Co-codamol 8 / 500 effervescent tablets (POM)

1. Name Of The Medicinal Product

Co-codamol 8/500 Effervescent Tablets

2. Qualitative And Quantitative Composition

Each effervescent tablet contains 500mg paracetamol and 8mg codeine phosphate.

Also contains sorbitol and sodium (see section 4.4)

For a full list of excipients, see section 6.1

3. Pharmaceutical Form

Effervescent Tablet

Flat white tablets with bevelled edges

4. Clinical Particulars

4.1 Therapeutic Indications

For the relief of most painful and febrile conditions such as headache including migraine, neuralgia, toothache, sore throat, colds, influenza, dysmenorrhoea and rheumatic pain.

4.2 Posology And Method Of Administration

Adults and children over 12 years:

Two tablets, to be dissolved in water, not more frequently than every 4 hours, up to a maximum of 8 tablets in any 24 hour period.

Children under 12 years:

Not recommended for children under 12 years of age.

The product is for oral administration.

4.3 Contraindications

Hypersensitivity to paracetamol, codeine phosphate or any of the other constituents.

4.4 Special Warnings And Precautions For Use

Care is advised in the administration of paracetamol to patients with severe renal or severe hepatic impairment. The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease.

This product contains 388mg of sodium per effervescent tablet. This may be harmful to people on a low sodium or low salt diet.

This product contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.

The recommended dose should not be exceeded. This medicine should not be taken with any other paracetamol-containing products. If symptoms persist, the patient should be advised to consult their doctor. The patient should be advised to see immediate medical advice in the event of an overdose, even if they feel well, because of the risk of delayed, serious liver damage.

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

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 ultra-rapid 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 while breast feeding as the levels of the active ingredients of this medicine 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 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

The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine. The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular daily use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.

4.6 Pregnancy And Lactation

Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol used in the recommended dose. Codeine has been used for many years without apparent ill consequence and animal studies have not shown any hazard. Patients should follow the advice of their doctor regarding the use of this product.

Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breast feeding.

At normal therapeutic doses codeine and its active metabolites may be present in breast milk at very low doses and are 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

None.

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.

Blood and the lymphatic system

Frequency not known: blood dyscrasias including thrombocytopenia and agranulocytosis

Nervous system disorders

Frequency not known: dizziness, light-headedness, confusion, drowsiness

Gastrointestinal disorders

Frequency not known: pancreatitis, constipation, nausea, vomiting

Skin and subcutaneous tissue disorders

Frequency not known: allergic reactions (hypersensitivity) including skin rash

Renal and urinary disorders

Frequency not known: urinary retention

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:

• is on long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St. John's Wort or other drugs that induce liver enzymes, or

• regularly consumes ethanol in excess of recommended amounts, or

• 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 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 at 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 serious hepatic dysfunction beyond 24h from ingestion should be discussed with the NPIS or a liver unit.

Codeine

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 co-ingested, 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 characoal 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 four hours after ingestion, or eight hours if a sustained release preparation has been taken.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Anilides, Paracetamol combinations

ATC Code: N02B E51

Paracetamol is a well established analgesic and antipyretic.

Codeine phosphate is a moderate analgesic and also has a weak cough suppressant activity.

5.2 Pharmacokinetic Properties

Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. Concentration in plasma reaches a peak in 30-60 minutes. Plasma half-life is 1-4 hours. Paracetamol is relatively uniformly distributed throughout most body fluids, plasma protein binding is variable.

Codeine phosphate is well absorbed after oral administration and is widely distributed. About 86% is excreted in the urine in 24 hours, 40-70% is free or conjugated morphine and 10-20% is free or conjugated Norcodeine.

5.3 Preclinical Safety Data

There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Sorbitol,

Saccharin sodium

Sodium hydrogen carbonate (sodium bicarbonate),

Polyvidone (povidone)

Sodium lauryl sulphate

Anhydrous citric acid

Anhydrous sodium carbonate

Dimeticone (dimethicone)

6.2 Incompatibilities

None.

6.3 Shelf Life

48 months.

6.4 Special Precautions For Storage

This medicinal product does not require any special storage conditions.

6.5 Nature And Contents Of Container

Individually packed into PPFP or Surlyn laminate strips in cardboard carton.

Pack sizes: 48, 60, 100.

6.6 Special Precautions For Disposal And Other Handling

No special requirements

7. Marketing Authorisation Holder

Winthrop Pharmaceuticals UK Limited

One Onslow Street

Guildford

Surrey

GU1 4YS

8. Marketing Authorisation Number(S)

PL 17780/0511

9. Date Of First Authorisation/Renewal Of The Authorisation

15 January 2010

10. Date Of Revision Of The Text

02 February 2011

LEGAL CATEGORY

POM