Soluble Cupanol-Co Lemon Flavour
SUMMARY OF PRODUCT CHARACTERISTICS 1 NAME OF THE MEDICINAL PRODUCT
Soluble Cupanol-Co Lemon Flavour
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Soluble Cupanol-Co Lemon Flavour contain:
Paracetamol BP 500mg Codeine Phosphate BP 8mg
Excipients with known effect:
Each tablet contains 430.1 mg sodium For the full list of excipients, see section 6.1
3 PHARMACEUTICAL FORM
Effervescent Tablets
White to off white round, flat, beveled edged plain on both sides.
4.1 Therapeutic indications
For the relief of mild to moderate pain including headache, migraine, neuralgia, toothache, sore throat, muscular and periods pains.
The symptomatic relief of influenza, feverishness and colds.
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).
4.2 Posology and method of administration
For oral administration.
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.
Adults
One to two tablets to be taken every four hours if necessary. Do not exceed 8 tablets in 24 hours.
Elderly Patients
Normal adult dose unless there is impaired kidney or liver function.
Paediatric Population
Children aged less than 12 years
This product is not suitable for children aged less than 12 years.
Children aged 12 years to 18 years
One tablet to be taken every 4-6 hours. Do not exceed 4 tablets in 24 hours.
Codeine is not recommended for use in children under 18 years with compromised respiratory function for the symptomatic treatment of cough and cold. (see section 4.4)
Directions
The tablets must be dissolved in half a glass of water. The tablets dissolve more quickly in warm water, or if stirred.
4.3 Contraindications
• In children below the age of 12 years for the symptomatic treatment of cough and cold due to an increased risk of developing serious and life-threatening adverse reactions.
• 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 that they are CYP2D6 ultra-rapid metabolisers.
• This product contains 430.1 mg (18.7 mmols) of sodium per effervescent tablet. This may be harmful to people on a low sodium or low salt diet.
• Hypersensitivity to Paracetamol, codeine phosphate or any excipients listed in section 6.1.
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 hazard of overdose is greater in those with noncirrhotic alcoholic liver disease. Do not take with any other paracetamol containing products.
This product contains 430.1 mg (18.7 mmols) of sodium per effervescent tablet, equivalent to 21.505% of the WHO recommended maximum daily intake for sodium. The maximum daily dose of this product is equivalent to 172.04% of the WHO recommended maximum daily intake for sodium.
Soluble Cupanol-Co Lemon Flavour is considered high in sodium. This should be particularly taken into account for those on a low salt diet.
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 or 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% - 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 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.
Do not exceed the recommended dose. This product contains Paracetamol. If symptoms persist for more than 3 days, consult your doctor. If you are pregnant or breastfeeding consult your doctor before taking this preparation. Keep out of the reach of children. Care is advised in the administration of Paracetamol to patients with severe renal or severe hepatic impairment and in those with non-cirrhotic alcoholic liver disease. The hazards of overdose are greater in those with alcoholic liver disease.
The leaflet will state in a prominent position in the 'before taking' section:
• Do not take for longer than directed by your prescriber
• Taking codeine regularly for a long time can lead to addiction, which might cause you to feel restless and irritable when you stop the tablets.
• Taking a painkiller for headaches too often or for too long can make them worse.
The label will state (To be displayed prominently on outer pack - not boxed):
• Do not take for longer than directed by your prescriber as taking codeine regularly for a long time can lead to addiction
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 daily use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.
4.6 Fertility, Pregnancy and lactation
Pregnancy
Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol used in the recommended dose. Codeine has been used for many years without apparent ill consequence and animal studies have not shown any hazard. Patients should follow the advice of their doctor regarding the use of this product.
Breast-feeding
Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breast feeding.
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
Patients should be advised not to drive or operate machinery if affected by dizziness or sedation.
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 ‘statutory defence’) if:
o The medicine has been prescribed to treat a medical or dental problem and
o You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and o It was not affecting your ability to drive safely
4.8 Undesirable effects
• Regular prolonged use of codeine is known to lead to addiction and tolerance.
Symptoms of restlessness and irritability may result when treatment is then stopped.
• Prolonged use of a painkiller for headaches can make them worse.
The information below lists reported adverse reactions, ranked using the following frequency classification:
Very common (>1/10); common (>1/100 to <1/10); uncommon (>1/1,000 to <1/100);
rare (>1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).
Codeine can produce typical opioid effects including constipation, nausea, vomiting, dizziness, light-headedness, drowsiness, confusion and urinary retention. The frequency and severity are determined by dosage, duration of treatment and individual sensitivity. Tolerance and dependence can occur, especially with prolonged high dosage of codeine.
There have been very rare occurrences of pancreatitis.
Immune system disorders
Hypersensitivity including skin rash may occur.
Not known: anaphylactic shock, angioedema
Blood and lymphatic system disorders
Not known: agranulocytosis, thrombocytopenia
Skin and subcutaneous tissue disorders
Very rare cases of serious skin reactions have been reported.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization 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
Symptoms
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, or
• regularly consumes ethanol in excess of recommended amounts, or
• 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, gastrointestinal bleeding 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 serious hepatic dysfunction beyond 24h from ingestion should be discussed with the NPIS or a liver unit.
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 350mg or a child more than 5mg/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.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Anilides, Paracetamol combinations
ATC Code: N02B E51
Paracetamol is a well-established analgesic and antipyretic.
Codeine is a centrally weak acting 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 rapidly and almost completely absorbed from the gastrointestinal tract. Concentration in plasma reaches a peak in 30-60 minutes. Plasma half-life is 1-4 hours. Paracetamol is relatively uniformly distributed throughout most body fluids, plasma protein binding is variable.
Codeine phosphate is well absorbed after oral administration and is widely distributed. About 86% is excreted in the urine in 24 hours, 40-70% is free or conjugated morphine and 10-20% is free or conjugated Norcodeine.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction and development.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium Bicarbonate Sodium Carbonate (Anhydrous)
Sodium Cyclamate 1968 Sodium Saccharin Citric Acid Anhydrous Polyethylene Glycol Powder 6000 Povidone
Lemon F-O-L 610406E
6.2 Incompatibilities
None stated.
6.3 Shelf life
Two years.
6.4 Special precautions for storage
Store in a cool dry place.
6.5 Nature and contents of container
Strip pack using PPFM laminate, constructed of: 40gsm MGBK paper / l2gsm LDPE 8p aluminium foil / 23gsm LDPE. Strips are packed into a carton containing either 10, 12, 16, 24, 30, 36, 50, 56, 100, or 112 tablets.
6.6 Special precautions for disposal
None stated
7 MARKETING AUTHORISATION HOLDER
ACCORD HEALTHCARE LIMITED GROUND FLOOR, SAGE HOUSE 319 PINNER ROAD HARROW HA1 4HF
UNITED KINGDOM
8 MARKETING AUTHORISATION NUMBER(S)
PL 20075/0516
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
11/03/2009
10 DATE OF REVISION OF THE TEXT
09/11/2016