Boots Paracetamol and Codeine Extra Capsules

Summary of Product Characteristics Updated 15-Jul-2019 | THE BOOTS COMPANY PLC

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

This medicine is indicated in patients older than 12 years of age.

For the fast relief of pain. For the short term treatment of acute moderate pain which is not considered to be relieved by other analgesics (e.g. 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

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 aged 16 to 18 years

One or two capsules every 6 hours when necessary up to a maximum of eight capsules in 24 hours

Children aged 12 to 15 years

One capsule every 6 hours when necessary up to a maximum of 4 capsules in 24 hours.

Children under 12 years

Codeine should not be used in children below the age of 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).

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.

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).

In women during breastfeeding (see section 4.6).

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

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.

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

Do not take more than the label tells you to.

If you do not get better, talk to your doctor.

Do not give to children under 12.

Contains paracetamol.

Do not take anything else containing paracetamol while taking this medicine

Keep all medicines out of the reach of children.

The label will state:

Talk to a doctor at once if you take too much of this medicine, 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:

Talk to a doctor at once if you take too much of this medicine, even if you feel well. This is because too much paracetamol can cause 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.

“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

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.go.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

“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

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 summarised below:

Population

Prevalence %

African/Ethiopian

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% to 2%

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.

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 Fertility, pregnancy and lactation

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

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.

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

A large amount of data on pregnant women indicate neither malformative, nor feto/neonatal toxicity. Epidemiological studies on neurodevelopment in children exposed to paracetamol in utero show inconclusive results. If clinically needed, paracetamol can be used during pregnancy however it should be used at the lowest effective dose for the shortest possible time and at the lowest possible frequency.

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 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 a '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

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.

Paracetamol: Very rare cases of serious skin reactions have been reported.

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

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 is a centrally acting weak analgesic. Codeine exerts its effect through µ 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, has been shown to be effective in acute nociceptive pain.

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

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

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 30°C. 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

09 July 2019

Company Contact Details
THE BOOTS COMPANY PLC
Address

1 Thane Road West, Beeston, Nottingham, NG2 3AA

Fax

+44 (0)1159 592 565

Telephone

+44 (0)1159 595 165