
Eye disorders: mydriasis.
Cardiac disorders: palpitations, tachycardia, reflex bradycardia, supraventricular and ventricular arrhythmias, dysrhythmias, myocardial infarction.
Vascular disorders: hypertension, hypertensive crisis.
Gastrointestinal disorders: nausea, vomiting, ischaemic bowel infarction.
Musculoskeletal and connective tissue disorders: rhabdomyolysis.
Renal and urinary disorders: acute renal failure, difficulty in micturition
:
Triprolidine
Overdosage of an H1 receptor antagonist may result in CNS depression, hyperthermia, anticholinergic syndrome (mydriasis, flushing, fever, dry mouth, urinary retention, decreased bowel sounds), tachycardia, hypotension, hypertension, nausea, vomiting, agitation, confusion, hallucinations, psychosis, seizures, or dysrhythmias. Rhabdomyolysis and renal failure may rarely develop in patients with prolonged agitation, coma, or seizures. Management"
"of overdose should be symptomatic and supportive" "to reverse central or peripheral opioid effects of dextromethorphan in children (0.01 mg/kg body weight)"

Removed text "as a specific antagonist to dextromethorphan toxicity in a child."

Added to 4.8:

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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail:medsafety@hpra.ie.



Section 4.2:

Indication for use in children under 12 removed.

Section 4.3:

Contraindication not to use in children under 12 added.

Section 10:

Changed to June 2009

Change from "Plastic" to "HDPE"

To change the MAH from Pfizer Consumer Healthcare, Pottery Road, Dun Laoghaire, Co. Dublin to McNeil Healthcare (Ireland) Limited, Airton Road, Tallaght, Dublin 24, Ireland.

Correct Marketing authorisation number added