For the use only of Registered Medical Practitioners or a Hospital or a Laboratory

PIRITON CS

1. GENERIC NAME

Chlorpheniramine Maleate with Dextromethorphan Hydrobromide Syrup

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 5 ml (one teaspoonful) contains:

Chlorpheniramine Maleate IP 4 mg
Dextromethorphan Hydrobromide IP 10 mg
in a flavoured syrup base containing Menthol IP
Colour: Carmoisine

List of Excipients

Sucrose, Sodium Benzoate, Sodium Chloride, Citric Acid Monohydrate, Sodium Citrate,
Saccharin Sodium, Glycerin, Sorbitol Solution, Propylene Glycol, Colour Carmoisine,
Flavour Strawberry, Flavour Raspberry, Flavour peppermint, Menthol, Purified Water.

3. DOSAGE FORM AND STRENGTH

Syrup

For information on strength(s) refer 2. Qualitative and Quantitative Composition above.

4. CLINICAL PARTICULARS

4.1 Therapeutic Indications

PIRITON CS is indicated for the temporary relief of cough due to throat irritation, sneezing
and running nose.

4.2 Posology and Method of Administration

Oral administration only.

Do not exceed the stated dose or frequency of dosing.
The minimum interval between the doses should be 4 hours.

Adults and Children aged 12 years and over

5 ml every 4 hours

Maximum daily dose 30 ml in any 24 hours.

Children (6-12 years)

2.5 ml every 4 hours

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Maximum daily dose 15 ml in any 24 hours.

PIRITON CS should not be used in children aged less than 6 years.

Special Populations

Elderly

The elderly are more likely to experience neurological anticholinergic effects of

chlorpheniramine maleate. Consideration should be given to using a lower daily dose.

2.5 ml every 4 hours.

Maximum daily dose is 15 ml in any 24 hours.

Hepatic or Renal Impairment

Information on the use of PIRITON CS in patients with impaired liver or renal function is
limited. PIRITON CS should be used with caution in those patients, particularly in patients
with severe impairments. Patients with severe renal or liver insufficiency should have their
doses lowered or intervals between doses increased.

4.3 Contraindications

PIRITON CS is contraindicated in patients who are:

• hypersensitive to antihistamines or dextromethorphan or to any of the inactive ingredients

in the formulation (see List of Excipients, 4.8 Undesirable Effects).
• taking monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs in
the previous two weeks.
PIRITON CS is also contraindicated in the following cases:
• bronchial asthma
• chronic obstructive pulmonary disease
• pneumonia
• respiratory insufficiency
• respiratory depression
• breastfeeding

4.4 Special Warnings and Precautions for Use

PIRITON CS contains chlorphenamine, and hence should be used with caution in epilepsy;
raised intra-ocular pressure including glaucoma; prostatic hypertrophy; severe hypertension
or cardiovascular disease; hepatic impairment; renal impairment. Children and the elderly are
more likely to experience the neurological anticholinergic effects and paradoxical excitation
(e.g. increased energy, restlessness, nervousness). Avoid use in elderly patients with
confusion.

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The anticholinergic properties of chlorphenamine in PIRITON CS may cause drowsiness,
dizziness, blurred vision and psychomotor impairment in some patients which may seriously
affect ability to drive and use machinery.

Piriton CS should not be used with other antihistamine containing products, including
antihistamine containing cough and cold medicines.

Concurrent use of PIRITON CS with drugs which cause sedation such as anxiolytics and
hypnotics may cause an increase in sedative effects, therefore medical advice should be sought
before taking chlorphenamine concurrently with these medicines.

Avoid drinking alcoholic beverages while using PIRITON CS. The effects of alcohol may be
increased and therefore concurrent use should be avoided.

PIRITON CS should not be used for chronic persistent cough accompanying a disease state,
or for cough associated with excessive secretions.

In cases of productive cough with considerable mucus production (e.g., patients with
conditions
such as bronchiectasis, cystic fibrosis) or in patients with neurological illness associated with
a markedly reduced cough reflex (such as stroke, Parkinson’s disease and dementia)
antitussive
treatment should be administered with particular caution and only after careful benefit-risk
assessment (refer to 4.5 Drug Interactions).

PIRITON CS contains dextromethorphan which should not be given to patients with or at risk
of developing respiratory failure, e.g. asthma, chronic obstructive airways disease, and
pneumonia. Caution is needed in patients with a history of asthma and it should not be given
during an acute attack.

Dextromethorphan is metabolised by cytochrome P450 2D6 (CYP2D6). Serotonergic effects,

including the development of a potentially life-threatening serotonin syndrome, have been
reported for dextromethorphan with concomitant administration of serotonergic agents, such
as selective serotonin re-uptake inhibitors (SSRIs), drugs which impair metabolism of
serotonin (including monoamine oxidase inhibitors (MAOIs)) and CYP2D6 inhibitors that
may exaggerate or prolong the effects of dextromethorphan (see 4.5 Drug Interactions).

Serotonin syndrome may include mental-status changes (e.g. agitation, excitement,

confusion),
autonomic instability (e.g. diaphoresis, fever, tachycardia, tachypnea, mydriasis),
neuromuscular abnormalities (e.g. tremor, clonus, myoclonus, hyperreflexia, and pyramidal
rigidity), and/or gastrointestinal symptoms. Thus, Piriton CS should not be used with MAOIs
(see 4.3 Contraindications) and be used with caution in patients receiving other serotonergic
drugs (see 4.5 Drug Interactions)

If serotonin syndrome is suspected, treatment with should be discontinued.

The activity of this enzyme is genetically determined. About 10% of the general population
are poor CYP2D6 metabolisers. 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 (refer to 4.5 Drug Interactions).

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Due to potential histamine release PIRITON CS should be avoided in patients with the rare
disease of mastocytosis. Dextromethorphan can activate mast cells resulting in possible
histamine release with associated clinical manifestations.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose

malabsorption or sucrose-isomaltase insufficiency should not take this medicine.

PIRITON CS contains sucrose. This should be taken into account in patients with diabetes
mellitus.
Long term use increases the risk of dental caries and it is essential that adequate dental hygiene
is maintained.

Keep out of the reach and sight of children.

4.5 Drug Interactions

Chlorpheniramine Maleate

Concurrent use of chlorpheniramine and hypnotics or anxiolytics may cause an increase in

sedative effects. Concurrent use of alcohol may have a similar effect.

Chlorpheniramine inhibits phenytoin metabolism and can lead to phenytoin toxicity.

The anticholinergic effects of chlorpheniramine are intensified by MAOIs.

Dextromethorphan

Dextromethorphan possesses weak serotonergic properties. Thereby dextromethorphan may

increase the risk of serotonin toxicity (serotonin syndrome) particularly if taken with other
serotonergic agents, such as MAOIs, SSRIs and CYP2D6 inhibitors. Especially pre-treatment
or concomitant treatment with drugs that impair metabolism of serotonin, such as
antidepressants of the MAO inhibitor type, may result in the development of a serotonin
syndrome.

Dextromethorphan should not be used in patients taking monoamine oxidase inhibitors

(MAOIs) or who have taken MAOIs within the previous 14 days. The use of
dextromethorphan with, or within two weeks of taking MAOIs, may increase the risk of
serious side effects such as hypertensive crisis, hyperpyrexia and convulsions.

Dextromethorphan when used with SSRI’s (such as fluoxetine) or tricyclic antidepressants

(such as clomipramine and imipramine) may result in a “serotonin syndrome” with changes
in mental status (e.g agitation, excitement, confusion), hypertension, restlessness, myoclonus,
hyperreflexia, diaphoresis, shivering and tremor.

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

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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. The above cited effects may occur if any of
these medicines have been administered recently, even if they are no longer being taken.

Concomitant use of dextromethorphan and other CNS depressants (e.g. alcohol, narcotic
analgesics and tranquillizers) may increase the CNS depressant effects of these drugs.
If dextromethorphan is used in combination with secretolytics in patients with pre-existing
chest disease such as cystic fibrosis and bronchiectasis who are affected by mucus
hypersecretion reduced cough reflex can lead to serious accumulation of mucus.

4.6 Use in Special Populations

Fertility

Based on available non-clinical experience and observations in humans there are no reported
harmful effects of the use of dextromethorphan on reproduction or foetal development.

No data available for chlorpheniramine.

Pregnancy

The potential risk for humans is unknown. Use during the third trimester may result in
reactions in the newborn or premature neonates.

PIRITON CS should not be used during pregnancy unless considered essential by a physician.

Lactation

Chlorpheniramine maleate may inhibit lactation and may be secreted in breast milk.
The extent of excretion in breast milk is not known; therefore, the use of PIRITON CS is
contraindicated during lactation since a respiratory depressive effect on infants cannot be ruled
out.

4.7 Effects on Ability to Drive and Use Machines

PIRITON CS may cause drowsiness, dizziness, blurred vision and psychomotor impairment,
which can seriously hamper the patients' ability to drive and use machinery.

Even when used as recommended this medication may cause mild drowsiness and alter
reaction times to the extent that the ability to drive or to operate machinery is impaired. The
risk is increased when it is taken in combination with alcohol or with medications that can
impair reaction times.
Refer to 4.4 Special Warnings and Precautions For Use and 4.5 Drug Interactions.

4.8 Undesirable Effects

In absence of availability of adverse event data on the fixed dose combination of
dextromethorphan and chlorpheniramine, adverse event data of the individual ingredients is
presented below.

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The following convention has been utilised for the classification of the frequency of adverse
reactions: very common (>1/10), common (>1/100 to <1/10), uncommon (>1/1000 to <1/100),
rare (>1/10,000 to <1/1000) and very rare (<1/10,000), not known (cannot be estimated from
available data).

Chlorpheniramine Maleate

Adverse reactions identified during post-marketing use with chlorphenamine are listed below.
As these reactions are reported voluntarily from a population of uncertain size, the frequency
of some reactions is unknown but likely to be rare or very rare:

System organ class Adverse Reaction Frequency

Nervous system disorders* Sedation, somnolence Very common
Disturbance in attention, abnormal Common
coordination, dizziness, headache
Eye disorders Blurred vision Common
Gastrointestinal disorders Nausea, dry mouth Common
Vomiting, abdominal pain, diarrhoea, Unknown
dyspepsia
General disorders and Fatigue Common
administration site
conditions Chest tightness Unknown
Immune system disorders Allergic reactions, angioedema, Unknown
anaphylactic reactions
Metabolism and nutritional Anorexia Unknown
disorders
Blood and lymphatic system Haemolytic anaemia, blood Unknown
disorders dyscrasias
Musculoskeletal and Muscle twitching, muscle weakness Unknown
connective tissue disorders
Psychiatric disorders Confusion*, Common
Excitation*, irritability*, Unknown
nightmares*, depression
Renal and urinary disorders: Urinary retention Unknown
Skin and subcutaneous Exfoliative dermatitis, rash, urticaria, Unknown
disorders photosensitivity
Respiratory, thoracic and Thickening of bronchial secretions Unknown
mediastinal disorders
Vascular disorders Hypotension Unknown
Hepatobiliary disorders Hepatitis, including jaundice Unknown
Ear and labyrinth disorders Tinnitus Unknown
Cardiac disorders Palpitations, tachycardia, arrythmias Unknown
General Disorders and Fatigue Common
administration site Chest tightness Unknown
conditions
*Children and the elderly are more susceptible to neurological anticholinergic effects and paradoxical
excitation (eg increased energy, restlessness, nervousness).

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Dextromethorphan

System organ class Adverse Reaction Frequency

Psychiatric disorders Confusion Common
Drug dependence Very rare
Hallucinations Unknown
Nervous system disorders Somnolence, dizziness Very common
Vertigo, slurred speech and Unknown
nystagmus, dystonia especially in
children
Skin and subcutaneous Skin reactions such as rash with Unknown
tissue disorders pruritis
Immune system disorders Hypersensitivity, urticaria, fixed drug Unknown
eruption, anaphylactic reaction,
angioedema, bronchospasm
Gastro-intestinal disorders Gastrointestinal disorders (nausea, Common
vomiting, constipation)
General disorders and Fatigue Common
administration site
conditions

4.9 Overdose

Symptoms and Signs

The estimated lethal dose of chlorphenamine is 25 to 50mg/kg body weight. Symptoms and
signs include sedation, paradoxical excitation of the CNS, toxic psychosis, convulsions,
apnoea, anticholinergic effects, dystonic reactions and cardiovascular collapse including
arrhythmias.

In case of overdose known side effects may occur with higher frequency or severity.
Dextromethorphan overdose may be associated with nausea, vomiting, dizziness, fatigue,
dystonia, agitation, confusion, somnolence, stupor, nystagmus, cardiotoxicity (tachycardia,
abnormal ECG including QTc prolongation), ataxia, toxic psychosis with visual
hallucinations, hyperexcitability.

In the event of massive overdose, the following symptoms may be observed: coma, respiratory
depression, convulsions.
Restlessness and excitability may develop into agitation with increasing overdose. In addition,
symptoms such as psychotic disorders like disorientation and delusions up to confusional or
paranoid states, changes in blood pressure, impaired concentration and consciousness up to
coma as a sign of severe intoxication, slurred speech, changes in mood such as dysphoria and
euphoria, dysarthria, increased muscle tone, vision disturbance, convulsions, as well as
respiratory depression, and light-headedness may occur.
Dextromethorphan may increase the risk of serotonin syndrome, and this risk is increased by
overdose, particularly if taken with other serotonergic agents.
Cases of fatal outcomes have been reported with combination overdose with
dextromethorphan and other drugs (combination poisoning).

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Treatment

Management should be as clinically indicated or as recommended by the national poisons

centres where available. Symptomatic and supportive measures should be provided with
special attention to cardiac, respiratory, renal and hepatic functions and fluid and electrolyte
balance. If overdosage is by the oral route, treatment with activated charcoal should be
considered provided there are no contraindications for use and the overdose has been taken
recently (treatment is most effective if given within an hour of ingestion). Treat hypotension
and arrhythmias vigorously. CNS convulsions may be treated with i.v. diazepam.
Haemoperfusion may be used in severe cases.

The mainstay of treatment is supportive and symptomatic care. If necessary close intensive
care monitoring with symptom-related treatment should be initiated.
Activated charcoal can be administered to asymptomatic patients who have ingested
overdoses of dextromethorphan within the preceding hour.
For patients who have ingested dextromethorphan and are sedated or comatose, Naloxone, in
the usual doses for treatment of opioid overdose can be considered. Benzodiazepines for
seizures and benzodiazepines and external cooling measures for hyperthermia from serotonin
syndrome can be used.

5. PHARMACOLOGICAL PROPERTIES

5.1 Mechanism of Action/Pharmacodynamic Properties

Chlorpheniramine Maleate

Chlorphenamine is a potent antihistamine (H1-antagonist).

Antihistamines diminish or abolish the actions of histamine in the body by competitive

reversible blockade of histamine H1-receptor sites on tissues. Chlorphenamine also has
anticholinergic activity.

Antihistamines act to prevent the release of histamine, prostaglandins and leukotrienes and
have been shown to prevent the migration of inflammatory mediators. The actions of
chlorphenamine include inhibition of histamine on smooth muscle, capillary permeability and
hence reduction of oedema and wheal in hypersensitivity reactions such as allergy and
anaphylaxis.

Dextromethorphan

Dextromethorphan is a non-opioid cough suppressant. It is the methylated dextrorotatory

analogue of levorphanol, a codeine analogue. Dextromethorphan acts centrally on the cough
centre in the medulla and nucleus tractus solaris to increase the cough threshold. It does not
have classical analgesic, sedative or respiratory depressant effects at usual antitussive doses.
The onset of antitussive effect occurs within an hour and the duration of action is
approximately
3 – 6 hours.

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5.2 Pharmacokinetic Properties

Chlorpheniramine Maleate

Chlorphenamine is well absorbed from the gastro-intestinal tract, following oral

administration. The effects develop within 30 minutes, are maximal within I to 2 hours and
last 4 to 6 hours. The plasma half-life has been estimated to be 12 to 15 hours.
Chlorphenamine is metabolised to the monodesmethyl and didesmethyl derivatives. About
22% of an oral dose is excreted unchanged in the urine.

Dextromethorphan

Dextromethorphan is well absorbed from the gastrointestinal tract after oral administration.
It is metabolised in the liver, exhibiting polymorphic metabolism involving the cytochrome
P450 isoenzyme (CYP 2D6).
It is excreted in the urine as unchanged dextromethorphan and demethylated metabolites,
including dextrorphan, which has some cough suppressant activity. The plasma elimination
half-life of dextromethorphan is 1.2 to 3.9 hours. However, the rate of metabolism varies
between individuals according to phenotype (extensive v poor metabolisers), with half-life
being as long as 45 hours in patients who are poor metabolisers.

6. NONCLINICAL PROPERTIES

6.1 Animal Toxicology and Pharmacology

No information available.

7. DESCRIPTION

Syrup

Each 5 ml (one teaspoonful) contains:

Chlorpheniramine Maleate IP 4 mg
Dextromethorphan Hydrobromide IP 10 mg
in a flavoured syrup base containing Menthol IP
Colour: Carmoisine

List of Excipients

Sucrose, Sodium Benzoate, Sodium Chloride, Citric Acid Monohydrate, Sodium Citrate,
Saccharin Sodium, Glycerin, Sorbitol Solution, Propylene Glycol, Colour Carmoisine,
Flavour Strawberry, Flavour Raspberry, Flavour peppermint, Menthol, Purified Water.

8. PHARMACEUTICAL PARTICULARS

8.1 Incompatibilities

No incompatibilities have been identified

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8.2 Shelf Life

The expiry date is indicated on the label and packaging.

8.3 Packaging Information

Bottle with a measure cup.

8.4 Storage and Handling Information

Store in a well closed container at temperature not exceeding 30oC, protected from direct
sunlight.

Keep out of reach of children.

For oral use only.

It is dangerous to take this preparation except under medical supervision

9. PATIENT COUNSELLING INFORMATION

Registered Medical Practitioners may counsel their patients (and/or patients’ caregiver as
applicable) about the special warnings and precautions for use, drug interactions, undesirable
effects, and any relevant contra-indications of PIRITON CS. Patients (and/or patients’
caregiver) may also be informed about posology, method of administration and
storage/handling information as applicable.

10. DETAILS OF MANUFACTURER

The Manufacturing Site details are mentioned on the label and packaging.

For further information please contact:

GlaxoSmithKline Pharmaceuticals Limited.
Registered Office
Dr. Annie Besant Road, Worli
Mumbai 400 030, India.

11. DETAILS OF PERMISSION OR LICENCE NUMBER WITH DATE

Manufacturing License number is indicated on the label and packaging

12. DATE OF REVISION

9-Nov-2023

Trade marks are owned by or licensed to the GSK group of companies.

Version No: PIRCS/PI/IN/2023/02.

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Adapted from:

1. Piriton Syrup SmPC (last updated on emc: 17 Apr 2023). Available from:
https://www.medicines.org.uk/emc/product/3928)
2. Bisolvon Dry New Zealand Data Sheet (date of revision of text: 20 Dec 2021).
Available from:
https://www.medsafe.govt.nz/profs/datasheet/b/bisolvondryoralsolution.pdf
3. Clinical Pharmacology – Chlorpheniramine monograph. Available from:
https://www.clinicalkey.com/pharmacology/monograph/119.
4. Clinical Pharmacology - Dextromethorphan Monograph. Available from:
https://www.clinicalkey.com/pharmacology/monograph/179.

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