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NUROFEN PLUS

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

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Nurofen Plus

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Active constituents:
Ibuprofen Ph Eur
Codeine phosphate Ph Eur

3

200.0 mg
12.8 mg

PHARMACEUTICAL FORM
Tablet

4.1

Therapeutic indications

Nurofen Plus (which contains codeine) is indicated in patients older than 12
years of age for the short term treatment of acute, moderate pain (such as
rheumatic and muscular pain, backache, migraine, headache, neuralgia, period
pain and dental pain) which is not considered to be relieved by other
analgesics such as paracetamol, ibuprofen or aspirin alone.

4.2

Posology and method of administration
Posology:
Recommended dosage:
Adults, the elderly and children over 12 years of age:
One or two tablets every four to six hours.
Children aged 12-18 years:

One or two tablets every four to six hours.
Children under 12 years:
Nurofen plus (which contains 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:
No special dosage modifications are required for elderly patients, unless renal
or hepatic function is impaired, in which case dosage should be assessed
individually.
Do not take more than 6 tablets in 24 hours.
Leave at least four hours between doses and do not take more than 1200mg in
any 24 hour period.
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.
For short term use only. Codeine should be used at the lowest effective dose
for the shortest period of time necessary to relieve symptoms. The patient
should consult a doctor if symptoms persist or worsen, or if the product is
required for more than 3 days.
Method of administration
For oral administration
4.3

Contraindications
Hypersensitivity to Ibuprofen, Codeine or to any of the constituents listed in
section 6.1.
Patients who have previously shown hypersensitivity reactions (e.g. asthma,
rhinitis, angioedema or urticaria) in response to Acetylsalicylic Acid (aspirin)
or other non-steroidal anti-inflammatory drugs (NSAIDs).
Active or history of recurrent peptic ulcer/haemorrhage (two or more distinct
episodes of proven ulceration or bleeding).
History of gastrointestinal bleeding or perforation, related to previous NSAIDs
therapy.
Severe hepatic failure, renal failure or heart failure (See section 4.4, Special
warnings and precautions for use).
Last trimester of pregnancy (See section 4.6 Pregnancy and lactation).
In women during breastfeeding (see section 4.6)
Respiratory depression.
Chronic constipation

Concomitant treatment with Monoamine Oxidase Inhibitors (MAOIs) or
within 14 days of stopping treatment (see section 4.5).
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 patients for whom it is known they are CYP2D6 ultra-rapid metabolisers

4.4

Special warnings and precautions for use
Undesirable effects may be minimised by using the lowest effective dose for
the shortest duration necessary to control symptoms (see GI and
cardiovascular risks below).
The elderly are at increased frequency of adverse reactions to NSAIDS,
especially gastrointestinal bleeding and perforation which may be fatal (see
section 4.2).
Respiratory:
Bronchospasm may be precipitated in patients suffering from or with a
previous history of bronchial asthma or allergic disease.
Other NSAIDS:
The use of Nurofen Plus with concomitant NSAIDS including
cyclooxygenase-2-selective inhibitors should be avoided (see section 4.5).
SLE and mixed connective tissue disease:
Systemic lupus erythematosus and mixed connective tissue disease due to
increased risk of aseptic meningitis (see section 4.8 Undesirable effects).
Renal:
Renal impairment as renal function may further deteriorate (See section 4.3
and Section 4.8). There is a risk of renal impairment in dehydrated children
and adolescents.
Hepatic:
Hepatic dysfunction (See section 4.3 and Section 4.8).
Cardiovascular and cerebrovascular effects:
Caution (discussion with doctor or pharmacist) is required prior to starting
treatment in patients with a history of hypertension and/or heart failure as fluid
retention, hypertension and oedema have been reported in association with
NSAID therapy.
Clinical trial and epidemiological data suggest that use of ibuprofen,
particularly at high doses (2400 mg daily) and in long-term treatment may be
associated with a small increased risk of arterial thrombotic events (for
example myocardial infarction or stroke). Overall, epidemiological studies do

not suggest that low dose ibuprofen (e.g. ≤ 1200 mg daily) is associated with
an increased risk of myocardial infarction.
Nurofen Plus tablets should be used with caution in those with hypotension
and/ or hypothyroidism. The tablets should be used with caution in patients
with raised intracranial pressure or head injury.

Impaired female fertility:
There is limited evidence that drugs which inhibit cyclo-oxygenase/
prostaglandin synthesis may cause impairment of female fertility by an effect
on ovulation. This is reversible upon withdrawal of treatment.
Gastrointestinal effects:
NSAIDs should be given with care to patients with a history of gastrointestinal
disease (ulcerative colitis, Crohn’s disease) as these conditions may be
exacerbated (See section 4.8 Undesirable effects).
Gastrointestinal bleeding, ulceration or perforation, which can be fatal, has
been reported with all NSAIDs at anytime during treatment, with or without
warning symptoms or a previous history of serious GI events.
The risk of GI bleeding, ulceration or perforation is higher with increasing
NSAID doses, in patients with a history of ulcer, particularly if complicated
with haemorrhage or perforation (see section 4.3), and in the elderly. These
patients should commence treatment on the lowest dose available.
Patients with a history of GI toxicity, particularly when elderly, should report
any unusual abdominal symptoms (especially GI bleeding) particularly in the
initial stages of treatment.
Caution should be advised in patients receiving concomitant medications
which could increase the risk of gastrotoxicity, ulceration or bleeding, such as
oral corticosteroids, or anticoagulants such as warfarin, selective serotonin
reuptake inhibitors or anti-platelet agents such as Acetylsalicylic Acid
(aspirin) (see section 4.5 Interactions).
When GI bleeding or ulceration occurs in patients receiving ibuprofen, the
treatment should be withdrawn.
Dermatological effects:
Serious skin reactions, some of them fatal, including exfoliative dermatitis,
Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported
very rarely in association with the use of NSAIDs (see section 4.8). Patients
appear to be at highest risk of these reactions early in the course of therapy,
the onset of the reaction occurring in the majority of cases within the first
month of treatment. Nurofen PLUS should be discontinued at the first
appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Do not take concurrently with any other Codeine containing compounds.
Care is advised in the administration of Codeine to patients with hypotension,
hypothyroidism, adrenocortical insufficiency, shock, obstructive bowel
disorders, acute abdominal conditions (e.g. peptic ulcer), recent astrointestinal
surgery, gallstones, myasthenia gravis, a history of peptic ulcer or convulsions
and also in patients with a history of drug abuse.
Elderly patients may metabolise or eliminate opioid analgesics more slowly
than younger adults. Codeine should be used with caution in the elderly and
debilitated patients as they may be more susceptible to the respiratory
depressant effects.
Prolonged regular use of Codeine, except under medical supervision, may lead
to physical and psychological dependence (addiction) and result in withdrawal
symptoms, such as restlessness and irritability once the drug is stopped.
If you are pregnant or are being prescribed medicines by your doctor, seek this
advice before taking this product. Care is advised in the administration of this
product in patients with severe renal or severe hepatic impairment (hepatic
disease).
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

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:


List of indications as agreed in 4.1 of the SmPC



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



Read the enclosed leaflet before taking this product.
Do not take if you
• have (or have had two or more episodes of) a stomach ulcer, perforation
or bleeding
• are allergic to ibuprofen or any other ingredient of the product, aspirin or
other related painkillers
• are taking other NSAID painkillers, or aspirin with a daily dose above
75mg
• are breastfeeding
Speak to a pharmacist or your doctor before taking this product if you
• have or have had asthma , diabetes, high cholesterol, high blood pressure,
a stroke, liver, heart, kidney or bowel problems
• are a smoker
• are pregnant

If symptoms persist or worsen, consult your doctor.

The leaflet will include:


Headlines section (to be prominently displayed at the start of the PIL)
• This medicine can only be used for …….(indications)
• 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): This medicine should not be taken for
more than 3 days. If the pain does not improve after 3 days, talk to
your doctor for advice.
• 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:
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

4.5

Interaction with other medicinal products and other forms of interaction
The following drug-drug interactions are known to occur in association with
the Ibuprofen active substance in the product:
Ibuprofen should be avoided in combination with:
Acetylsalicylic Acid (Aspirin): Unless low-dose acetylsalicylic acid (aspirin)
(not above 75mg daily) has been advised by a doctor, as this may increase the
risk of adverse reactions (See section 4.4).
Experimental data suggest that ibuprofen may inhibit the effect of low dose
Acetylsalicylic Acid (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).
Other NSAIDS including cyclooxygenase-2 selective inhibitors: Avoid
concomitant use of two or more NSAIDs as this may increase the risk of
adverse effects (see section 4.4).
Ibuprofen should be used with caution in combination with:
Anticoagulants: NSAIDS may enhance the effects of anti-coagulants, such as
warfarin (See section 4.4).
Antihypertensives (ACE inhibitors and Angiotensin II Antagonists) and
diuretics: NSAIDs may diminish the effect of these drugs. In some patients
with compromised renal function (e.g. dehydrated patients or elderly patients
with compromised renal function) the coadministration of an ACE inhibitor or
Angiotensin II antagonist and agents that inhibit cyclo-oxygenase may result
in further deterioration of renal function, including possible acute renal failure,
which is usually reversible. These interactions should be considered in patients
taking a coxib concomitantly with ACE inhibitors or angiotensin II
antagonists. Therefore, the combination should be administered with caution,
especially in the elderly. Patients should be adequately hydrated and
consideration should be given to monitoring of renal function after initiation of
concomitant therapy, and periodically thereafter. Diuretics can increase the
risk of nephrotoxicity of NSAIDs.
Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding (See
section 4.4 Special warnings).
Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs):
increased risk of gastrointestinal bleeding (see section 4.4).

Cardiac glycosides: NSAIDS may exacerbate cardiac failure, reduce GFR and
increase plasma glycoside levels.
Lithium: There is evidence for potential increases in plasma levels of lithium.
Methotrexate: There is a potential for an increase in plasma methotrexate.
Ciclosporin: Increased risk of nephrotoxicity.
Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone
administration as NSAIDs can reduce the effect of mifepristone.
Tacrolimus; Possible increased risk of nephrotoxicity when NSAIDs are given
with tacrolimus.
Zidovudine: Increased risk of hematological toxicity when NSAIDs are given
with zidovudine. There is evidence of an increased risk of haemarthroses and
haematoma in HIV (+) haemophiliacs receiving concurrent treatment with
zidovudine and ibuprofen.
Quinolone antibiotics: Animal data indicate that NSAIDs can increase the risk
of convulsions associated with quinolone antibiotics. Patients taking NSAIDs
and quinolones may have an increased risk of developing convulsions.
The following drug-drug interactions are known to occur in association
with the Codeine active substance in the product:













Monoamine Oxidase Inhibitors (MAOIs): CNS depression or
excitation may occur if Codeine is given to patients receiving
monoamine oxidase inhibitors, or within two weeks of stopping
treatment with them.
Moclobemide: Risk of hypertensive crisis.
Hydroxyzine: Concurrent use of hydroxyzine (anxiolytics) with
Codeine may result in increased analgesia as well as increased CNS
depressant, sedative and hypotensive effects.
Central Nervous System Depressants: The depressant effects of
Codeine are enhanced by depressants of the central nervous system
such as alcohol, anaesthetics, hypnotics, sedatives, tricyclic
antidepressants or antipsychotics and phenothiazines.
Diuretics and Anti-hypertensives: The hypotensive actions of
diuretics and anti-hypertensive agents may be potentiated when used
concurrently with opioid analgesics.
Antidiarrhoeal and Anti-peristaltic agents: Concurrent use of
Codeine with antidiarrhoeal and antiperistaltic agents such as
loperamide and kaolin may increase the risk of severe constipation.
Antimuscarinics: Concomitant use of antimuscarinics or medications
with muscarinic action, e.g. atropine and some antidepressants may
result in an increased risk of severe constipation which may lead to
paralytic ileus and/or urinary retention.
Neuromuscular Blocking Agents: The respiratory depressant effect
caused by neuromuscular blocking agents may be additive to the
central respiratory depressant effects of opioid analgesics.
Quinidine: Quinidine can inhibit the analgesic effect of Codeine.



Mexiletine: Codeine may delay the absorption of mexiletine and thus
reduce the antiarrhythmic effect of the latter.
• Metoclopramide, Cisapride and Domperidone: Codeine may
antagonise the gastrointestinal effects of metoclopramide, cisapride
and domperidone.
• Cimetidine: Cimetidine inhibits the metabolism of opioid analgesics
resulting in increased plasma concentrations.
• Naxolone: Naxolone antagonises the analgesic, CNS and respiratory
depressant effects of opioid analgesics. Naltrexone also blocks the
therapeutic effect of opioids.
• Interference with laboratory tests: Opioid analgesics interfere with a
number of laboratory tests including plasma amylase, lipase, bilirubin,
alkaline phosphatase, lactate dehydrogenase, alanine aminotransferase
and aspartate aminotransferase. Opioids may also interfere with gastric
emptying studies as they delay gastric emptying and with hepatobiliary
imaging using technetium Tc 99m disofenin as opioid treatment may
cause constriction of the sphincter of Oddi and increase biliary tract
pressure.
4.6

Pregnancy and lactation
Pregnancy:
Whilst no teratogenic effects have been demonstrated in animal experiments,
the use of Nurofen Plus should, if possible, be avoided during the first 6
months of pregnancy.
During the last trimester, ibuprofen is contraindicated as there is there is a risk
of premature closure of the foetal ductus arteriosus with possible persistent
pulmonary hypertension. The onset of labour may be delayed and the duration
increased with an increased bleeding tendency in both mother and child. (See
section 4.3 Contraindications).
Breast Feeding:
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 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.
Fertility:
See section 4.4 regarding female fertility.

4.7

Effects on ability to drive and use machines
Patient may become dizzy or sedated with NUROFEN PLUS tablets. Rare
side effects may include convulsions, hallucinations, blurred or double vision
and orthostatic hypotension (see section 4.8). If affected, patients should not
drive or 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 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:
-

4.8

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

Undesirable effects
Hypersensitivity reactions have been reported and these may consist of:
a) Non-specific allergic reactions and anaphylaxis.
b) Respiratory tract reactivity, e.g. asthma, aggravated asthma,
bronchospasm, dyspnoea.
c) Various skin reactions, e.g. pruritus, urticaria, angioedema and more
rarely exfoliative and bullous dermatoses (including epidermal necrolysis
and erythema multiforme). 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 headache can make them worse.
The following list of adverse effects relates to those experienced with
ibuprofen at OTC doses (maximum 1200mg Ibuprofen per day), for short-term
use. In the treatment of chronic conditions, under long-term treatment,
additional adverse effects may occur.
Adverse events which have been associated with Ibuprofen and Codeine are
given below, tabulated by System Organ Class (SOC) and frequency.
Frequencies are defined as: very common (≥1/10), common (≥1/100 and
<1/10), uncommon (≥1/1000 and <1/100), rare (≥1/10,000 and <1/1000), very
rare (< 1/10,000) and not known (cannot be estimated from the available
data). Within each frequency grouping, adverse events are presented in order
of decreasing seriousness.

Cardiovascular and Cerebrovascular:
Oedema, hypertension, and cardiac failure, have been reported in association
with NSAID treatment.
Clinical trial and epidemiological data suggest that use of ibuprofen
(particularly at high doses 2400mg daily) and in long-term treatment may be
associated with a small increased risk of arterial thrombotic events (for
example myocardial infarction or stroke) (see section 4.4).

System Organ Class

Frequency

Adverse Events

Blood and Lymphatic
System Disorders

Very rare

Haematopoietic
disorders1

Immune System
Disorders

Uncommon

Hypersensitivity
reactions with urticaria
and Pruritus

Very rare

Severe hypersensitivity
reactions. Symptoms
could be: facial, tongue
and throat swelling,
dyspnoea, tachycardia,
hypotension,
(anaphylaxis,
angioedema or severe
shock)

Metabolism and
Nutrition Disorders

Not known

Decreased appetite

Psychiatric Disorders

Not known

Depression,
hallucination,
confusional state,
dependence, mood
altered, restlessness,
nightmares

Nervous System
Disorders

Uncommon

Headache

Very rare

Aseptic meningitis2

Not known

Dizziness, drowsiness,
convulsion, Intracranial
pressure increased,
headache, dyskinesia.

Eye Disorders

Not known

Vision blurred, diplopia

Ear and Labyrinth
disorders

Not known

Vertigo

Cardiac Disorders

Not known

Vascular Disorders

Not known

Cardiac failure, oedema,
bradycardia,
palpitations3
Hypertension, orthostatic
hypotension3

Respiratory, Thoracic
and
Mediastinal Disorders

Not known

Respiratory tract
reactivity comprising
asthma,
bronchospasm or
dyspnoea
Respiratory depression,
cough suppression

Gastrointestinal
Disorders

Uncommon

Abdominal pain, nausea
and dyspepsia4

Rare

Diarrhoea, flatulence,
constipation and
vomiting

Very rare

Peptic ulcer,
gastrointestinal
perforation or
gastrointestinal
haemorrhage, melaena,
and haematemesis5.
Mouth ulceration and
gastritis.
Exacerbation of
ulcerative colitis and
Crohn’s disease6

Not known

Dry mouth

Very rare

Liver disorder

Not known

Biliary colic

Uncommon

Various skin rashes

Very rare

Severe forms of skin
reactions such as bullous

Hepatobiliary Disorders

Skin and Subcutaneous
Tissue Disorders

reactions, including
Stevens-Johnsons
Syndrome, erythema
multiforme and toxic
epidermal necrolysis can
occur
Not known

Flushing

Musculoskeletal and
Connective Tissue
Disorders

Not known

Muscle rigidity

Renal and Urinary
Disorders

Very rare

Acute renal failure7

Not known

Ureteric colic, dysuria8

General and
Administration Site
Conditions

Not known

Hypothermia,
hyperhidrosis,
irritability, fatigue,
malaise

Investigations

Very rare

Haemoglobin decreased

Description of Selected Adverse Reactions
1
Examples include anaemia, leucopenia, thrombocytopenia, pancytopenia and
agranulocytosis. First signs are: fever, sore throat, superficial mouth ulcers,
flu-like symptoms, severe exhaustion, unexplained bleeding and bruising.
2

Single cases have been reported very rarely. The pathogenic mechanism of
drug-Induced aseptic meningitis is not fully understood. However, the
available data on NSAID-related aseptic meningitis points to a
hypersensitivity reaction (due to a temporal relationship with drug intake, and
disappearance of symptoms after drug discontinuation). In patients with
existing auto-immune disorders (such as systemic lupus erythematosus, mixed
connective tissue disease) during treatment with ibuprofen, single cases of
symptoms of aseptic meningitis, such as stiff neck, headache, nausea,
vomiting, fever or disorientation have been observed (see section 4.4).

3

Reported in association with NSAID treatment. Clinical trial and
epidemiological data suggest that use of ibuprofen (particularly at high doses
2400mg daily) and in long-term treatment may be associated with a small
increased risk of arterial thrombotic events (for example myocardial infarction
or stroke) (see section 4.4).

4

The most commonly-observed adverse events are gastrointestinal in nature.

5

Sometimes fatal, particularly in the elderly.

6

See section 4.4.

7

Especially in long-term use, associated with increased serum urea and
oedema. Also includes papillary necrosis.
8

Increased frequency, decrease in amount.

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 national reporting system.

4.9

Overdose
Overuse of this product, defined as consumption of quantities in excess of the
recommended dose, or consumption for a prolonged period, may lead to
physical or psychological dependency. Symptoms of restlessness and
irritability may result when treatment is stopped.
Symptoms of overdose with ibuprofen include;
In children ingestion of more than 400 mg/kg may cause symptoms. In adults
the dose response effect is less clear cut. The half-life in overdose is 1.5-3
hours.
Symptoms
Most patients who have ingested clinically important amounts of NSAIDs will
develop no more than nausea, vomiting, epigastric pain, or more rarely
diarrhoea. Tinnitus, headache and gastrointestinal bleeding are also possible.
In more serious poisoning, toxicity is seen in the central nervous system,
manifesting as drowsiness, occasionally excitation and disorientation or coma.
Occasionally patients develop convulsions. In serious poisoning metabolic
acidosis may occur and the prothrombin time/ INR may be prolonged,
probably due to interference with the actions of circulating clotting factors.
Acute renal failure and liver damage may occur. Exacerbation of asthma is
possible in asthmatics.
Management
Management should be symptomatic and supportive and include the
maintenance of a clear airway and monitoring of cardiac and vital signs until
stable. Consider oral administration of activated charcoal if the patient
presents within 1 hour of ingestion of a potentially toxic amount. If frequent or
prolonged, convulsions should be treated with intravenous diazepam or
lorazepam. Give bronchodilators for asthma.
Symptoms of overdose with codeine include;
Nausea and vomiting are prominent features. Respiratory depression,
excitability, convulsions, hypotension and loss of consciousness may occur
with large codeine overdose.

The stomach should be emptied. If severe CNS depression has occurred,
artificial respiration, oxygen and parenteral naloxone may be needed.
Imbalance in electrolyte levels should be considered.

5.1

Pharmacodynamic properties
Pharmacotherapeutic Group: Ibuprofen, combinations; ATC Code: M01
AE51
Ibuprofen is a propionic acid derivative NSAID that has demonstrated its
efficacy by inhibition of prostaglandin synthesis. In humans ibuprofen reduces
inflammatory pain, swelling and fever. Furthermore, ibuprofen reversibly
inhibits platelet aggregation.
Codeine is a centrally acting weak narcotic analgesic. Codeine exerts its
effects through μ opioid receptors, and its analgesic effect is due to its
conversion to morphine. The combination of a well tolerated peripheral
analgesic with a centrally acting analgesic provides optimum pain relief with a
lower potential for producing side effects. Codeine, particularly in
combination with other analgesics such as paracetamol, has been shown to be
effective in acute nociceptive pain.
Experimental data suggest that ibuprofen may inhibit the effect of low dose
aspirin on platelet aggregation when they are dosed concomitantly. In one
study, when a single dose of ibuprofen 400mg was taken within 8 h before or
within 30 min after immediate release aspirin dosing (81mg), a decreased
effect of ASA on the formation of thromboxane or platelet aggregation
occurred. 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.

5.2

Pharmacokinetic properties
The elimination half-life of both ibuprofen and codeine is approximately three
hours, and both drugs are given three to fours times daily. The combination of
the two drugs is therefore appropriate from a pharmacokinetic viewpoint; the
tablet exhibits normal release characteristics for both active substances.

5.3

Preclinical safety data
Not applicable.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Tablet core:
Microcrystalline cellulose, Sodium starch glycollate, Starch pregelatinised,
Hypromellose
Film coating:
Hypromellose Ph Eur
Opaspray White M-1-17111B
Talc Ph Eur

6.2

Incompatibilities
None known.

6.3

Shelf life
36 months.

6.4

Special precautions for storage
Store in a dry place below 25ºC.

6.5

Nature and contents of container
Blister packs containing 6, 8, 12, 16, 18, 24 or 32 tablets.

6.6

Special precautions for disposal
Not applicable.

7

MARKETING AUTHORISATION HOLDER
Reckitt Benckiser Healthcare (UK) Ltd
Slough
SL1 4AQ

8

MARKETING AUTHORISATION NUMBER(S)
PL 00063/0376

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
16 May 1994 / 19 September 2008

10

DATE OF REVISION OF THE TEXT
12/09/2017

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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