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CO-CODAMOL 30/500 EFFERVESCENT TABLETS

Active substance: PARACETAMOL

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Co-codamol 30/500 Effervescent Tablets.

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 500mg paracetamol and 30mg codeine phosphate hemihydrate.
Excipients with known effect:
Each tablet contains 50mg of sorbitol and 10mg of saccharin sodium.
For the full list of excipients, see section 6.1

3.

PHARMACEUTICAL FORM
Effervescent Tablets.
White bevelled-edge tablets, scored on one face.

4.1

Therapeutic indications
For the relief of severe pain.
Codeine is indicated in patients older than 12 years of age for the treatment of
acute moderate pain which is not considered to be relieved by other analgesics
such as paracetamol or ibuprofen (alone).

4.2

Posology and method of administration
Posology
Adults:

Elderly:

Two tablets not more frequently than every 4 hours, up to a
maximum of 8 tablets in any 24 hour period.
As for adults, however a reduced dose may be required. See
warnings.

Paediatric population
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 section 4.3 and 4.4).
Method of administration
For oral administration.

4.3

Contraindications







4.4

Hypersensitivity to paracetamol, codeine or any of the other constituents.
Conditions where morphine and opioids are contraindicated eg, acute
asthma, respiratory depression, acute alcoholism, head injuries, raised
intra-cranial pressure and following biliary tract surgery; monoamine
oxidase inhibitor therapy, concurrent or within 14 days.
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

Special warnings and precautions for use
Each tablet of the soluble formulation contains 388mg sodium
(16.87mEquivalents). This sodium content should be taken into account when
prescribing for patients in whom sodium restriction is indicated.
Care should be observed in administering the product to any patient whose
condition may be exacerbated by opioids, particularly the elderly, who may be
sensitive to their central and gastro-intestinal effects, those on concurrent CNS
depressant drugs, those with prostatic hypertrophy and those with
inflammatory or obstructive bowel disorders. Care should also be observed if
prolonged therapy is contemplated.
Care is advised in the administration of paracetamol to patients with severe
renal or severe hepatic impairment. The hazards of overdose are greater in
those with alcoholic liver disease.
Patients should be advised not to exceed the recommended dose and not take
other paracetamol containing products concurrently.
The risk-benefit of continued use should be assessed regularly by the
prescriber.
The leaflet will state in a prominent position in the 'before taking' section:
• Do not take for longer than directed by your prescriber
• Taking codeine regularly for a long time can lead to addiction, which
might cause you to feel restless and irritable when you stop the tablets.
• Taking a painkiller for headaches too often or for too long can make them
worse.
The label will state (To be displayed prominently on outer pack – not boxed):
Do not take for longer than directed by your prescriber as taking codeine
regularly for a long time can lead to addiction.
CYP2D6 metabolism

Codeine is metabolised by 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 population 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%-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 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

Interactions with other medicinal products and other forms of interaction
Paracetamol may increase the elimination half-life of chloramphenicol. Oral
contraceptives may increase its rate of clearance. The speed of absorption of
paracetamol may be increased by metoclopramide or domperidone and
absorption reduced by colestyramine.

The anticoagulant 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.
The effects of CNS depressants (including alcohol) may be potentiated by
codeine.

4.6

Fertility, pregnancy and lactation
There is inadequate evidence of the safety of codeine in human pregnancy, but
there is epidemiological evidence for the safety of paracetamol. Both substances
have been used for many years without apparent ill consequences and animal
studies have not shown any hazard. Nonetheless careful consideration should be
given before prescribing the products for pregnant patients. Opioid analgesics
may depress neonatal respiration and cause withdrawal effects in neonates of
dependent mothers.
Paracetamol is excreted in breast milk but not in a clinically significant amount.
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.

4.7

Effects on ability to drive and to use machines
Patients should be advised not to drive or operate machinery if affected by dizziness or
sedation.
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:
• 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

4.8

Undesirable effects




Regular prolonged use of codeine is known to lead to addiction and
tolerance. Symptoms of restlessness and irritability may result when
treatment is then stopped.
Prolonged use of a painkiller for headaches can make them worse.

The information below lists reported adverse reactions, ranked using the
following frequency classification:
Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to
<1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known
(cannot be estimated from the available data).
Codeine can produce typical opioid effects including constipation, nausea,
vomiting, dizziness, light-headedness, confusion, drowsiness and urinary
retention. The frequency and severity are determined by dosage, duration of
treatment and individual sensitivity. Tolerance and dependence can occur,
especially with prolonged high dosage of codeine.
There have been very rare occurrences of pancreatitis.
Immune system disorders
Hypersensitivity including skin rash may occur.
Blood and the lymphatic system
Not known: blood dyscrasias including thrombocytopenia and agranulocytosis
Skin and subcutaneous tissue disorders
Very rare cases of serious skin reactions have been reported
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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9.


Overdose
Nausea and vomiting are prominent symptoms of codeine toxicity and if there
is evidence of circulatory and respiratory depression, suggested treatment is
gastric lavage and catharsis. If CNS depression is severe, assisted ventilation,
oxygen and parenteral naloxone may be needed.
Patients in whom oxidative liver enzymes have been induced, including
alcoholics and those receiving barbiturates and patients who are chronically
malnourished, may be particularly sensitive to the toxic effects of paracetamol
in overdose.

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, coma and death. Acute renal failure with acute
tubular necrosis may develop even in the absence of severe liver damage.
Cardiac arrhythmias and pancreatitis have been reported.
Liver damage is likely in adults who have taken 10g or more of paracetamol. It
is considered that excess quantities of a toxic metabolite (usually adequately
detoxified by glutathione when normal doses of paracetamol are ingested),
become irreversibly bound to liver tissue.
Immediate treatment is essential in the management of paracetamol overdose.
Despite a lack of significant early symptoms, patients should be referred to
hospital urgently for immediate medical attention and any patient who had
ingested around 7.5g or more of paracetamol in the preceding 4 hours should
undergo gastric lavage. Administration of oral methionine or intravenous Nacetylcysteine which may have a beneficial effect up to at least 48 hours after
the overdose, may be required. General supportive measures must be
available.

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Paracetamol, combinations excl. Psycholeptics
ATC Code: N02B E51

Paracetamol is an analgesic which acts peripherally, probably by blocking
impulse generation at the bradykinin sensitive chemo-receptors which evoke
pain. Although it is a prostaglandin synthetase inhibitor, the synthetase system in
the CNS rather than the periphery appears to be more sensitive to it. This may
explain paracetamol's lack of appreciable anti-inflammatory activity.
Paracetamol also exhibits antipyretic activity.
Codeine is a centrally acting weak analgesic. Codeine exerts its effect through µ
opioid receptors, although codeine has low affinity for those 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
Following oral administration of two effervescent tablets (ie, a dose of
paracetamol 1000mg and codeine phosphate 60mg) the mean maximum
plasma concentrations of paracetamol and codeine were 20.4 µg/ml and
218.8ng/ml respectively. The mean times to maximum plasma concentrations
were 0.34 hours for paracetamol 0.42 hours for codeine phosphate.

The mean AUC for the 10 hours following administration was 50.0µg.ml -1.h
for paracetamol and 450.0 ng/ml -1.h for codeine.
The bioavailabilities of paracetamol and codeine phosphate when given as the
combination are similar to those when they are given separately.

5.3

Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional
studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic
potential, toxicity to reproduction and development.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Sodium bicarbonate, anhydrous citric acid, anhydrous sodium carbonate,
sorbitol powder, saccharin sodium, povidone, dimethicone, sodium lauryl
sulphate.

6.2

Incompatibilities
Not applicable

6.3

Shelf life
4 years in PPFP strips
3 years in Surlyn laminate strips.

6.4.

Special Precautions for Storage
Do not store above 25°C. Store in the original package.

6.5.

Nature and Contents of Container
PPFP strips in cardboard cartons.
Pack sizes: 4, 12, 30, 60 and 100 tablets.

Surlyn laminate strips in cardboard cartons.
Pack sizes: 4 and 12 tablets.

6.6

Special precautions for disposal
No special requirements

7

MARKETING AUTHORISATION HOLDER
Winthrop Pharmaceuticals UK Limited
One Onslow Street
Guildford
Surrey
GU1 4YS
United Kingdom
Trading as
Winthrop Pharmaceuticals, PO Box 611, Guildford, Surrey, GU1 4YS
Or
Zentiva, One Onslow Street, Guildford, Surrey, GU1 4YS, UK

8.

MARKETING AUTHORISATION NUMBER
PL 17780/0046

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
04/03/2009

10

DATE OF REVISION OF THE TEXT
09/04/2014

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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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