SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Paracodol Capsules

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Paracetamol    500.0 mg

Codeine Phosphate 8.0 mg

3    PHARMACEUTICAL FORM

Capsules

4 CLINICAL PARTICULARS

4.1    Therapeutic indications

Paracodol Capsules (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

For oral administration.

Adults

1 - 2 capsules. If necessary, the dose may be repeated every 4 - 6 hours with a maximum of 8 capsules in 24 hours.

Elderly

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

Children aged 12 - 18 years

1 capsule. If necessary, the dose may be repeated every 4 - 6 hours with a maximum of 4 capsules in 24 hours.

Children under 12 years

Paracodol Capsules (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 physician.

4.3 Contraindications

•    Hypersensitivity to paracetamol and/or other constituents of Paracodol capsules.

•    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

Keep out of the reach of children.

Warning: Do not exceed the stated dose.

If symptoms persist, consult you doctor.

An overdose of paracetamol can cause hepatic necrosis. Preparations containing paracetamol should be given with care to patients with impaired renal and liver function. The hazards of overdose are greater in those with alcoholic liver disease.

Do not take with any 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:

Population	Prevalence %
African/Ethi opi an	29%
African American	3.4% to 6.5%
Asian	1.2% to 2%
Caucasian	3.6% to 6.5%
Greek	6.0%
Hungarian	1.9%
Northern European	1% - 2%

Post-operative use in children

There have been reports in the published literature that codeine given postoperatively 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:

Front of Pack

•    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 pain, 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

The leaflet will state:

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 Capsules 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 muscular and rheumatic pains, headache, migraine, neuralgia, toothache, period pain, aches and pains.

Section 2: Before you take Paracodol Capsules

•    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 capsules 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 Capsules?

•    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 Capsules cause any 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.mhra.gov.uk/yellowcard alternatively you can call Freephone 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

4.5 Interaction with other medicinal products and other forms of interaction

Paracetamol should be given with care to patients taking other drugs that affect the liver.

The speed of absorption of paracetamol may be increased by metoclopramide or domperidone. Concurrent use need not be avoided.

The absorption of paracetamol may possibly be reduced if cholestyramine is given at the same time, but the reduction in absorption is small if given an hour later.

The anticoagulatory effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding.

4.6 Fertility, pregnancy and lactation

Pregnancy

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.

There is inadequate evidence of safety of codeine in pregnancy. Codeine has been used for many years without apparent ill-consequences, and animal studies have not shown any hazard.

The use of Paracodol Capsules in pregnancy is therefore acceptable if there is no safer alternative.

Lactation

Paracetamol is excreted in 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 reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these 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 of suspected adverse reactions

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.

4.9 Overdose

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 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.

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.

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 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.

Paracetamol is well known for its analgesic and antipyretic actions. Codeine is a centrally acting weak analgesic. Codeine exerts its effect through p 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

Codeine phosphate is well absorbed after oral administration, producing peak plasma concentrations in about one hour. The plasma half-life is between 3 and 4 hours, excretion being mainly in the urine.

Paracetamol is also readily absorbed after oral administration, with peak plasma concentrations occurring between 30 minutes and 2 hours after ingestion.

The plasma half life varies between 1 and 4 hours. Excretion is mainly via the urine.

5.3 Preclinical safety data

None

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Capsules contents Pregelatinised Maize Starch Colloidal Silicon Dioxide Magnesium Stearate (E 572)

Capsule shell

Titanium Dioxide (E 171)

Gelatin

Printing ink Shellac (E 904)

Red Iron Oxide (E 172) Propylene Glycol

6.2 Incompatibilities

None stated.

Shelf life

36 months.

6.4 Special precautions for storage

Do not store above 25 C

6.5 Nature and contents of container

Blisters of white 250 micron PVC/40 gsm PVDC base with 30 micron hard temper aluminium foil lidding.

Pack sizes: 2, 10, 20, 24, 30, 32.

6.6 Special precautions for disposal

None.

7    MARKETING AUTHORISATION HOLDER

Bayer plc Bayer House Strawberry Hill Newbury,

Berkshire.

RG14 1JA.

Trading as Bayer plc, Consumer Care Division

MARKETING AUTHORISATION NUMBER(S)

PL 00010/0339

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

30/06/1994

10    DATE OF REVISION OF THE TEXT

14/11/2016