Co-Codamol 8mg/500mg Tablets

Paracetamol and Codeine Tablets

For excipients, see section 6.1.

Tablets

White tablets, broken breakline on one face. Debossed <AB> on other side.

For the short term treatment of acute moderate pain which is not relieved by paracetamol, ibuprofen or aspirin alone.'

For the symptomatic relief of pain including, headache, migraine, toothache, period pains, rheumatic pains, including muscle pains and backache.

For oral use.

Adults and children over 12 years: one or two tablets to be swallowed with water. The dose should not be repeated more frequently than every four to six hours and not more than four times in any 24 hour period. Maximum dose is 8 tablets (4.0gm of paracetamol and 64mg of codeine in divided doses) per 24 hours.

Elderly

The dosage should be reduced.

Hepatic impairment

The dosage should be reduced. Use in liver disease is contraindicated (see 4.3 Contraindications).

Renal impairment

The dosage should be reduced in moderate to severe renal impairment (see also 4.8 Undesirable Effects).

For concomitant illnesses/conditions where dose reduction may be appropriate, see 4.4 Special Warnings and Precautions for Use.

Do not take for more than 3 days continuously without medical review.

i. Paracetamol:

Hypersensitivity to paracetamol and/or other constituents.

ii. Codeine:

Acute respiratory depression

Hypersensitivity to codeine or other opioid analgesics.

Liver disease.

Acute alcoholism.

Use should be avoided in patients with raised intracranial pressure or head injury (in addition to the risk of respiratory depression and increased intracranial pressure, may affect pupillary and other responses vital for neurological assessment).

Codeine is also contraindicated in conditions where inhibition of peristalsis is to be avoided, where there is a risk of paralytic ileus, where abdominal distension develops, or in acute diarrhoeal conditions such as acute ulcerative colitis or antibiotic associated colitis.

Not to be used in children of 12 years and under.

i. Paracetamol:

Care is advised in the administration of paracetamol to patients with renal or hepatic impairment. The hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease. Paracetamol should be given with care to patients with alcoholic dependence.

Paracetamol is well tolerated by the majority of people with asthma. However, a small percentage of aspirin sensitive asthmatics are also sensitive to paracetamol. The likelihood of a reaction to paracetamol increases with a patient's level of sensitivity to aspirin (see also 4.8 Undesirable Effects).

Do not exceed the recommended dose.

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

Leaflet:

Immediate medical advice should be sought in the event of an overdose, even if you feel well, because of the risk of delayed, serious liver damage.

Label:

1. Immediate medical advice should be sought in the event of an overdose, even if you feel well.

2. Do not take with any other paracetamol-containing products.

ii. Codeine:

Use with caution in asthma, and decreased respiratory reserve. Avoid use during an acute attack (see 4.3 Contraindications). It should only be used with caution or in reduced dose in debilitated patients, hypotension, hypothyroidism, urethral stricture, adrenocortical insufficiency, prostatic hypertrophy, shock, convulsive disorders, renal impairment or hepatic impairment (see 4.2 posology).

It should be used with caution in those with a history of drug abuse.

Discontinuation should be carried out gradually in patients who may have developed physical dependence, to avoid precipitating withdrawal symptoms.

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 label will state:

Front of Pack

• Can cause addiction

• For three days use only

Back of Pack

List of indication as agreed in 4.1 of the SmPC

If you need to use this medicine for more than three days you should see your doctor or pharmacist.

This medicine contains codeine which can cause addiction if you take it continuously for more than three days. If you take this medicine for headaches for more than three days it can make them worse.

Leaflet:

Section 1: What the medicine is for

Succinct description of the indications from 4.1 of the SmPC

Section 2: Before taking

• This medicine contains codeine [or dihydrocodeine] which can cause addiction if you take it continuously for more than three days. This can give you withdrawal symptoms from the medicine when you stop taking it

• If you take a painkiller for headaches for more than three days it can make them worse

• Pregnancy and breast-feeding:

Usually it is safe to take Co-codamol 8mg/500mg Tablets while breast feeding as the levels of codeine phosphate 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.

Section 3: Dosage

• Do not take for more than 3 days. If you need to use this medicine for more than three days you must speak to your doctor or pharmacist

• This medicine contains codeine [or dihydrocodeine] and can cause addiction if you take it continuously for more than three days. When you stop taking it you may get withdrawal symptoms. You should talk to your doctor or pharmacist if you think you are suffering from withdrawal symptoms

Section 4: Side effects

• Some people may have side-effects when taking this medicine. If you have any unwanted side-effects you should seek advice from your doctor, pharmacist or other healthcare professional. Also you can help to make sure that medicines remain as safe as possible by reporting any unwanted side-effects via the internet at www.yellowcard.gov.uk; alternatively you can call Free phone 0808 100 3352 (available between 10am-2pm Monday – Friday) or fill in a paper form available from your local pharmacy.

How do I know if I am addicted?

• If you take the medicine according to the instructions on the pack it is unlikely that you will become addicted to the medicine. However, if the following apply to you it is important that you talk to your doctor:

• You need to take the medicine for longer periods of time

• You need to take more than the recommended dose

• When you stop taking the medicine you feel very unwell but you feel better if you start taking the medicine again

Prolonged use of any type of painkiller for headaches can make them worse. If this situation is experienced or suspected, medical advice should be obtained and treatment should be discontinued. The diagnosis of medication overuse headache (MOH) should be suspected in patients who have frequent or daily headaches despite (or because of) the regular use of headache medications.

Co-codamol 8mg/500mg Tablets contain parahydroxybenzoates (E218, E214 and E216), which may cause allergic reactions (possibly delayed).

i. Paracetamol:

Alcohol: Paracetamol should be given with care to patients with alcohol dependence (see Section 4.4).

Analgesics: Diflunisal increases blood concentrations of paracetamol.

Anion-exchange resins: Absorption reduced by cholestyramine; administration should be separated by at least 1 hour.

Antibacterials: Isoniazid may increase the risk of hepatotoxicity with therapeutic doses of paracetamol.

Anticoagulants: 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.

Antiepileptics: Carbamazepine, phenobarbital, phenytoin and primidone can reduce the effects of paracetamol and increase the risk of hepatotoxicity.

Motility stimulants: The speed of absorption of paracetamol may be increased by metoclopramide or domperidone.

Oral Contraceptives: Paracetamol is cleared from the body more quickly in women taking oral contraceptives and the analgesic effects may be reduced.

Uricosurics: Probenecid can reduce the loss of paracetamol from the body.

ii. Codeine:

Alcohol: the effects of alcohol may be enhanced.

Anti-arrhythmics: codeine delays the absorption of mexiletine. The analgesic activity of codeine is likely to be significantly impaired by quinidine in extensive metabolisers of codeine.

Antidepressants: Severe CNS excitation or depression (including hypertension or hypotension) has been reported with the concurrent use of monoamine oxidase inhibitors ( MAOIs) and pethidine. It is therefore possible that a similar interaction may occur with other opioid analgesics. The depressant effects of opioid analgesics may be enhanced by tricyclic antidepressants.

Antipsychotics: enhanced sedative and hypotensive effect.

Anxiolytics and hypnotics: enhanced sedative effect.

Domperidone and metoclopramide: codeine antagonises the effect of metoclopramide and domperidone on gastrointestinal activity.

Antidiarrhoeal and antiperistaltic agents: Concurrent use of codeine with agents such as loperamide and kaolin may increase the risk of severe constipation.

Ulcer-healing drugs: cimetidine inhibits the metabolism of opioid analgesics resulting in increased plasma concentrations.

Interference with laboratory tests

Opioid analgesics interfere with a number of laboratory tests including plasma amylase, lipase, bilirubin, alkaline phosphatase, lactate dehydrogenase, alanine aminotransferase and aspartate aminotransferase. Opioids may also interfere with gastric emptying studies as they delay gastric emptying and with hepatobiliary imaging using technetium Tc 99m disofenin as opioid treatment may cause constriction of the sphincter of Oddi and increase biliary tract pressure.

i. Paracetamol:

Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol use in the recommended dosage, but patients should follow the advice of their doctor regarding its use.

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

ii. Codeine:

As with all medications caution should be exercised during pregnancy, especially in the first trimester. A possible association with respiratory and cardiac malformations has been reported. Regular use of codeine during pregnancy may cause physical dependence in the foetus leading to withdrawal symptoms in the neonate. Administration of codeine during labour may depress respiration in the neonate. Opioid analgesics may cause gastric stasis during labour, increasing the risk of inhalation pneumonia in the mother.

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.

i. Paracetamol:

None.

ii. Codeine:

Codeine produces sedationand may cause blurred or double vision. If affected patients should be advised not to drive or operate machines.

i. Paracetamol:

Adverse effects of paracetamol are rare.

Haematological: There have been reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol.

Immune system: Hypersensitivity including skin rash may occur. A small percentage of aspirin-sensitive asthmatics are also sensitive to paracetamol. In such cases, the deterioration in respiratory function induced by paracetamol is milder and shorter than with aspirin (see also 4.4 Special Warnings and Precautions for Use).

Renal and urinary disorders: Nephropathy has been associated with chronic high dose use.

ii. Codeine:

The most common side effects include constipation, drowsiness, nausea and vomiting (particularly in the initial stages).

Other less frequent and rare side-effects include the following:

Skin: rashes, urticaria and pruritus, sweating, flushing and facial oedema.

Gastrointestinal: dry mouth, biliary spasm, convulsions and anorexia.

Ophthalmic: blurred or double vision or other changes in vision.

Central Nervous System: confusion (with large doses), dizziness, headache (prolonged use of a painkiller for headaches can make them worse), vertigo, mood changes (including depression and more rarely euphoria), muscle rigidity, uncontrolled muscle movements, hallucinations and nightmares.

Cardiovascular: hypotension (with large doses), tachycardia, bradycardia and palpitations.

Respiratory: respiratory depression and dyspnoea.

Urinary: difficulty with micturition, increased frequency and/or decreased amount of micturition, dysuria, ureteric spasm.

Sexual dysfunction: erectile dysfunction.

Tolerance may develop.

Regular prolonged use of codeine is known to lead to addiction and symptoms of restlessness and irritability may result when treatment is then stopped.

i. 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

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.

Treatment

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

ii. Codeine:

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 triad of coma, pinpoint pupils and respiratory depression is considered indicative of opioid overdosage with dilation of the pupils occurring as hypoxia develops.

Nausea and vomiting are common Other opioid overdose symptoms include hypothermia, confusion, convulsions, severe dizziness, severe drowsiness, hypotension and tachycardia (possible but unlikely), nervousness or restlessness, excitement, hallucinations, bradycardia, circulatory failure, slow or troubled breathing, severe weakness, convulsions, especially in infants and children. Rhabdomyolysis, progressing to renal failure, has been reported in overdosage with opioids.

The effects in overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs.

Treatment

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 350mg or a child more than 5mg/kg. In acute overdosage with respiratory depression or coma, the specific opioid antagonist naloxone is indicated using one of the recommended dose regimens– repeated doses may be required in a seriously poisoned patient as naloxone is a competitive antagonist with a short half life. Patients should be observed closely for at least four hours after ingestion, or eight hours if a sustained release preparation has been taken.

Paracetamol has analgesic and antipyretic actions.

ii. Codeine:

Codeine has similar uses to morphine but is much less potent as an analgesic.

i. Paracetamol:

Paracetamol is readily absorbed from the gastro-intestinal tract with peak plasma concentrations occurring 30 minutes to two 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 hour to four hours. At usual therapeutic concentrations plasma protein binding is negligible.

ii. Codeine:

Codeine is well absorbed from the gastrointestinal tract following oral administration. It is metabolised in the liver to morphine, and norcodeine which are both excreted in the urine partly as conjugates with glucuronic acid. Most of the excretion products appear in the urine within 6 hours and up to 86% of the dose is excreted in 24 hours. About 70% of the dose is excreted as free codeine, 10% as free and conjugated morphine and a further 10% as free or conjugated norcodeine. Only traces are found in the faeces. The plasma half life is between approximately three and four hours.

Paracetamol& codeine:

There is no pre-clinical data of relevance to the prescriber which is additional to that already included in the other sections of the SmPC.

Potato starch

Maize starch

Talc

Povidone

Stearic acid

Magnesium stearate

Nipasept *

* Nipasept consists of methyl-p-hydroxybenzoate (E218), ethyl-p-hydroxy benzoate (E214) and propyl-p-hydroxybenzoate (E216).

None.

Do not store above 25^oC

Blisters: Store in the original package

Blister packs:

8, 10, 12, 16, 20, 24, 28, 30, 32 as Pharmacy packs

Blister strips consist of a 35gsm paper/9µ soft tempered aluminium foil lid and 250µ PVC film base in cartons.

Or

Blister strips consist of a 250µ hard aluminium foil laminated to 15 µ rigid PVC film and 250µ PVC film base in cartons.

No special requirements.

Bristol Laboratories Ltd,

Unit 3, Canalside,

Northbridge Road

Berkhamsted

HP4 1EG

UK

PL 17907/0162

25/07/2006

27/07/2011