Co-dydramol Tablets

Each tablet contains 500mg paracetamol and 10mg dihydrocodeine tartrate

For excipients see 6.1.

Tablet.

Flat bevelled edge white tablets marked S/8 on one side

For the relief of mild to moderate pain.

For oral administration.

Adults

One to two tablets every four to six hours.

Maximum of eight tablets daily.

Children

Not recommended for children under twelve years of age.

Elderly

One to two tablets every four to six hours.

Maximum of eight tablets daily.

Reduce dosage if renal or hepatic function is impaired.

Co-dydramol Tablets must not be given to patients with respiratory depression, chronic obstructive airways disease, liver disease or hypersensitivity to dihydrocodeine, paracetamol or any of the other constituents.

Dihydrocodeine may bring about histamine release, therefore it should not be given during an asthma attack and it should be administered with due care to persons liable to such attack. The dosage should be reduced in hypothyroidism and in renal insufficiency.

Alcohol should be avoided. When dihydrocodeine is prescribed for chronic use, care should be taken to avoid unnecessary increase in dosage.

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 to 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 dihydrocodeine 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 dihydrocodeine regularly for a long time can lead to addiction.

Dihydrocodeine should be used with caution in patients taking monoamine oxidase inhibitors, CNS depressants or metoclopramide. The speed of absorption of paracetamol may be increased by metoclopramide and domperidone and absorption reduced by cholestyramine.

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.

At normal therapeutic doses there is epidemiological evidence of the safety of paracetamol in pregnancy, but patients should follow the advice of their doctor regarding its use. Dihydrocodeine has been used for many years without apparent ill effects. It should be used with caution in late pregnancy as it may cause respiratory depression in the neonate.

As with all medicines, use should be avoided during the first trimester.

Dihydrocodeine and paracetamol are excreted in breast milk in concentrations too low to be harmful to the breast fed infant.

Dihydrocodeine may cause vertigo which may affect the ability to drive or use machines.

• Regular prolonged use of dihydrocodeine 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.

Dihydrocodeine may cause constipation, nausea, vomiting, headache or vertigo and these are relatively common if the dose is increased above 30mg. If constipation occurs it can be treated with a gentle laxative. Tolerance and dependence may occur with dihydrocodeine especially with prolonged dosage.

There have been very rare occurrences of pancreatitis.

Side effects with paracetamol are rare but rashes and other allergic reactions may occur occasionally. There have been isolated reports of thrombocytopenia, purpura and agranulocytosis.

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.

Dihydrocodeine

Symptoms

Acute overdosage with dihydrocodeine can be manifested by somnolence progressing to stupor or coma, miotic pupils, rhabdomyolysis, non-cardiac pulmonary oedema, bradycardia, hypotension and respiratory depression or apnoea.

Management

Primary attention should be given to the establishment of a patent airway and institution of assisted or controlled ventilation.

In the case of massive overdosage, administer naloxone intravenously (0.4 to 2 mg for an adult and 0.01 mg/kg body weight for children) if the patient is in a coma or respiratory depression is present. Repeat the dose at 2 minute intervals if there is no response, or by an infusion. An infusion of 60% of the initial dose per hour is a useful starting point. A solution of 10 mg made up in 50 ml dextrose will produce 200 micrograms/ml for infusion using an IV pump (dose adjusted to the clinical response). Infusions are not a substitute for frequent review of the patient's clinical state. Intramuscular naloxone is an alternative in the event that IV access is not possible.

As the duration of action of naloxone is relatively short, the patient must be carefully monitored until spontaneous respiration is reliably re-established. Naloxone is a competitive antagonist and large doses (4 mg) may be required in seriously poisoned patients. For less severe overdosage, administer naloxone 0.2 mg intravenously followed by increments of 0.1 mg every 2 minutes if required.

Naloxone should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to dihydrocodeine overdosage. Naloxone should be administered cautiously to persons who are known, or suspected, to be physically dependent on dihydrocodeine. In such cases, an abrupt or complete reversal of opioid effects may precipitate pain and an acute withdrawal syndrome.

Consider activated charcoal (50 g for adults, 10-15 g for children), if an adult presents within 1 hour of ingestion of more than 420mg or a child more than 3mg/kg.

Pharmacotherapeutic group: Anilides; ATC code: NO2B E71

Paracetamol has analgesic and antipyretic effects. It is only a weak inhibitor of prostaglandin biosynthesis, although there is some evidence to suggest that it may be more effective against enzymes in the CNS than those in the periphery. This fact may partly account for its ability to reduce fever (a central action) and to induce analgesia. Dihydrocodeine is a centrally acting analgesic which produces its effects by its action at opioid binding sites within the CNS.

Paracetamol is well absorbed from the gastrointestinal tract, peak plasma concentrations occurring 0.5-2 hours after ingestion. It is metabolised in the liver and excreted in the urine mainly as glucuronide and sulphate conjugates - less than 5% is excreted as unmodified paracetamol. The plasma half-life is between 1 and 4 hours. Binding to plasma proteins is minimal as therapeutic concentrations but increases as plasma concentrations increase.

Oral dihydrocodeine undergoes considerable presystemic metabolism, but its subsequent metabolism is uncertain. The pharmacokinetics of dihydrocodeine may be similar to those of codeine.

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

Pregelatinised starch

Maize starch

Povidone

Potassium sorbate

Purified talc

Stearic acid

Magnesium stearate

Microcrystalline cellulose

Not applicable

2 years in polypropylene bottles.

3 years in PVC blisters.

No special precautions for storage.

White polypropylene bottles with a cotton wool plug and a white wadless polypropylene screw cap.

Pack size: 100, 500 tablets.

PVC blister strips contained in cardboard cartons.

Pack size: 30, 60, 100 tablets.

Not all pack sizes may be marketed.

No special requirements

Winthrop Pharmaceuticals UK Limited

One Onslow Street

Guildford

Surrey

GU1 4YS, UK

Trading as Winthrop Pharmaceuticals,PO Box 611, Guildford, Surrey, GU1 4YS, UK

PL 17780/0070

1 October 2001/16 March 2009

16 March 2009