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Co-Dydramol Tablets

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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Co-dydramol Tablets BP

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Paracetamol BP 500mg and Dihydrocodeine Tartrate BP 10mg For excipients see section 6.1

3.    PHARMACEUTICAL FORM

Tablets

4.    CLINICAL PARTICULARS

4.1    Therapeutic indications

Co-dydramol is indicated for the treatment of moderate pain.

4.2    Posology and method of administration

Adults and children over 12 years

One tablet every four hours. This may be increased to two tablets four times a day, if necessary.

Children

Co-dydramol is not recommended for children under 12 years.

Elderly

Dosage should be reduced in the elderly.

Route of administration

Oral

4.3 Contraindications

Respiratory depression, obstructive airways disease, liver disease, hypersensitivity to dihydrocodeine or paracetamol and/or other constituents.

4.4 Special warnings and precautions for use

Co-dydramol should be given with caution in patients with allergic disorders and should not be given during an attack of asthma. Caution should also be observed if there is marked impairment of liver function or advanced kidney disease.

Dosage should be reduced in the elderly, in hypothyroidism, in chronic hepatic disease and in renal insufficiency. Alcohol should be avoided whilst under treatment with Co-dydramol. An overdosage can cause hepatic necrosis.

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 non-cirrhotic alcoholic liver disease.

Do not exceed the recommended dose.

If symptoms persist consult your doctor.

Keep out of the reach of children.

Patients should be advised not to take other paracetamol containing products concurrently.

In the event of an overdose immediate medial advice should be sought because of the delayed risk of 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 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.

4.5 Interaction with other medicinal products and other forms of interaction

Additive CNS depression may occur with alcohol; should therefore be avoided.

Dihydrocodeine: The absorption of mexiletine may be delayed. The effects of hypnotics and anxiolytics are potentiated. Dihydrocodeine may excite or depress the central nervous system if administered with MAOI’s. The effects of metoclopramide and domperidone are antagonised. There may be enhanced sedative and hypotensive effects when given concurrently with antipsychotics.

Paracetamol: 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 use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.

4.6 Pregnancy and lactation

There is no, or inadequate, evidence of safety in human pregnancy but dihydrocodeine and paracetamol have been used for many years without apparent ill consequence. It is advised that Co-dydramol be avoided in the latter stages of pregnancy due to the risk of respiratory depression in the neonate. Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol used in the recommended dosage, but patients should follow the advice of their doctor regarding its use. Lactation: Codeine is excreted in breast milk but in amounts too small to be harmful. Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breast feeding.

4.7 Effects on ability to drive and use machines

Nausea, headache, vertigo and giddiness may occur in a few patients.

If affected, do 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 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

Constipation, nausea, vomiting, headache, vertigo and giddiness may occur and are relatively more common when the dose of dihydrocodeine is increased above 30mg. If constipation occurs, it can be treated with a gentle laxative. Tolerance, psychological and physical dependence may occur with large doses of dihydrocodeine.

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.

Side effects of paracetamol are rare, but hypersensitivity including skin rashes may occur. There have been reports of blood dyscrasias including thrombocytopenia and agranulocytosis, acute pancreatitis, but these were not necessarily causality related to paracetamol.

4.9 Overdose (symptoms, emergency procedure, antidotes)

Conservative management is recommended; gastric lavage should be carried out within two hours of ingestion, Severe respiratory depression can be treated with naloxone hydrochloride 0.4 to 2mg subcutaneously, repeated as required at two or three minute intervals.

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

a)    is on long term treatment with carbamazepine, phenobarbitone, 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 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 concentration are unreliable) but results should not delay initiation of treatment beyond 8 hours after ingestion, as 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.

5.    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Co-dydramol (dihydrocodeine tartrate and paracetamol in combination 1:50) is used for the treatment of moderate pain.

5.2 Pharmacokinetic properties

The pharmacokinetics of dihydrocodeine may be similar to those of codeine.

Paracetamol is readily absorbed from the gastro-intestinal tract with peak plasma concentrations occurring about 30 minutes to 2 hours after ingestion. It is metabolised in the liver and excreted in the urine mainly as the glucuronide and sulphate conjugates. Less than 5% is excreted as unchanged paracetamol. The elimination half-life varies from about one to four hours.

Plasma-protein binding is negligible at usual therapeutic concentrations but increases with increasing concentrations.

5.3 Preclinical safety data

Not applicable

6.    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Starch BP Povidone BP Pregelatinised Starch BP Nipasept sodium HSE Water BP

Sodium starch glycollate BP Magnesium stearate BP

6.2 Incompatibilities

None known.

6.3 Shelf-life

36 months in polypropylene containers 24 months in blisters

6.4 Special precautions for storage

Store in a cool, dry place. Store in the original package.

6.5 Nature and contents of container

(i) Polypropylene tubular container with an open end equipped to accept a polyethylene closure with a tamper-evident tear strip and is of the

appropriate size to accommodate 20, 24, 28, 30, 32, 40, 50, 100, 250, 500, 1000 or 5000 tablets.

(ii) PVdC coated PVC/Aluminium blisters (60g/m2 PVdC on 250p PVC/20p Al) to accommodate 20, 24, 28, 30, 32, 40, 50 and 100 tablets.

6.6 Instructions for use/handling

No special instructions.

7    MARKETING AUTHORISATION HOLDER

Norton Healthcare Limited

T/A IVAX Pharmaceuticals UK

Ridings Point

Whistler Drive

Castleford

West Yorkshire

WF10 5HX.

8. Marketing Authorization Number

PL 00530/0228

9. Date of First Authorization/Renewal of Authorization

Granted 01.05.86 / Renewed 01.05.91 / 04.10.96

10 DATE OF REVISION OF THE TEXT

14/11/2014