Clear Dissolving Pain Relief Plus Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Clear Dissolving Pain Relief Plus Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Active ingredient mg/tablet
Paracetamol pdr EP 250.00
Paracetamol DC FP 272 GSR 260.00*
Codeine Phosphate EP 8.00
Anhydrous Caffeine (ALKD) pdr EP 30.00 *Contains 10mg gelatin
3 PHARMACEUTICAL FORM
Tablet
4.1 Therapeutic indications
For the short term treatment of acute moderate pain which is not relieved by paracetamol, ibuprofen or aspirin alone.
For the relief of headache, migraine, period pain, dental pain, neuralgia, rheumatic and muscular pain and backache.
Codeine is indicated in patients older than 12 years of age for the treatment of acute moderate pain which is not considered to be relieved by other analgesics such as paracetamol or ibuprofen (alone).
For oral administration.
4.2 Posology and method of administration Adults and the Elderly
Use the lowest effective dose for the shortest period of time
One to two tablets, if necessary, three or four times daily at intervals of not
less than four hours, up to a maximum of eight tablets in 24 hours.
These doses should be taken dissolved in half a tumbler of water.
Children aged 12 - 18 years
Use the lowest effective dose for the shortest period of time
One to two tablets, if necessary, three or four times daily at intervals of not
less than four hours, up to a maximum of eight tablets in 24 hours.
These doses should be taken dissolved in half a tumbler of water.
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.
Children aged less than 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).
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.
Do not exceed the stated dose.
If symptoms persist, consult your doctor.
Do not give to children under 12 years Contains Paracetamol.
Do not take with any other paracetamol-containing products.
Keep all medicines out of the reach of children.
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/ 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%-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:
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
• Relieves headache, migraine, period pain, dental pain, neuralgia, rheumatic and muscular pain and backache.
• 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 (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 the relief of headache, migraine, period pain, dental pain, neuralgia, rheumatic and muscular pain and backache.
• 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 the medicine is for
• It can be used to relieve headache, migraine, period pain, neuralgia, toothache, rheumatic and muscular pain and backache.
Section 2: Before taking
• 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
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 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 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
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 may delay the absorption of mexiletine and thus reduce the antiarrhythrnic effect of the latter. The depressant effects of codeine are enhanced by depressants of the central nervous system such as hypnotics, sedatives, tricyclic antidepressants and phenothiazines. Codeine may antagonise the gastrointestinal effects of metoclopramide and domperidone.
4.6 Fertility, pregnancy and lactation
The safety of Muscular Pain Relief during pregnancy has not been established and in view of the possible association of codeine with respiratory depression and heart malformations, use 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.
4.7 Effects on ability to drive and use machines
No adverse effects known.
4.8 Undesirable effects
The most common side effects are nausea, vomiting, constipation, insomnia, anxiety, dry mouth, sweating and palpitations. Adverse reactions to paracetamol are rare but skin rashes and other allergic reactions may occur. There have been reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol.
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.
If any of the following occur stop taking the medicine and seek medicinal attention immediately:
Slow or shallow breathing, confusion, sleepiness, small pupils, feeling or being sick, constipation and loss of appetite.
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 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 24 hours from ingestion should be discussed with the NPIS or a liver unit.
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.
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 arrhythmia.
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.
5.1 Pharmacodynamic properties
Paracetamol is an analgesic with antipyretic activity.
Caffeine is a central nervous system stimulant and contributes to the feeling of well being.
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
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 pre-clinical data of relevance to the prescriber which are additional to that included in other sections of the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Citric acid monohydrate pdr
Sodium saccharin pdr Refined sugar
Sodium bicarbonate coarse gran Anhydrous sodium carbonate Sodium benzoate Sodium metabisulphite Gelatin
6.2 Incompatibilities
None known.
Shelf life
6.3
36 months.
6.4 Special precautions for storage
Do not store above 25°C.
Store in the original package.
6.5 Nature and contents of container
Blister of nylon/aluminium/polyethylene laminate backed with aluminium/polyethylene laminate packed in a cardboard carton.
Pack sizes: 12, 24, 32 tablets.
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Max Remedies Limited William Nadin Way Swadlincote Derbyshire DE11 0BB
8 MARKETING AUTHORISATION NUMBER(S)
PL 31308/0021
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
30/11/2005
10
DATE OF REVISION OF THE TEXT
03/01/2014