Boots Paracetamol and Codeine Extra Capsules

1. Name Of The Medicinal Product

Boots Paracetamol and Codeine Extra Capsules

2. Qualitative And Quantitative Composition

Active ingredients	mg/capsule
Paracetamol	500.0
Codeine phosphate hemihydrate	8.0
Caffeine	30.0

3. Pharmaceutical Form

Capsules, hard.

4. Clinical Particulars

4.1 Therapeutic Indications

For the fast relief of pain. For the short term treatment of acute moderate pain which is not relieved by paracetamol, ibuprofen or aspirin alone such as: headache, migraine, period pain, dental pain, neuralgia and rheumatic pain (including muscular pain and backache).

4.2 Posology And Method Of Administration

Adults and children over 12 years

Two capsules to be taken up to four times a day, doses being repeated not more than every four hours, up to a maximum of eight capsules in 24 hours.

Children under 12 years

Not recommended.

Elderly

There is no need for dosage reduction in the elderly.

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

4.3 Contraindications

Hypersensitivity to any of the ingredients. Severe liver disease.

4.4 Special Warnings And Precautions For Use

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.

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.

Contains Ponceau 4R (E124) which may cause allergic reactions.

Do not exceed the stated dose.

If symptoms persist consult your doctor.

Do not give to children under 12.

Contains paracetamol.

Do not take with any other paracetamol-containing products.

Keep all medicines out of the reach of children.

The label will state:

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

Front of pack

• Can cause addiction

• For three days use only

Back of pack

• List of indications as agreed in 4.1 of the SPC

• If you need to take this medicine continuously for more than 3 days you should see your doctor or pharmacist

• This medicine contains codeine which can cause addiction if you take it continuously for more than 3 days. If you take this medicine for headaches for more than 3 days it can make them worse.

The leaflet (or combined label/leaflet) will state:

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.

'Headlines' section (to be prominently displayed)

• This medicine can only be used for.....(indications)

• You should only take this product for a maximum of 3 days at a time. If you need to take it for longer than 3 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 3 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 3 days it can make them worse.

“What this medicine is for” section

• Succinct description of the indications from 4.1 of the SPC

“Before you take this medicine” section

• This medicine contains codeine which can cause addiction if you take it continuously for more than 3 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 3 days it can make them worse.

Usually it is safe to take this medicine while breastfeeding as the levels of the active ingredients of this medicine 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.

“How to take this medicine” section

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

• This medicine contains codeine and can cause addiction if you take it continuously for more than 3 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.

“Possible side effects” section

• 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 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?” section

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 you doctor:

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

• You need to take more than the recommended amount

• 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

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.

Codeine should be given with care to patients receiving monoamine oxidase inhibitors. The depressant effects of codeine are enhanced by depressants of the central nervous system including alcohol; these interactions are unlikely to be significant at the dosage involved.

4.6 Pregnancy And Lactation

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. However in view of the possible association of codeine with respiratory depression and heart malformations, use of the product during this period should be avoided.

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.

Paracetamol and caffeine pass into breast milk in very small amounts which are probably insignificant and considered to be compatible with breast feeding.

4.7 Effects On Ability To Drive And Use Machines

No adverse effects known.

4.8 Undesirable Effects

Adverse effects of paracetamol are rare but hypersensitivity including skin rash may occur. There have been very rare reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol. Other side effects may include constipation, nausea, dizziness and drowsiness.

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

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

4.9 Overdose

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.

• Regularly consumes ethanol in excess of recommended amounts.

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 include 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) 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.

Codeine

Symptoms

Central nervous system depression may develop as well as respiratory depression. The pupils may be pin-point in size and nausea and vomiting are common. Possible but unlikely effects are hypotension and tachycardia. The effects in overdosage of codeine are potentiated by simultaneous ingestion of alcohol and psychotropic drugs.

Management

If coma or respiratory depression is present give naloxone, preferably intravenously, at a dose of 0.4 to 2mg for adults and 0.01mg/kg body weight for children. Repeat the dose if there is no response within two minutes. Large doses (4mg) of naloxone may be required in a seriously poisoned patient. Intramuscular naloxone is an alternative in the event that IV access is not possible, or if the patient is threatening to self-discharge when it may help reduce the risk of respiratory arrest. Failure of a definite opioid overdose to respond to large doses of naloxone suggests that another CNS depressant drug or brain damage is present.

Observe the patient carefully for recurrence of CNS and respiratory depression. Repeated doses of naloxone may be required. If so, intravenous infusion of naloxone may be useful. An infusion of 60% of the initial dose per hour is a useful starting point. A 200 microgram/ml solution for infusion using an IV pump can be used and the dose adjusted to clinical response. Infusions are not a substitute for frequent review of the patient's clinical state.

A clear airway, adequate ventilation and oxygenation should be established without delay if consciousness is impaired.

Consider activated charcoal (50g for adults; 10-15g for children) if an adult presents within 1 hour of ingestion of more than 350mg, or a child more than 5mg/kg, provided the airway can be protected.

Observe patient for at least 4 hours after ingestion. Other supportive measures should be taken as indicated by the patient's progress.

Caffeine

Symptoms

CNS stimulation: Anxiety, nervousness, restlessness, insomnia, excitement, muscle twitching, confusion.

Cardiac: Tachycardia, cardiac arrythmia.

Gastric: Abdominal or stomach pains.

Other: Diuresis, facial flushing.

The symptoms of caffeine overdose may be masked by the depression of consciousness associated with possible codeine overdose when associated with this combination.

Treatment

Treatment is primarily symptomatic and supportive. Acute toxicity is unlikely to occur with the low levels of caffeine in this product.

CNS symptoms can be treated with intravenous diazepam, phenobarbitone or phenytoin.

For cardiac symptoms monitoring of ECG is required.

Diuresis should be treated by maintaining fluid and electrolyte balance.

Gastric symptoms can be treated using antacids.

If acute poisoning is suspected treatment generally includes emesis with ipecacuanha syrup and/or gastric lavage if caffeine has been ingested within 4 hours in amounts over 15mg/kg bodyweight. However whilst treatment of this nature would be beneficial in reducing absorption of caffeine, consideration would need to be given to the level on consciousness of the patient in view of the sedating effect of codeine in this product combination.

Administration of activated charcoal may be useful within the first 4 hours if precautions are taken to minimize aspiration. Magnesium sulphate cathartic may also be helpful.

To enhance elimination haemoperfusion is usually more effective than dialysis.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Paracetamol is an analgesic with antipyretic activity.

Codeine phosphate is an opioid analgesic which acts via the central nervous system.

Caffeine is a central nervous system stimulant and contributes to the feeling of well being. Caffeine has also been shown to act as an analgesic adjuvant when used in combination with peripherally acting analgesics such as paracetamol

5.2 Pharmacokinetic Properties

Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 30 minutes to 2 hours after ingestion. Paracetamol is metabolised in the liver and excreted in the urine mainly as the glucuronide and sulphate conjugates, with about 10% as glutathione conjugates. Less than 5% is excreted as unchanged paracetamol. The elimination half life varies from about 1 to 4 hours. Plasma protein binding is negligible at usual therapeutic concentrations, although this is dose dependent.

Codeine phosphate is absorbed from the gastrointestinal tract and peak plasma concentrations occur after about one hour. Codeine is metabolised by O- and N-demethylation in the liver to morphine and norcodeine. Codeine and its metabolites are excreted almost entirely by the kidney, mainly as conjugates with glucuronic acid. The plasma half life has been reported to be between 3 and 4 hours.

Caffeine is absorbed readily after oral administration and is widely distributed throughout the body. Caffeine passes readily into the CNS and into saliva. In adults, caffeine is metabolised almost completely via oxidation, demethylation and acetylation and is excreted in the urine as various metabolites with only about 1% being excreted unchanged. Elimination half life is approximately 3 to 6 hours in adults.

5.3 Preclinical Safety Data

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

6. Pharmaceutical Particulars

6.1 List Of Excipients

Sodium lauryl sulphate

Magnesium stearate

Sodium starch glycolate (type A)

Capsule shell

Gelatin

Yellow iron oxide (E172)

Titanium dioxide (E171)

Quinoline yellow (E104)

Ponceau 4R (E124)

Printing ink

Black iron oxide (E172)

Shellac

Propylene glycol

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

24 months.

6.4 Special Precautions For Storage

Do not store above 30ºC. Store in the original package.

6.5 Nature And Contents Of Container

A child-resistant push through pack of opaque 250 micron PVC/40gsm PVdC blisters, heat sealed to 35gsm Glassine paper/9 micron soft temper aluminium foil.

Pack sizes: 6, 8, 12, 16, 18, 24, 32

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

The Boots Company PLC

1 Thane Road West

Nottingham NG2 3AA

8. Marketing Authorisation Number(S)

PL 0014/0613

9. Date Of First Authorisation/Renewal Of The Authorisation

2 February 2001

10. Date Of Revision Of The Text

November 2010