PARACODOL TABLETS - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Paracodol tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each soluble tablet contains:

Paracetamol DC 520.0 mg

(equivalent to paracetamol 500.0 mg)

Codeine Phosphate Hemihydrate 8.0 mg

For a full list of excipients see section 6.1

3 PHARMACEUTICAL FORM

Soluble Tablet

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Paracodol Tablets (which contain codeine) are indicated in patients older than 12 years of age for the short term treatment of acute moderate pain (such as muscular and rheumatic pains, headache, migraine, neuralgia, toothache, period pains, aches and pains) which is not considered to be relieved by other analgesics such as paracetamol, ibuprofen or aspirin alone.

4.2 Posology and method of administration

Posology:

Tablets are to be dissolved in water before oral administration.

Adults:

1 – 2 tablets, which may be repeated every four to six hours with a maximum of 8 tablets in 24 hours.

Elderly:

No current evidence for the alteration of the adult dose except where there is impaired hepatic function when dosage reduction may be necessary.

Children aged 12 – 18 years:

1 tablet, which may be repeated every four to six hours with a maximum of 4 tablets in 24 hours.

Children under 12 years:

Paracodol Tablets (which contains Codeine) should not be used in children under 12 years because of the risk of opioid toxicity due to the variable and unpredictable metabolism of codeine to morphine (see sections 4.3 and 4.4).

The duration of treatment should be limited to 3 days and if no effective pain relief is achieved the patients/carers should be advised to seek the views of a physician.

4.3 Contraindications

Hypersensitivity to paracetamol and/or other constituents.

In women during breastfeeding (see section 4.6)

In patients for whom it is known they are CYP2D6 ultra-rapid metabolisers.

In all paediatric patients (0–18 years of age) who undergo tonsillectomy and/or adenoidectomy for obstructive sleep apnoea syndrome due to an increased risk of developing serious and life-threatening adverse reactions (see section 4.4)

4.4 Special warnings and precautions for use

This medicinal product contains 383 mg sodium per tablet, equivalent to 19.15% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

In cases of renal insufficiency, the rate of excretion of codeine metabolites may be reduced, and dosage schedules may need to be revised accordingly. Patients with kidney problems should consult their doctor before taking Paracodol Tablets. Care is advised in the administration of paracetamol with severe renal or hepatic impairment. The hazards of overdose are greater in those with non- cirrhotic alcoholic liver disease.

Do not exceed the stated dose.

Keep out of the reach and sight of children.

If symptoms persist for more than 3 days a doctor should be consulted.

Contains paracetamol. Do not take with other paracetamol-containing products. 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.

CYP2D6 metabolism

Codeine is metabolised by the liver enzyme CYP2D6 into morphine, its active metabolite. If a patient has a deficiency or is completely lacking this enzyme an adequate analgesic effect will not be obtained. Estimates indicate that up to 7% of the Caucasian population may have this deficiency.

However, if the patient is an extensive or ultra-rapid metaboliser there is an increased risk of developing side effects of opioid toxicity even at commonly prescribed doses. These patients convert codeine into morphine rapidly resulting in higher than expected serum morphine levels.

General symptoms of opioid toxicity include confusion, somnolence, shallow breathing, small pupils, nausea, vomiting, constipation and lack of appetite. In severe cases this may include symptoms of circulatory and respiratory depression, which may be life-threatening and very rarely fatal.

Estimates of prevalence of ultra-rapid metabolisers in different populations are summarized below:

Post-operative use in children

There have been reports in the published literature that codeine given post-operatively in children after tonsillectomy and/or adenoidectomy for obstructive sleep apnoea, led to rare, but life-threatening adverse events including death (see also section 4.3). All children received doses of codeine that were within the appropriate dose range; however there was evidence that these children were either ultra-rapid or extensive metabolisers in their ability to metabolise codeine to morphine.

Children with compromised respiratory function

Codeine is not recommended for use in children in whom respiratory function might be compromised including neuromuscular disorders, severe cardiac or respiratory conditions, upper respiratory or lung infections, multiple trauma or extensive surgical procedures. These factors may worsen symptoms of morphine toxicity.

The label will state:

Can cause addiction

For three days use only

Back of Pack

This medicine can only be used for the short term treatment of acute moderate pain when other pain killers have not worked. If you have already taken another pain killer wait at least four hours before taking this medicine. For relief from muscular and rheumatic pains, headache, migraine, neuralgia, toothache, period pains, aches and pains.

If you need to take this medicine continuously 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

Headlines section (to be prominently displayed)

This medicine can only be used for the short term treatment of acute moderate pain which is not relieved by paracetamol, ibuprofen or aspirin alone.

You should only take this product for a maximum of three days at a time. If you need to take it for longer than three days you should see your doctor or pharmacist for advice

This medicine contains codeine 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 this medicine for headaches for more than three days it can make them worse

Section 1: What are Paracodol Tablets for

This medicine can only be used for the short term treatment of acute moderate pain which is not relieved by paracetamol, ibuprofen or aspirin alone. This includes and rheumatic pains, headache, migraine, neuralgia, toothache, period pains, aches and pains.

Section 2: Before you take Paracodol Tablets

This medicine contains codeine 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

Consult your doctor before taking the tablets if you are pregnant or think you may be pregnant.

Do not take codeine while you are breast-feeding. Codeine and morphine passes into breast milk.

Section 3: How should I take Paracodol Tablets?

This medicine should not be taken for more than 3 days. If the pain does not improve after 3 days, talk to your doctor for advice.

This medicine contains codeine 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: Do Paracodol Tablets cause any side effects

Some people may have side-effects when taking this medicine.

Reporting of side-effects

If you get any side-effects, talk to your doctor, pharmacist or nurse. This includes any possible side-effects not listed in this leaflet. You can also report side-effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

By reporting side-effects you can help provide more information on the safety of this medicine.

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

4.5 Interaction with other medicinal products and other forms of interaction Paracetamol should be given with care to patients taking other drugs, which affect the liver.

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 Fertility, pregnancy and lactation

Pregnancy

There is inadequate evidence of safety of the drug in human pregnancy, but it has been in wide use for many years without apparent ill-consequence, although there is evidence that exposure to codeine during pregnancy may give a higher incidence of respiratory malformations. If drug therapy is needed in pregnancy this drug can be used if there is no safer alternative. At normal doses, low levels of paracetamol and codeine are present in breast milk.

Epidemiological studies in human pregnancy have shown no ill effects dues to paracetamol used in the recommended dosage. Epidemiological studies on neurodevelopment in children exposed to paracetamol in utero show inconclusive results. If clinically needed, patients should follow the advice of their doctor regarding its use.

Lactation

Paracetamol is excreted in the breast milk but not in a clinically significant amount.

Codeine should not be used during breastfeeding (see section 4.3). At normal therapeutic doses codeine and its active metabolite 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 metabolite, morphine, may be present in breast milk and on very rare occasions may result in symptoms of opioid toxicity in the infant, which may be fatal.

4.7 Effects on ability to drive and use machines

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 taking 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:

o The medicine has been taken to treat a medical or dental problem and

o You have taken it according to the information provided with the medicine and

o It was not affecting your ability to drive safely

4.8 Undesirable effects

Adverse effects of paracetamol are rare but hypersensitivity including skin rash may occur. Very rare cases of serious skin reactions have been reported.

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

Codeine may sometimes cause constipation.

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

Prolonged use of a painkiller for headaches can make them worse.

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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

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

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.

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.

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).

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 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.

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.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Other Analgesics and Antipyretics, ATC code: N02B.

Paracodol has analgesic and antipyretic actions.

Codeine is a centrally acting weak analgesic. Codeine exerts its effect through u opioid receptors, although codeine has low affinity for these receptors, and its analgesic effect is due to its conversion to morphine. Codeine, particularly in combination with other analgesics such as paracetamol, has been shown to be effective in acute nociceptive pain.

5.2 Pharmacokinetic properties

Not applicable.

5.3 Preclinical safety data

Paracetamol

Conventional studies using the currently accepted standards for the evaluation of toxicity to reproduction and development are not available.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Povidone

Sodium hydrogen carbonate

Anhydrous sodium carbonate

Anhydrous citric acid

Mannitol

Saccharin sodium

Sodium docusate

Sodium benzoate

6.2 Incompatibilities

None known.

6.3 Shelf life

36 months.

6.4 Special precautions for storage

Store in the original package in order to protect from moisture.

6.5 Nature and contents of container

Aluminium foil/ polyethylene laminate strip pack.

Pack sizes: 2,10, 12, 16, 24, 30, 32.

6.6 Special precautions for disposal

None.

7 MARKETING AUTHORISATION HOLDER

Bayer plc

400 South Oak Way

Reading

RG2 6AD