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COVONIA HOT DOSE COUGH & COLD SYRUP

Active substance(s): DEXTROMETHORPHAN HYDROBROMIDE / DIPHENHYDRAMINE HYDROCHLORIDE

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SUMMARY OF PRODUCT CHARACTERISTICS
1

NAME OF THE MEDICINAL PRODUCT
Covonia Hot Dose Cough & Cold Syrup

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Dextromethorphan Hydrobromide Ph.Eur.

6.65mg/5ml dose.

Diphenhydramine Hydrochloride Ph.Eur.

10.0mg/5ml dose.

Excipients: Each 5ml contains Liquid Maltitol 1.125g, Ethanol (Alcohol) 7.3 vol %
For a full list of excipients see section 6.1

3

PHARMACEUTICAL FORM
Oral Syrup

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
For the night time symptomatic relief of unproductive cough and congestive symptoms
associated with colds.

4.2

Posology and method of administration
Posology
Adults, the Elderly and Children over 12 years

One 15ml dose at bedtime, diluted with an equal amount of hot (not boiling) water. Sip all
the liquid within 10 minutes of being diluted. Repeat after 6 hours if required.
Children under 12 years
Do not give to children under 12 years old.

4.3

Contraindications
Contraindicated in known hypersensitivity to any of the ingredients. Contraindicated in
persons under treatment with monoamine oxidase inhibitors or within 2 weeks of
discontinuation of MAOI use.
Contraindicated in persons under treatment with selective serotonin reuptake inhibitors
(SSRIs)
Dextromethorphan, in common with other centrally acting antitussive agents, should not be
given to patients in, or at risk of developing, respiratory failure.
This medicinal product should not be used in liver dysfunction. It should not be administered
to patients where cough is associated with asthma, or patients with productive cough.
Diphenhydramine has been associated with acute attacks of porphyria and is considered
unsafe in porphyric patients.
Do not give to children under 12 years old.

4.4

Special warnings and precautions for use
Because of their antimuscarinic properties antihistamines should be used with care in
conditions such as closed angle glaucoma, urinary retention, prostatic hyperplasia or
pyeloduodenal obstruction. Caution should also be exercised in patients with epilepsy or
severe cardiovascular disorders. Caution is needed for the use of dextromethorphan in patients
with a history of asthma, or with chronic or persistent cough. This medicine should be used
with caution in atopic children due to histamine release.
Use of dextromethorphan with alcohol or other CNS depressants may increase the effects on
the CNS and cause toxicity in relatively small doses (see section 4.5).
Patients with rare hereditary problems of fructose intolerance should not take this medicine.
It also contains 7.3vol% ethanol (alcohol), i.e. up to 870mg per dose, equivalent to 22ml of
beer or 9ml of wine per dose. To be taken into account in pregnant or breast-feeding women,
children and high-risk groups such as patients with liver disease, or epilepsy.
Harmful if suffering from alcoholism.
Labels will state:

If symptoms persist consult your doctor.
Keep out of the reach and sight of children.
Do not exceed the stated dose.
Do not take with any other cough and cold medicine
Causes drowsiness which may continue the next day. If affected to not drive or operate
machinery.
Avoid alcoholic drink.

4.5

Interaction with other medicinal products and other forms of interaction
Dextromethorphan and diphenhydramine should not be used in persons under treatment with
monoamine oxidase inhibitors or within 2 weeks of discontinuation of MAOI use in view of
the potential risk of serotonin syndrome and a severe or fatal interaction (see section 4.3).
Avoid use of dextromethorphan with moclobemide or other reversible MAO-A inhibitors;
rasagiline or other MAO-B inhibitors.
Manufacturer of memantine advises avoid concomitant use with dextromethorphan.
Dextromethorphan is primarily metabolised by the cytochrome P450 isoenzyme CYP2D6;
there is the possibility of interactions with inhibitors of this enzyme, including
antiarrhythmics (amiodarone, propafenone, quinidine), antipsychotics (haloperidol,
thioridazine) and SSRIs (see section 4.3).
Dextromethorphan might exhibit additive CNS depressant effects when co-administered with
alcohol, antihistamines, psychotropics, and other CNS depressant drugs.
Cimetidine inhibits the metabolism of opioid analgesics.
Diphenhydramine as an antihistamine has additive sedative effects with alcohol and other
CNS depressants including barbiturates, hypnotics, opioid analgesics, anxiolytic sedatives and
antipsychotics. It may also have additive antimuscarinic effects with antimuscarinic drugs
such as atropine and some antidepressants.
Diphenhydramine as an antihistamine may theoretically antagonise the effect of histamine
and betahistine.
Diphenhydramine inhibits the cytochrome P450 isoenzyme CYP2D6 and may affect the
metabolism of some beta blockers and the anti depressant venlafaxine.

4.6

Pregnancy and lactation
Although dextromethorphan and diphenhydramine have been in widespread use for many
years, insufficient data are available on their use during pregnancy. Use during pregnancy is
inadvisable unless there is a clear need. Caution should, therefore, be exercised by balancing
the potential benefits of treatment against any possible hazards.
It is not known if dextromethorphan or its metabolites are excreted in human breast milk.
Diphenhydramine is excreted in breast milk but the amount has not been quantified. This
medicinal product is, therefore, best avoided during breast feeding.

4.7

Effects on ability to drive and use machines
Diphenhydramine may cause drowsiness, persons so affected should be advised not to drive
or to operate machinery.
This medicine can impair cognitive function and can affect a patient’s ability to drive safely.
This class of medicine is in the list of drugs included in regulations under 5a of the Road
Traffic Act 1988. When prescribing this medicine, patients should be told:





4.8

The medicine is likely to affect your ability to drive
Do not drive until you know how the medicine affects you
It is an offence to drive while under the influence of this medicine
However, you would not be committing an offence (called “statutory defence”) if:
° The medicine has been prescribed to treat a medical or dental problem and
° You have taken it according to the instructions given by the prescriber and in the
information provided with the medicine and
° It was not affecting your ability to drive safely

Undesirable effects
The following undesirable effects have been reported for use of dextromethorphan or sedating
antihistamines including diphenhydramine, and may arise from use of the product. The
frequency of adverse effects cannot be estimated from available data.
Undesirable effects may be attributable to both dextramethorphan and sedating antihistamines
unless otherwise stated.

Blood and the lymphatic
system disorders:

Blood disorders including agranulocytosis,
leucopenia, haemolytic anaemia, and
thrombocytopenia (attributable to sedating
antihistamines)

Psychiatric disorders:

Confusion
Excitation (attributable to dextromethorphan)

depression (attributable to sedating
antihistamines)

Nervous system disorders:

Drowsiness and lowered ability to concentrate,
dizziness, convulsions
Extrapyramidal effects, paradoxical stimulation,
headache, psychomotor impairment, tremor,
paraesthesias, sleep disturbances (attributable to
sedating antihistamines)

Eye disorders:

Blurred vision, angle-closure glaucoma
(attributable to sedating antihistamines)

Ear and labyrinth
disorders:

Tinnitus (attributable to sedating antihistamines)

Cardiac disorders:

Palpitations, arrhythmias (attributable to sedating
antihistamines)

Vascular disorders:

Hypotension (attributable to sedating
antihistamines)

Respiratory, thoracic and
mediastinal disorders:

Respiratory depression (attributable to
dextromethorphan)
Thickened respiratory tract secretions,
Bronchospasm (attributable to sedating
antihistamines)

Gastrointestinal disorders:

Gastrointestinal disturbances (including nausea,
vomiting, diarrhoea)
Dry mouth (attributable to sedating
antihistamines)

Hepatobiliary disorders:

Liver dysfunction (attributable to sedating
antihistamines)

Skin and subcutaneous
tissue disorders:

Hypersensitivity reactions including skin rash

Angioedema, sweating, hair loss (attributable to
sedating antihistamines)

Musculoskeletal, connective
tissue and bone disorders:

Myalgia (attributable to sedating antihistamines)

Renal and urinary
disorders:

Urinary retention (attributable to sedating
antihistamines)

General disorders and
administration site
conditions:

Anaphylaxis (attributable to sedating
antihistamines)

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 the Yellow
Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9

Overdose
Acute overdose of dextromethorphan does not usually result in serious signs and symptoms
unless very large amounts have been ingested. It is thought to be of low toxicity, but the
effects in overdosage will be potentiated by simultaneous ingestion of alcohol and
psychotropic drugs. Signs and symptoms of substantial overdose may include nausea and
vomiting, CNS disturbances (hyperexcitability, irritability, mental confusion, lethargy,
somnolence, ataxia, auditory and visual hallucinations, psychotic disorder), dizziness, slurred
speech, nystagmus and respiratory depression.
Mild cases of diphenhydramine overdose are mainly characterised by prominent
antimuscarinic effects including dry mouth, headache, nausea, tachycardia and urinary
retention. Larger doses produce depression or stimulation of the CNS. In small children, the
stimulatory effects predominate and clinical features include hallucinations and convulsions.
Adults usually develop drowsiness first, then convulse and lapse into coma at later stage.
Fever and flushing is seen in children but is uncommon in adults.
Gastric lavage should be used if indicated. Naloxone has been used successfully as a specific
antagonist to dextromethorphan toxicity in children (0.01mg/kg body weight). Convulsions
can be controlled with diazepam. Other treatment is supportive and symptomatic and may
include artificial respiration, external cooling for hyperpyrexia and intravenous fluids.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
ATC Code: R05DA – Opium Alkaloids and Derivatives
Dextromethorphan
Dextromethorphan is a non-opioid, centrally acting cough suppressant. It raises the threshold
for the cough reflex in the medulla oblongata. In therapeutic doses, it has no significant
analgesic, respiratory depressant, euphoriant or dependence-producing properties. It does not
inhibit ciliary function.
Diphenhydramine
Diphenhydramine is an ethanolamine H1 histamine receptor antagonist. It possesses
antitussive, sedative, antimuscarinic and antiemetic properties. Antihistamines, like
diphenhydramine, are useful for controlling nasal itching, sneezing and rhinorrhoea but are
less effective for the relief of nasal congestion.

5.2

Pharmacokinetic properties
Dextromethorphan
Dextromethorphan is rapidly absorbed from the gastrointestinal tract following oral
administration. It is subject to extensive presystematic metabolism resulting in very low peak
plasma concentrations of 1.8ng/ml within 2.5 hours of an oral dose. Peak concentrations of
the main metabolite, dextrophan occur 1-2 hours after ingestion. The terminal plasma
elimination half-life of dextrophan is about three hours.
It is not known if dextromethorphan or dextrophan is excreted into breast milk or crosses the
placenta.
Dextromethorphan is extensively metabolised in the liver. It is mainly metabolised to
dextrophan by O-demethylation involving the cytochrome P45011D6 isozyme, which is then
conjugated by UDP-glucuronosyl transferases. Up to 9% of individuals have been found to
be poor metabolisers and the half-life of dextromethorphan may be extremely prolonged in
these people.

Less than 1% of the dose of dextromethorphan is excreted in the faeces. Urinary excretion of
parent drug and metabolites accounts for up to 50% of the ingested dose over 24 hours.
Diphenhydramine
Diphenhydramine is well absorbed from the gastrointestinal tract but its availability varies
between 26 and 60% due to first pass metabolism. Peak plasma concentrations are achieved
about 1 to 4 hours after oral administration. The plasma elimination half-life is 3.3 hours.
Diphenhydramine is widely distributed throughout the body including the CNS. It crosses the
placenta and has been detected in breast milk. It is highly (85-98%) bound to plasma
proteins.
Orientals have lower plasma levels, lower protein binding and a higher volume of distribution
and higher plasma clearance, but not half-life, than Caucasians.
Diphenhydramine is extensively metabolised mainly in the liver. It is N-demethylated to
monodesmethyldiphenhydramine and didesmethyldiphenhydramine. The resultant primary
amine is oxidatively deaminated to yield the carboxylic acid, diphenylmethoxy acetic acid
which may be conjugated with glutamine or glycine.
Diphenhydramine is excreted mainly in the urine with very little excreted as unchanged drug.

5.3

Preclinical safety data
Dextromethorphan
A 13 weeks dietary study in rats has shown no evidence of toxicity at the 0.1mg/kg
dextromethorphan level. Dextromethorphan has been reported to have no mutagenic potential
in two species and no effect on perinatal or postnatal mortality in high doses.
Diphenhydramine
In the rat, administration of 12mg/kg i.p. diphenhydramine hydrochloride has been reported to
produce foetal mortality and mortality in the offspring up to the tenth day after birth. Doses
up to 20 and 25 times the human dose (on a mg/kg basis) exert no teratogenic effects in rats
and rabbits.
There is no evidence for diphenhydramine being mutagenic or carcinogenic in man.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Sodium Benzoate
Ethanol (96%)
Hydroxyethylcellulose. (Natrosol G PH).
Povidone K30.
Glycerol.
Liquid Sorbitol Non-Crystallising.
Liquid Maltitol
Saccharin Sodium.
Capsicum Tincture.
Menthol.
Peppermint Oil.
Anise Oil.
Citric Acid Monohydrate.
Macrogol Cetostearyl Ether
Caramel.
Blackcurrant Flavour 1122267 – containing propylene glycol.
Purified Water.

6.2

Incompatibilities
None.

6.3

Shelf life
36 months.

6.4

Special precautions for storage
Store below 25oC. Protect from light.

6.5

Nature and contents of container
150ml amber soda glass bottle with 28mm tamper evident child resistant closure with EPE/
Saranex liner.
30ml CE marked polypropylene dosing cup with a 15 ml graduation.

6.6

Special precautions for disposal
Any unused product or waste material should be disposed of in accordance with local
requirements.

7

MARKETING AUTHORISATION HOLDER
Thornton & Ross Ltd.
Linthwaite Laboratories
Huddersfield
HD7 5QH.

8

MARKETING AUTHORISATION NUMBER(S)
PL: 00240/0364

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
26/08/2010

10

DATE OF REVISION OF THE TEXT
30/07/2015

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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