Summary of medicine characteristics - CODIS 500
1 NAME OF THE MEDICINAL PRODUCT
Codis 500
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
3 PHARMACEUTICAL FORM
Dispersible tablet
4 CLINICAL PARTICULARS
4.5 Interactions with other medicinal products and other forms of interaction
May enhance the effects of anticoagulants and inhibit the effects of uricosurics.
Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. However, the limitations of these data and the uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 5.1).
Metamizole may reduce the effect of acetylsalicylic acid on platelet aggregation, when taken concomitantly. Therefore, this combination should be used with caution in patients taking low dose aspirin for cardioprotection.
4.6 Pregnancy and lactation
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.
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.
There is clinical and epidemiological evidence for the safety of aspirin in human pregnancy, but it may prolong labour and contribute to maternal and neonatal bleeding and is best avoided at term in the last trimester of pregnancy and during breastfeeding.
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:
– The medicine has been taken to treat a medical or dental problem and
– You have taken it according to the information provided with the medicine and
– It was not affecting your ability to drive safely
4.8 Undesirable effects
May precipitate bronchospasm and include attacks of asthma or hypersensitivity in susceptible subjects, and may include gastrointestinal hemorrhage, occasionally major.
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 or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
The effects in overdosage will be potentiated by simultaneous ingestion of alcohol and psychotrophic drugs.
Central nervous system depression, including respiratory depression, may develop, but is unlikely to be severe unless other sedative agents have been coingested, 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.
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 1 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 4 hours after ingestion, or 8 hours if a sustained release preparation has been taken.
Salicylate poisoning is usually associated with plasma concentrations >350mg/L (2.5mmol/L). Most adult deaths occur in patients whose concentrations exceed 700mg/b (5.1mmol/L). Single doses less than 100mg/kg are unlikely to cause serious poisoning.
Common features include vomiting, dehydration, tinnitus, vertigo, deafness, sweating, warm extremities with bounding pulses, increased respiratory rate and hyperventilation. Some degree of acid-base disturbance is present in most cases.
A mixed respiratory alkalosis and metabolic acidosis with normal or high arterial pH (normal or reduced hydrogen ion concentration) is usual in adults and children over the age of 4 years. In children aged 4 years or less, a dominant metabolic acidosis with low arterial pH (raised hydrogen ion concentration) is common. Acidosis may increase salicylate transfer across the blood brain barrier.
Uncommon features include haematemesis, hyperpyrexia, hypoglycaemia, hypokalaemia, thrombocytopenia, increased INRIPTR, intravascular coagulation, renal failure and non-cardiac pulmonary oedema.
Central nervous system features, including confusion, disorientation, coma and convulsions, are less common in adults than in children.
Give activated charcoal if an adult presents within 1 hour of ingestion of more than 250mg/kg. The plasma salicylate concentration should be measured, although the severity of poisoning cannot be determined from this alone, and the clinical and biochemical features must be taken into account. Elimination is increased by urinary alkalinisation, which is achieved by the administration of 1.26% sodium bicarbonate. The urine pH should be monitored. Correct metabolic acidosis with intravenous
8.4% sodium bicarbonate (first check serum potassium). Forced diuresis should not be used since it does not enhance salicylate excretion and may cause pulmonary oedema.
Haemodialysis is the treatment of choice for severe poisoning and should be considered in patients with plasma salicylate concentrations >700mg/b (5.1mmoIIL), or lower concentrations associated with severe clinical or metabolic features. Patients under 10 years or over 70 have increased risk of salicylate toxicity and may require dialysis at an earlier stage.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Aspirin
Aspirin inhibits the cyclo-oxygenase enzyme involved in conversion of phospholipids to prostaglandins and its effect on the body are believed to result primarily from prevention of prostaglandin production. These effects include peripheral analgesia, fever reduction, reduction in inflammation and inhibition of platelet aggregation.
Codeine
Codeine is a centrally acting weak analgesic. Codeine exerts its effects through li opioid receptors although codeine has low affinity for these receptors, and its analgesic effect is due to its conversion to morphine. Its actions include analgesia, inhibition of the cough reflex and reduction in gastrointestinal motility.. Codeine, particularly in combination with other analgesics such as paracetamol, has been shown to be effective in acute nociceptive pain.
5.2 Pharmacokinetic properties
Aspirin
Aspirin is rapidly absorbed from the stomach and upper gastrointestinal tract with peak levels after around 20–30 minutes following dissolution. It is subject to first-pass metabolism with an overall bioavailability of around 70%. Metabolism is by conversion to salicylic acid and then further to other metabolites. These are excreted both free and conjugated mainly by the kidneys. The plasma half-life of aspirin is around 15–20 minutes and of salicylic acid is 2–3 hours.
Codeine
Codeine is well absorbed from the gastrointestinal tract with peak concentrations occurring after around 1 hour. Absorption is rapid and virtually complete with a bioavailability of around 60%. It is metabolised in the liver and excreted mainly in the urine as free and conjugated metabolites. The halflife of codeine in plasma is 2.5–4 hours.
5.3 Preclinical safety data
No preclinical findings of relevance to the prescriber have been reported.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Calcium carbonate
Maize starch
Citric acid
Talc
Sodium lauryl sulphate
Saccharin
6.2 Incompatibilities
None known
6.3 Shelf life
Three years
6.4 Special precautions for storage
Store below 30°C in a dry place
6.5 Nature and contents of container
Cardboard carton containing tablets in strips of 30 micron aluminium soft temper foil with the addition of a 12 micron polyester laminate on the unprinted side.
Pack sizes: 8, 12, 16, 24, 32
6.6 Special precautions for disposal
Tablets to be dissolved in water prior to administration