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CODIS 500

Active substance(s): ASPIRIN / CODEINE PHOSPHATE / ASPIRIN / CODEINE PHOSPHATE / ASPIRIN / CODEINE PHOSPHATE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Codis 500

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Active Ingredients
Aspirin
Codeine phosphate*

mg/Tablet
500.0
8.0

Specification
Ph Eur
Ph Eur

*Equivalent to 6.2mg codeine

3

PHARMACEUTICAL FORM
Dispersible tablet

4.1

Therapeutic indications
Codis 500 (which contains codeine) is indicated in children older than 16 for
the short term treatment of acute, moderate pain which is not considered to be
relieved by other analgesics such as paracetamol, ibuprofen or aspirin alone,
such as headache, muscular aches, rheumatic pain, toothache, period pains) or
acute, moderate pain associated with migraine, neuralgia, sprains, strains,
sciatica, lumbago, fibrositis, and joint swelling.

4.2

Posology and method of administration
For oral administration, after dissolution in water.
Codeine should be used at the lowest effective dose for the shortest period of
time.
Adults:
One to two tablets or as directed, dissolved in water. The dose may be
repeated after 4 hours: maximum eight tablets in 24 hours in divided doses.
Children aged 16-18 years:
One to two tablets or as directed, dissolved in water. The dose may be
repeated after 4 hours: maximum eight tablets in 24 hours in divided doses.
Children aged less than 16 years:

Do not give to children aged under 16 years unless specifically indicated (e.g.
Kawasaki’s disease).
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).

There is no indication that dosage needs to be modified for the elderly.
Not to be taken more frequently than every 4 hours.
The duration of treatment should be limited to 3 days and if no effective pain
relief is achieved the patients/carers should be advised to seek the views of a
physician.
4.3

Contraindications
Not to be given to patients with known allergy to aspirin, suffering from peptic
ulceration or haemophilia.
Not to be used 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)
Not to be used in women during breastfeeding (see section 4.6)
Not to be used in patients for whom it is known they are CYP2D6 ultra-rapid
metabolisers

4.4

Special warnings and precautions for use
There is a possible association between aspirin and Reye’s Syndrome when
given to children. Reye’s Syndrome is a very rarer disease which affects the
brain and liver and can be fatal. For this reason aspirin should not be given to
children aged under 16 years unless specifically indicated (e.g, for Kawasaki’s
disease). If you are receiving regular medical treatment, are asthmatic, allergic
to aspirin or have or have had a stomach ulcer, seek your doctor’s advice
before taking this product.
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
summarized below:
Population
African/Ethiopian

Prevalence %
29%

African American

3.4% to 6.5%

Asian

1.2% to 2%

Caucasian

3.6% to 6.5%

Greek

6.0%

Hungarian

1.9%

Northern European

1%-2%

Post-operative use in children
There have been reports in the published literature that codeine given postoperatively 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 ultrarapid 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.

The label will include:
Front of pack:


Can cause addiction



For three days use only

Back of pack:



For the short term treatment of acute moderate pain when other
painkillers have not worked. Do not take less than four hours after
taking other painkillers



If you need to take this medicine continuously for more than three days
you should see your doctor or pharmacist



This medicine contains codeine which can cause addiction if you take
it continuously for more than three days. If you take this medicine for
headaches for more than three days it can make them worse

The labeling on packs intended for public sale will also include the statement
“Do not give to children aged under 16 years unless on the advice of a doctor”.
The leaflet will include:






Headlines section (to be prominently displayed at the start of the PIL)


For the short term treatment of acute, moderate pain which is not
relieved by paracetamol, ibuprofen or aspirin alone



You should only take this product for a maximum of three days at a
time. If you need to take it for longer than three 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 three 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 three days it
can make them worse

Section 2 : Before taking – Do not take


This medicine contains codeine which can cause addiction if you take
it continuously for more than three 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 three days it can
make them worse

Section 3: Dosage
• (In the dosage warning section): Do not take for more than 3 days. If
you need to use this medicine for more than three 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 three 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.



Section 4: Side effects
• Some people may have side-effects when taking this medicine. If you
have any unwanted side-effects you should seek advice from your
doctor, pharmacist or other healthcare professional. Also you can help
to make sure that medicines remain as safe as possible by reporting any
unwanted side-effects via the internet at www.yellowcard.gov.uk;
alternatively you can call Freephone 0808 100 3352 (available between
10am-2pm Monday – Friday) or fill in a paper form available from
your local pharmacy.
• How do I know if I am addicted?
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 your doctor:

4.5

o

You need to take the medicine for longer periods of time

o

You need to take more than the recommended dose

o

When you stop taking the medicine you feel very unwell but you
feel better if you start taking the medicine again

Interactions with other medicinal products and other forms of interaction
May enhance the effects of anticoagulants and inhibit the effects of
uricosurics.
Experimental data suggest that ibuprofen may inhibit the effect of low dose
aspirin on platelet aggregation when they are dosed concomitantly. However,
the limitations of these data and the uncertainties regarding extrapolation of ex
vivo data to the clinical situation imply that no firm conclusions can be made
for regular ibuprofen use, and no clinically relevant effect is considered to be
likely for occasional ibuprofen use (see section 5.1).

4.6

Pregnancy and lactation
Codeine should not be used during breastfeeding (see section 4.3).
At normal therapeutic doses codeine and its active metabolite 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.

If symptoms of opioid toxicity develop in either the mother or the infant, then
all codeine containing medicines should be stopped and alternative non-opioid
analgesics prescribed. In severe cases consideration should be given to
prescribing naloxone to reverse these effects.
There is clinical and epidemiological evidence for the safety of aspirin in
human pregnancy, but it may prolong labour and contribute to maternal and
neonatal bleeding and is best avoided at term in the last trimester of pregnancy
and during breastfeeding.

4.7

Effects on ability to drive and use machines
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 taking this medicine,
patients should be told:





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 taken to treat a medical or dental problem and
You have taken it according to the information provided with the
medicine and
It was not affecting your ability to drive safely

4.8

Undesirable effects
May precipitate bronchospasm and include attacks of asthma or
hypersensitivity in susceptible subjects, and may include gastrointestinal
hemorrhage, occasionally major.
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.

4.9

Overdose
Codeine
The effects in overdosage will be potentiated by simultaneous ingestion of
alcohol and psychotrophic drugs.
Symptoms

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
This 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 1 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, or 8 hours if a sustained release preparation has been taken.
Salicylates/Aspirin
Salicylate poisoning is usually associated with plasma concentrations
>350mg/L (2.5mmol/L). Most adult deaths occur in patients whose
concentrations exceed 700mg/b (5.1mmol/L). Single doses less than 100mg/kg
are unlikely to cause serious poisoning.
Symptoms
Common features include vomiting, dehydration, tinnitus, vertigo, deafness,
sweating, warm extremities with bounding pulses, increased respiratory rate
and hyperventilation. Some degree of acid-base disturbance is present in most
cases.
A mixed respiratory alkalosis and metabolic acidosis with normal or high
arterial pH (normal or reduced hydrogen ion concentration) is usual in adults
and children over the age of 4 years. In children aged 4 years or less, a
dominant metabolic acidosis with low arterial pH (raised hydrogen ion
concentration) is common. Acidosis may increase salicylate transfer across the
blood brain barrier.
Uncommon features include haematemesis, hyperpyrexia, hypoglycaemia,
hypokalaemia, thrombocytopenia, increased INRIPTR, intravascular
coagulation, renal failure and non-cardiac pulmonary oedema.
Central nervous system features, including confusion, disorientation, coma and
convulsions, are less common in adults than in children.
Management
Give activated charcoal if an adult presents within 1 hour of ingestion of more
than 250mg/kg. The plasma salicylate concentration should be measured,
although the severity of poisoning cannot be determined from this alone, and
the clinical and biochemical features must be taken into account. Elimination
is increased by urinary alkalinisation, which is achieved by the administration
of 1.26% sodium bicarbonate. The urine pH should be monitored. Correct
metabolic acidosis with intravenous
8.4% sodium bicarbonate (first check serum potassium). Forced diuresis
should not be used since it does not enhance salicylate excretion and may
cause pulmonary oedema.

Haemodialysis is the treatment of choice for severe poisoning and should be
considered in patients with plasma salicylate concentrations >700mg/b
(5.1mmoIIL), or lower concentrations associated with severe clinical or
metabolic features. Patients under 10 years or over 70 have increased risk of
salicylate toxicity and may require dialysis at an earlier stage.

5.1

Pharmacodynamic properties
Aspirin
Aspirin inhibits the cyclo-oxygenase enzyme involved in conversion of
phospholipids to prostaglandins and its effect on the body are believed to
result primarily from prevention of prostaglandin production. These effects
include peripheral analgesia, fever reduction, reduction in inflammation and
inhibition of platelet aggregation.
Codeine
Codeine is a centrally acting weak analgesic. Codeine exerts its effects
through µ opioid receptors although codeine has low affinity for these
receptors, and its analgesic effect is due to its conversion to morphine. Its
actions include analgesia, inhibition of the cough reflex and reduction in
gastrointestinal motility. . Codeine, particularly in combination with other
analgesics such as paracetamol, has been shown to be effective in acute
nociceptive pain.

5.2

Pharmacokinetic properties
Aspirin
Aspirin is rapidly absorbed from the stomach and upper gastrointestinal tract
with peak levels after around 20-30 minutes following dissolution. It is subject
to first-pass metabolism with an overall bioavailability of around 70%.
Metabolism is by conversion to salicylic acid and then further to other
metabolites. These are excreted both free and conjugated mainly by the
kidneys. The plasma half-life of aspirin is around 15-20 minutes and of
salicylic acid is 2-3 hours.
Codeine
Codeine is well absorbed from the gastrointestinal tract with peak
concentrations occurring after around 1 hour. Absorption is rapid and virtually
complete with a bioavailability of around 60%. It is metabolised in the liver
and excreted mainly in the urine as free and conjugated metabolites. The halflife of codeine in plasma is 2.5-4 hours.

5.3

Preclinical safety data
No preclinical findings of relevance to the prescriber have been reported.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Calcium carbonate
Maize starch
Citric acid
Talc
Sodium lauryl sulphate
Saccharin

6.2

Incompatibilities
None known

6.3

Shelf life
Three years

6.4

Special precautions for storage
Store below 30°C in a dry place

6.5

Nature and contents of container
Cardboard carton containing tablets in strips of 30 micron aluminium soft
temper foil with the addition of a 12 micron polyester laminate on the
unprinted side.
Pack sizes: 8, 12, 16, 24, 32 (Those packs in bold are currently marketed)

6.6

Special precautions for disposal
Tablets to be dissolved in water prior to administration

7

MARKETING AUTHORISATION HOLDER
Reckitt Benckiser Healthcare (UK) Limited
Dansom Lane
Hull
HU8 7DS

8

MARKETING AUTHORISATION NUMBER
PL 00063/0012

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
24/04/1995

10

/

16/09/2005

DATE OF REVISION OF THE TEXT
12/09/2014

Expand Transcript

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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