Co-Codamol 30/500mg Effervescent Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Co-codamol 30/500mg Effervescent Tablets.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 30mg codeine phosphate hemihydrate and 500mg paracetamol.
For Excipients see 6.1.
3 PHARMACEUTICAL FORM
Effervescent tablet.
White circular, flat bevelled edge tablet, plain on both sides.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For the relief of severe pain.
4.2 Posology and method of administration
For oral administration only. The tablets should be dissolved in at least half a tumbler of water before taking.
Adults
One to two tablets dissolved in water not more frequently than every 4 hours to a maximum of 8 tablets in any 24-hour period.
Children
Not recommended for use in children under 12 years of age.
Elderly
A reduced dose may be required.
Dosage is adjusted according to a patients response and the severity of the pain, however tolerance to codeine may develop with prolonged use and care should be taken as adverse effects are dose related.
4.3 Contraindications
Sensitivity to codeine or paracetamol or any of the constituents of the tablets.
Conditions where morphine and opioids are contraindicated e.g. acute asthma, respiratory depression, acute alcoholism, head injuries, raised intra-cranial pressure and following biliary tract surgery.
4.4 Special warnings and precautions for use
Other paracetamol containing medication should not be taken when taking Co-codamol Effervescent Tablets.
These tablets contain 438mg sodium per tablet and should be avoided by patients on a low sodium diet.
The tablets contain aspartame and so should not be taken by patients with phenylketonuria.
Care should be taken when prescribing these tablets to patients with severe liver or renal impairment. The hazards of overdose are greater in those with alcoholic liver disease.
Care should be taken when prescribing for elderly patients who can be more susceptible to the opioid effects such as CNS and gastro-intestinal effects. Other susceptible patients include those on concurrent CNS depressent drugs, those with prostatic hypertrophy and those with inflammatory or obstructive bowel disorders.
Caution is advised when taking codeine with monoamine oxidase inhibitor (MAOI) therapy. Co-codamol Effervescent Tablets should not be taken concurrently or within 14 days of MAOI’s.
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/dihydrocodeine (DHC) 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/DHC regularly for a long time can lead to addiction.
Codeine is partially metabolised by CYP2D6. If a patient has a deficiency or is completely lacking this enzyme they will not obtain adequate analgesic effects. Estimates indicate that up to 7% of the caucasian population may have this deficiency. However, if the patient is an ultrarapid metaboliser there is an increased risk of developing side effects of opioid toxicity even at low doses. General symptoms of opioid toxicity include nausea, vomiting, constipation, lack of appetite and somnolence.
In severe cases this may include symptoms of circulatory and respiratory depression. Estimates indicate that up to 1 to 2% of the caucasian population may be ultra-rapid metabolisers.
The leaflet will state in the “Pregnancy and breast-feeding” subsection of section 2 “Before taking your medicine”:
Usually it is safe to take Co-codamol 30/500 while breast feeding as the level of codeine in breast milk are too low to cause your baby any problems. However, some women who are at increased risk of developing side effects at any dose may have higher levels of codeine in their breast milk. If any of the following side effects develop in you or your baby stop taking this medicine and seek immediate medical advice; feeling sick, vomiting, constipation, decreased or lack of appetite, feeling tired or sleeping for longer than normal, and shallow or slow breathing.
4.5 Interaction with other medicinal products and other forms of interaction
Avoid taking Co-codamol Effervescent Tablets with CNS depressants (including other opioid analgesics and alcohol) or other paracetamol containing products.
Paracetamol may increase the elimination half-life of chloramphenicol. Oral contraceptives may increase its rate of clearance. There is increased absorption when taken with metoclopramide or domperidone. Coadministration with colestyramine may reduce absorption.
Patients on anticoagulants may take occasional doses of Co-codamol Effervescent Tablets but the anticoagulant effect of warfarin and coumarins may be enhanced by prolonged regular administration of paracetamol with increased risk of bleeding. Occasional doses have no significant effect.
4.6 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 product for pregnant patients. Opioid analgesics may depress neonatal respiration and cause withdrawal effects in neonates of dependent mothers.
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 metabolites may be present in breast milk and on very rare occasions may result in symptoms of opioid toxicity in the infant.
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.
4.7 Effects on ability to drive and use machines
Patients should be warned not to drive or operate machinery if they become dizzy or sedated while taking Co-codamol Effervescent Tablets.
4.8 Undesirable effects
Co-codamol Effervescent Tablets are generally well tolerated but hypersensitivity reactions including skin rashes may occur. Rare cases of anaphylaxis, angioedema, urticaria, pruritus and fixed drug eruption have been reported with medications containing paracetamol and/or codeine.
There have been reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to co-codamol.
Codeine may sometimes cause typical opioid effects such as vomiting, constipation, nausea, light-headedness, dizziness, confusion, drowsiness and urinary retention. The frequency and severity of these effects are determined by dosage, duration of treatment and individual sensitivity. There have been rare reports of acute pancreatitis in patients taking codeine or codeine/paracetamol combinations.
• Regular prolonged use of codeine/DHC 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.
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
Paracetamol
Liver damage is possible in adults who have taken 10g or more of paracetamol. Ingestion of 5g or more or paracetamol may lead to liver damage if the patient has risk factors (see below).
Risk factors
Risk factors
If the patient
a. Is on long term treatment with carbamazepine, phenobarbital, 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 overdose 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 overdose. 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 4 hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be used up to 24 hours after ingestion of paracetamol, however, the maximum protective effect is obtained up to 8 hours post-ingestion. 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. Management of patients who present with serious hepatic dysfunction beyond 24h from ingestion should be discussed with the NPIS or a liver unit.
Codeine
Nausea and vomiting are prominent symptoms of codeine toxicity, with circulatory and respiratory depression in severe overdose.
The effects in overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic 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 one hour of ingestion of more than 350 mg or a child more than 5 mg/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 four hours after ingestion, or eight hours if a sustained release preparation has been taken.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Paracetamol has antipyretic and analgesic actions with little anti-inflammatory effect. Codeine is an analgesic related to morphine but with only mild sedative effects.
5.2 Pharmacokinetic properties
Paracetamol is rapidly and well absorbed from the intestinal tract after it has left the stomach. Plasma protein binding is low and paracetamol is metabolised in the liver and mainly excreted in the urine as glucuronide and sulphate conjugates. The elimination half-life is 1-3 hours.
Codeine is absorbed from the gastro-intestinal tract and peak plasma-codeine concentrations are found in about one hour. It is metabolised by O- and N-demethylation in the liver to morphine, norcodeine, and other metabolites including normorphine and hydrocodone. Codeine and its metabolites are excreted almost entirely by the kidney, mainly as conjugates with glucuronic acid. The elimination half-life has been reported to be between 3 and 4 hours.
Preclinical safety data
5.3
There are no preclinical data of relevance which are additional to that already included in other sections of the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium hydrogen carbonate
Citric acid anhydrous
Sodium carbonate
Povidone
Simeticone
Sodium saccharin
Aspartame
Polysorbate 80
6.2 Incompatibilities
Not applicable
6.3 Shelf life
3 years
6.4 Special precautions for storage
Do not store above 25°C. Store in the original package.
6.5 Nature and contents of container
Aluminium / Aluminium foil strips
Pack sizes: 30, 32, 56, 60, 84, 90 and 100 tablets.
6.6 Special precautions for disposal
None
7 MARKETING AUTHORISATION HOLDER
Neolab Limited 57 High Street Odiham Hants RG29 1LF
8 MARKETING AUTHORISATION NUMBER(S)
08137/0133
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
02/07/2015
10 DATE OF REVISION OF THE TEXT
02/07/2015