PARACETAMOL AND CODEINE CAPLETS

Active substance: PARACETAMOL POWDER

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Paracetamol and Codeine Caplets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Active ingredient
Paracetamol pdr Ph Eur
Codeine phosphate Ph Eur

3

mg/tablet
500.0
8.00

PHARMACEUTICAL FORM
Tablet

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
This medicine is indicated in patients older than 12 years of age.
For the short term treatment of acute moderate pain which is not considered to be
relieved by other analgesics (e.g. paracetamol, ibuprofen or aspirin) alone, such as:
headache, period pains, neuralgia, toothache and rheumatic pains.
For oral administration.

4.2

Posology and method of administration
Adults over 18 years: 1 to 2 tablets
This dose may be taken with water every four to six hours if required, up to a
maximum of 8 tablets in 24 hours.
Children aged 12 years to 18 years:
The recommended dose for children 12 years and older is 1 to 2 tablets every 6 hours
when necessary up to a maximum of 8 tablets in 24 hours.
Children aged less than 12 years:
Codeine should not be used in children below the age of 12 years because of the risk
of opioid toxicity due to the variable and unpredictable metabolism of codeine to
morphine (see sections 4.3 and 4.4).
Elderly: The normal dose is considered appropriate in elderly patients.

Do not take for more than 3 days continuously without medical review.

4.3

Contraindications
Hypersensitivity to any of the ingredients. Severe liver disease.
In all paediatric patients (0-18 years of age) who undergo tonsillectomy and/or
adenoidectomy for obstructive sleep apnoea syndrome due to an increased risk of
developing serious and life threatening adverse reactions (see section 4.4).
In women during breastfeeding (see section 4.6).
In patients for whom it is known they are CYP2D6 ultra-rapid metabolisers.

4.4

Special warnings and precautions for use
Should be taken with caution by patients with impaired kidney or liver function. The
hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease.
Do not take more medicine than the label tells you to.
If you do not get better, talk to your doctor.
Keep all medicines out of the reach of children.
Do not take anything else containing paracetamol while taking this medicine.
The label will state:
Talk to a doctor at once if you take too much of this medicine, even if you feel well.
Front of pack
• Can cause addiction
• For three days use only
Back of pack
• List of indications as agreed in 4.1 of the SPC
• If you need to take this medicine continuously for more than 3 days you should
see your doctor or pharmacist
• This medicine contains codeine which can cause addiction if you take it
continuously for more than 3 days. If you take this medicine for headaches for
more than 3 days it can make them worse
The leaflet (or combined label/leaflet) will state:
Talk to a doctor at once if you take too much of this medicine, even if you feel well.
This is because too much paracetamol can cause delayed, serious liver damage.
‘Headlines’ section (to be prominently displayed)
• This medicine can only be used for.....(indications)
• You should only take this product for a maximum of 3 days at a time. If you
need to take it for longer than 3 days you should see your doctor or pharmacist
for advice
• This medicine contains codeine which can cause addiction if you take it



continuously for more than 3 days. This can give you withdrawal symptoms
from the medicine when you stop taking it
If you take this medicine for headaches for more than 3 days it can make them
worse

‘What this medicine is for’ section
• Succinct description of the indications from 4.1 of the SPC
‘Before you take this medicine’ section
• This medicine contains codeine which can cause addiction if you take it
continuously for more than 3 days. This can give you withdrawal symptoms
from the medicine when you stop taking it
• If you take a painkiller for headaches for more than 3 days it can make them
worse
‘How to take this medicine’ section
• Do not take for more than 3 days. If you need to use this medicine for more than
3 days you must speak to your doctor or pharmacist
• This medicine contains codeine and can cause addiction if you take it
continuously for more than 3 days. When you stop taking it you may get
withdrawal symptoms. You should talk to your doctor or pharmacist if you think
you are suffering from withdrawal symptoms
‘Possible side effects’ section
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any
possible side effects not listed in this leaflet. You can also report side effects directly
via the Yellow Card Scheme at: www.mhra.go.uk/yellowcard. By reporting side
effects you can help provide more information on the safety of this medicine.
‘How do I know if I am addicted?’ section
If you take the medicine according to the instructions on the pack it is unlikely that
you will become addicted to the medicine. However, if the following apply to you it
is important that you talk to you doctor:
• You need to take the medicine for longer periods of time
• You need to take more than the recommended amount
• When you stop taking the medicine you feel very unwell but you feel better if you
start taking the medicine again
CYP2D6 metabolism
Codeine is metabolised by the liver enzyme CYP2D6 into morphine, its active
metabolite. If a patient has a deficiency or is completely lacking this enzyme an
adequate analgesic effect will not be obtained. Estimates indicate that up to 7% of the
Caucasian population may have this deficiency. However, if the patient is an
extensive or ultra-rapid metaboliser there is an increased risk of developing side
effects of opioid toxicity even at commonly prescribed doses. These patients convert
codeine into morphine rapidly resulting in higher than expected serum morphine
levels.
General symptoms of opioid toxicity include confusion, somnolence, shallow
breathing, small pupils, nausea, vomiting, constipation and lack of appetite. In severe

cases this may include symptoms of circulatory and respiratory depression, which
may be life threatening and very rarely fatal. Estimates of prevalence of ultra-rapid
metabolisers in different populations are summarised below:
Population
African/Ethiopian
African American
Asian
Caucasian
Greek
Hungarian
Northern European

Prevalence %
29%
3.4% to 6.5%
1.2% to 2%
3.6% to 6.5%
6.0%
1.9%
1% to 2%

Post operative use in children
There have been reports in the published literature that codeine given post-operatively
in children after tonsillectomy and/or adenoidectomy for obstructive sleep apnoea, led
to rare, but life threatening adverse events including death (see also section 4.3). All
children received doses of codeine that were within the appropriate dose range;
however there was evidence that these children were either ultra-rapid or extensive
metabolisers in their ability to metabolise codeine to morphine.
Children with compromised respiratory function
Codeine is not recommended for use in children in whom respiratory function might
be compromised including neuromuscular disorders, severe cardiac or respiratory
conditions, upper respiratory or lung infections, multiple trauma or extensive surgical
procedures. These factors may worsen symptoms of morphine toxicity.

4.5

Interaction with other medicinal products and other forms of interaction
The speed of absorption of paracetamol may be increased by metoclopramide or
domperidone and absorption reduced by cholestyramine.
The anticoagulation effect of warfarin and other coumarins may be enhanced by
prolonged regular use of paracetamol with increased risk of bleeding; occasional
doses have no significant effect.
Codeine may delay the absorption of mexiletine and thus reduce the antiarrhythmic
effect of the latter. The depressant effects of codeine are enhanced by depressants of
the central nervous system such as hypnotics, sedatives, tricyclic antidepressants and
phenothiazines.
Codeine may antagonise the gastrointestinal effects of
metoclopramide and domperidone.

4.6

Fertility, pregnancy and lactation
The safety of paracetamol and codeine tablets during pregnancy has not been
established and in view of the possible association of codeine with respiratory
depression and heart malformations, use during this period should be avoided.

Codeine should not be used during breastfeeding (see section 4.3).
At normal therapeutic doses codeine and its active metabolites may be present in
breast milk at very low doses and is unlikely to adversely affect the breast fed infant.
However, if the patient is an ultra-rapid metaboliser of CYP2D6, higher levels of the
active metabolite, morphine, may be present in breast milk and on very rare occasions
may result in symptoms of opioid toxicity in the infant, which may be fatal.
Paracetamol is excreted in breast milk but not in a clinically significant amount.
Available published data do not contraindicate breast feeding.

4.7

Effects on ability to drive and use machines
No adverse effects known.

4.8

Undesirable effects
The most common side effects are nausea, vomiting, constipation, dry mouth,
sweating, skin rashes and other allergic reactions. There have been reports of blood
dyscrasias including thrombocytopenia and agranulocytosis, but these were not
necessarily causally related to paracetamol.
Regular prolonged use of codeine is known to lead to addiction and symptoms of
restlessness and irritability may result when treatment is then stopped.
Prolonged use of a painkiller for headaches can make them worse.
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

Paracetamol
Liver damage is possible in adults who have taken 10g or more of paracetamol.
Ingestion of 5g or more of paracetamol may lead to liver damage if the patient
has risk factors (see below).
Risk Factors:
If the patient
a) Is on long term treatment with carbamazepine, phenobarbitone, phenytoin,
primidone, rifampicin, St John’s Wort or other drugs that induce liver
enzymes.

or
b) Regularly consumes ethanol in excess of recommended amounts.
or
c) Is likely to be glutathione deplete e.g. eating disorders, cystic fibrosis, HIV
infection, starvation, cachexia.
Symptoms
Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea,
vomiting, anorexia and abdominal pain. Liver damage may become apparent
12 to 48 hours after ingestion. Abnormalities of glucose metabolism and
metabolic acidosis may occur. In severe poisoning, hepatic failure may
progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema
and death. Acute renal failure with acute tubular necrosis, strongly suggested
by loin pain, haematuria and proteinuria, may develop even in the absence of
severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.
Management
Immediate treatment is essential in the management of paracetamol
overdosage. Despite a lack of significant early symptoms, patients should be
referred to hospital urgently for immediate medical attention. Symptoms may
be limited to nausea or vomiting and may not reflect the severity of overdose
or the risk of organ damage. Management should be in accordance with
established treatment guidelines, see BNF overdose section.
Treatment with activated charcoal should be considered if the overdose has
been taken within 1 hour. Plasma paracetamol concentration should be
measured at 4 hours or later after ingestion (earlier concentrations are
unreliable) but results should not delay initiation of treatment beyond 8 hours
after ingestion, as the effectiveness of the antidote declines sharply after this
time. If required the patient should be given intravenous N-acetylcysteine, in
line with the established dosage schedule. If vomiting is not a problem, oral
methionine may be a suitable alternative for remote areas, outside hospital.

Codeine
The effects of codeine in overdosage will be potentiated by simultaneous
ingestion of alcohol and psychotropic drugs.
Central nervous system depression, including respiratory depression, may
develop but is unlikely to be severe unless other sedative agents have been coingested, including alcohol, or the overdose is very large. The pupils may be
pin-point in size; nausea and vomiting are common. Hypotension and
tachycardia
are
possible
but
unlikely.
Management should include general symptomatic and supportive measures
including a clear airway and monitoring of vital signs until stable. Consider

activated charcoal if an adult presents within one hour of ingestion of more
than 350mg or a child more than 5mg/kg.
Give naloxone if coma or respiratory depression is present. Naloxone is a
competitive antagonist and has a short half-life so large and repeated doses
may be required in a seriously poisoned patient. Observe for at least 4 hours
after ingestion.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Paracetamol is a peripherally acting analgesic with antipyretic activity.
Codeine is a centrally acting weak analgesic. Codeine exerts its effect through
µ opioid receptors, although codeine has low affinity for these receptors, and
its analgesic effect is due to its conversion to morphine. Codeine, particularly
in combination with other analgesics such as paracetamol, has been shown to
be effective in acute nociceptive pain.

5.2

Pharmacokinetic properties

Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma
concentrations occurring about 30 minutes to 2 hours after ingestion. Paracetamol is
metabolised in the liver and excreted in the urine mainly as the glucuronide and
sulphate conjugates, with about 10% as glutathione conjugates. Less than 5% is
excreted as unchanged paracetamol. The elimination half life varies from about 1-4
hours.

Plasma protein binding is negligible at usual therapeutic concentrations,

although this is dose dependent.

Codeine phosphate is absorbed from the gastrointestinal tract and peak plasma
concentrations occur after about one hour. Codeine is metabolised by O- and
N-Demethylation in the liver to morphine and norcodeine. Codeine and its
metabolites are excreted almost entirely by the kidney, mainly as conjugates
with glucuronic acid. The plasma half life has been reported to be between 3
and 4 hours.

5.3

Preclinical safety data
Not applicable.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Pregelatinised maize starch
Maize starch pdr
Microcrystalline cellulose
Purified water
Dried maize starch pdr
Magnesium stearate
Sodium metabisulphite

BP
BP
Ph Eur
PhEur
BP
Ph Eur
BP

6.2

Incompatibilities
None stated.

6.3

Shelf life
60 months in glass bottle
36 months in HDPE bottle
18 months in blister

6.4

Special precautions for storage
None.

6.5

Nature and contents of container
Amber glass bottle fitted with a child resistant polythene/polypropylene cap
fitted with a waxed aluminium faced pulpboard liner or with a tamper evident
lectraseal liner of surlyn/ aluminium/polythene/bleached kraft paper/melinex
coated carton board.
Pack sizes: 25/30/32
or a white HDPE bottle with a polypropylene cap fitted with an induction heat
seal membrane.
Pack sizes: 25/30/32
or a child-resistant push through pack of opaque 250 micron PVC/40gsm
PVdC blisters heat sealed to 35gsm Glassine paper/9 micron soft temper
aluminium foil.
Pack sizes: 6/8/10/12/16/18/20/24/25/30/32

6.6

Special precautions for disposal
Not applicable.

7

MARKETING AUTHORISATION HOLDER
The Boots Company PLC
1 Thane Road West
Nottingham
NG2 3AA

8

MARKETING AUTHORISATION NUMBER(S)
PL 00014/0251

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
9 July 1981 / 28 October 2004

10

DATE OF REVISION OF THE TEXT
05/11/2013

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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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