This information is intended for use by health professionals
Co-codamol 60/1000mg Film-coated Tablets
Each film-coated tablet contains 60mg Codeine Phosphate Hemihydrate and 1000mg Paracetamol
Excipient with known effect: Each film-coated tablet contains 5.85mg lecithin soya (E322).
For the full list of excipients, see section 6.1
Co-codamol Film-coated tablets are white, oval, 10.7 x 21.4mm, biconvex tablets, marked '10 6' on one side with a score line and side scores.
The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.
For the relief of moderate to severe pain in adults and adolescents 16 years and older.
Codeine is indicated in patients 16 years and older for the treatment of acute moderate pain which is not considered to be relieved by other analgesics such as paracetamol or ibuprofen (alone).
Prior to starting treatment with opioids, a discussion should be held with patients to put in place a strategy for ending treatment with Co-codamol in order to minimise the risk of addiction and drug withdrawal syndrome (see section 4.4).
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.
This presentation is reserved for use in adults and in adolescents over 50kg of body weight aged 16 years and above.
Adults over 18 years: One tablet not more frequently than every 4 hours, up to a maximum of 4 tablets in any 24 hour period.
Adolescents over 50kg of body weight aged 16 years and above:
One tablet not more frequently than every 6 hours, up to a maximum of 4 tablets in any 24 hour period.
Maximum daily dose:
• The maximum daily dose of Paracetamol must not exceed 4000 mg.
• Maximum single dose is 1000 mg (1 tablet).
Elderly: As adults, however a reduced dose may be required. See warnings.
In case of renal insufficiency the dose should be reduced due to available data on the paracetamol component:
10 – 50 ml/min
One Co-codamol 30mg /500mg tablet every 6 hours*
< 10 ml/min
One Co-codamol 30mg /500mg tablet every 8 hours*
* Co-codamol 30mg /500mg tablets are available for the above cases.
Paracetamol should be used with caution in the presence of hepatic insufficiency.
Chronic alcohol consumption may lower the paracetamol toxicity threshold. In these patients, the length of time between two doses should be a minimum of 8 hours. 2 g paracetamol per day should not be exceeded.
Paediatric population: Co-codamol should not be used in children below the age of 16 due to the risk of paracetamol poisoning. Also, codeine should not be used in children below the age of 16 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).
Method of administration
Co-codamol Film-coated tablets are for oral use.
- Hypersensitivity to the active substances, soya or peanut or to any of the excipients listed in section 6.1
- 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.
Conditions where morphine and opioids are contraindicated e.g.:
- Acute asthma
- Respiratory depression
- Acute alcoholism
- Hepatic failure
- Head injuries
- Raised intra-cranial pressure
- Following biliary tract surgery
- Monoamine oxidase inhibitor therapy, concurrent or within 14 days.
Drug dependence, tolerance and potential for abuse
For all patients, prolonged use of this product may lead to drug dependence (addiction), even at therapeutic doses. The risks are increased in individuals with current or past history of substance misuse disorder (including alcohol misuse) or mental health disorder (e.g., major depression).
Additional support and monitoring may be necessary when prescribing for patients at risk of opioid misuse.
A comprehensive patient history should be taken to document concomitant medications, including over-the-counter medicines and medicines obtained on-line, and past and present medical and psychiatric conditions.
Patients may find that treatment is less effective with chronic use and express a need to increase the dose to obtain the same level of pain control as initially experienced. Patients may also supplement their treatment with additional pain relievers. These could be signs that the patient is developing tolerance. The risks of developing tolerance should be explained to the patient.
Overuse or misuse may result in overdose and/or death. It is important that patients only use medicines that are prescribed for them at the dose they have been prescribed and do not give this medicine to anyone else.
Patients should be closely monitored for signs of misuse, abuse, or addiction.
The clinical need for analgesic treatment should be reviewed regularly.
Drug withdrawal syndrome
Prior to starting treatment with any opioids, a discussion should be held with patients to put in place a withdrawal strategy for ending treatment with Co-codamol.
Drug withdrawal syndrome may occur upon abrupt cessation of therapy or dose reduction. When a patient no longer requires therapy, it is advisable to taper the dose gradually to minimise symptoms of withdrawal. Tapering from a high dose may take weeks to months.
The opioid drug withdrawal syndrome is characterised by some or all of the following: restlessness, lacrimation, rhinorrhoea, yawning, perspiration, chills, myalgia, mydriasis and palpitations. Other symptoms may also develop including irritability, agitation, anxiety, hyperkinesia, tremor, weakness, insomnia, anorexia, abdominal cramps, nausea, vomiting, diarrhoea, increased blood pressure, increased respiratory rate or heart rate.
If women take this drug during pregnancy, there is a risk that their newborn infants will experience neonatal withdrawal syndrome.
Hyperalgesia may be diagnosed if the patient on long-term opioid therapy presents with increased pain. This might be qualitatively and anatomically distinct from pain related to disease progression or to breakthrough pain resulting from development of opioid tolerance. Pain associated with hyperalgesia tends to be more diffuse than the pre-existing pain and less defined in quality. Symptoms of hyperalgesia may resolve with a reduction of opioid dose.
Where analgesics are used long-term (> 3 months) with administration every two days or more frequently, headache may develop or worsen. Headache induced by overuse of analgesics (MOH – medication-overuse headache) should not be treated by dose increase. In such cases, the use of analgesics should be discontinued in consultation with the doctor.
Paracetamol/codeine should be used with caution in patients with:
- opioid-dependent patients
- prostatic hypertrophy
- adrenocortical insufficiency
- severe hepatic haemolytic anaemia
Paracetamol/codeine should be used with the outmost caution and in reduced doses in malnourished or dehydrated patients.
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.
Administration of doses higher than that recommended poses a risk of severe liver damage. Antidote treatment should be administered as quickly as possible (see section 4.9).
Estimates of prevalence of ultra-rapid metabolisers in different populations are summarized below:
3.4% to 6.5%
1.2% to 2%
3.6% to 6.5%
Risk from concomitant use of sedative medicines such as benzodiazepines or related drugs
Concomitant use of codeine and sedative medicines such as benzodiazepines or related drugs may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing with these sedative medicines should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe codeine concomitantly with sedative medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible.
The patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their caregivers to be aware of these symptoms (see section 4.5).
Risks from concomitant use of opioids and alcohol:
Concomitant use of opioids, including codeine, with alcohol may result in sedation, respiratory depression, coma and death. Concomitant use with alcohol is not recommended (see section 4.5).
Care should be observed in administering the product to any patient whose condition may be exacerbated by opioids, particularly the elderly, who may be sensitive to their central and gastro-intestinal effects, those on concurrent CNS depressant drugs, those with prostatic hypertrophy and those with inflammatory or obstructive bowel disorders. Care should also be observed if prolonged therapy is contemplated.
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 alcoholic liver disease.
Patients should be advised not to exceed the recommended dose and not take other paracetamol containing products concurrently.
Patients should be advised to consult a doctor should symptoms persist and to keep the product out of the reach and sight of children.
Caution is advised in patients with underlying sensitivity to aspirin and/or to non-steroidal anti-inflammatory drugs (NSAIDs).
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.
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 pain killer for headaches too often or for too long can make them worse.
The leaflet will state in the “pregnancy and breast-feeding” subsection of the section 2 “Before taking your medicine”:
Co-codamol is contraindicated in breast-feeding
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.
The following combinations with Co-codamol should be avoided
The following combinations with Co-codamol may require dose adjustment:
- enzyme-inducing medications such as certain antiepileptics (phenytoin, phenobarbital, carbamazepine)
- St John's wort (Hypericum perforatum)
Oral contraceptives may increase its rate of clearance.
The depressant effects of codeine may be enhanced by other central nervous system depressants: anxiolytics, hypnotics, phenothiazines, antidepressants, antipsychotics, antihistamines, other opioid analgesics, tranquilisers and alcohol. If combined therapy is necessary, the dose of one or both agents should be reduced. Alcohol should be avoided.
Sedative medicines such as benzodiazepines or related drugs:
The concomitant use of opioids with sedative medicines such as benzodiazepines or related drugs increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. The dose and duration of concomitant use should be limited (see section 4.4).
Concurrent use of anticholinergic and codeine may produce paralytic ileus.
Codeine is probably active through being O-demethylated to morphine via the enzyme CYP2D6. This bioactivation is inhibited by certain enzyme-inhibiting medications, e.g. quinidine, terbinafine, certain antidepressants and neuroleptics, etc - an interaction which has been documented in studies on healthy trial subjects and/or pilot studies on patients. These drugs therefore reduce the effect of codeine and these combinations may require a dose adjustment.
Enzyme-inducing medications such as rifampicin, barbiturates, several antiepileptics, St John's wort (Hypericum perforatum), etc. can reduce plasma concentrations of morphine (see also interaction with paracetamol below).
Alcohol and opioids:
The concomitant use of alcohol and opioids increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. Concomitant use with alcohol is not recommended (see section 4.4).
The anticoagulant effect of warfarin and other coumarins may be enhanced by regular use of paracetamol with increased risk of bleeding. The effect may occur already at daily doses of 2000 mg after 3 days. Occasional doses have no significant effect on bleeding tendency. Increased monitoring of INR values should be done during the duration of the combination and after its discontinuation.
Use of substances that induce liver enzymes, such as carbamazepine, phenytoin, phenobarbital, rifampicin and St John's wort (Hypericum perforatum) can increase the hepatotoxicity of paracetamol due to increased and more rapid formation of toxic metabolites. Therefore, caution should be taken in case of concomitant use of enzyme inducing substances.
Probenecid nearly halves the clearance of paracetamol by inhibiting its conjugation with glucuronic acid. This probably means that the dose of paracetamol can be halved when being given at the same time as probenecid.
Concurrent intake of medicinal products that accelerate gastric emptying, such as metoclopramide or domperidone, accelerates the absorption and onset of effect of paracetamol.
The absorption of paracetamol is reduced by cholestyramine. Cholestyramine should not be given within one hour if maximum analgesic effect is to be obtained.
Oral contraceptives may increase the rate of clearance of paracetamol.
Paracetamol may affect the pharmacokinetics of chloramphenicol. Therefore an analysis of chloramphenicol in plasma is recommended in the event of combination treatment with chloramphenicol for injection.
Co-codamol should be used with caution during pregnancy since codeine metabolites cross the placenta.
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. Paracetamol can be used during pregnancy if clinically needed however it should be used at the lowest effective dose for the shortest possible time and at the lowest possible frequency.
Regular use during pregnancy may cause drug dependence in the foetus, leading to withdrawal symptoms in the neonate.
If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
Administration during labour may depress respiration in the neonate and an antidote for the child should be readily available.
As a precautionary measure, the use of Co-codamol should be avoided during the third trimester of pregnancy and during labour.
This product is contraindicated during breastfeeding as codeine may be secreted in breast milk and may cause respiratory depression in the infant. (see section 4.3).
Paracetamol is excreted in breast milk but not in a clinically significant amount.
If the patient is an ultra-rapid metaboliser of CYP2D6, higher levels of the active metabolite of codeine, 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.
There is no information relating to the effects of Co-codamol on fertility.
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:
- 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.
Codeine can produce typical opioid effects including constipation, nausea, vomiting, dizziness, light-headedness, confusion, drowsiness 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.
• 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 frequency of undesirable effects is classified as follows: 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).
Blood and lymphatic system disorders
Thrombocytopaenia, haemolytic anaemia, agranulocytosis, leukopaenia.
Immune system disorders
Anaphylactic shock, angioedema.
Drug dependence (see section 4.4)
Nervous system disorders
Disturbances of vision.
Bouts of perspiration.
Respiratory, thoracic and mediastinal disorders
Bronchospasm (see section 4.4).
Nausea, constipation, vomiting.
Dryness of the mouth.
Hepatotoxicity, liver damage which may lead to liver failure.
Skin and subcutaneous tissue disorders
Rash, urticaria erythema.
Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), fixed drug eruption.
Renal and urinary disorders
Renal damage (may occur in long-term therapy.)
General disorders and administration site conditions
Drug withdrawal syndrome
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 Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
The effects of codeine overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs.
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 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 350 mg or a child more than 5 mg/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.
Immediate medical advice should be sought in the event of overdosage because of the risk of irreversible liver damage.
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 and this may be manifested in increasing pro-thrombin time, which is a reliable indicator of deteriorating liver function. Increased levels of hepatic transaminases, lactate dehydrogenase and bilirubin may occur and the INR may increase. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema, coma, 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, pancreatitis and pancytopenia have been reported.
Liver damage is likely in adults who have taken 10g or more of Paracetamol. Acute or chronic ingestion of Paracetamol above the recommended dose may lead to liver damage particularly if the patient has the following risk factors.
If the patient:
a) Is on long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John's Wort or other drugs that induce liver enzymes.
b) Regularly consumes ethanol in excess of recommended amounts.
c) Is likely to be glutathione deplete e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.
It is considered that excess quantities of toxic metabolite (usually adequately detoxified by glutathione when normal doses of Paracetamol are ingested), become irreversibly bound to liver tissue.
Immediate treatment is essential in the management of Paracetamol overdose. Despite lack of significant early symptoms, patients should be referred to hospital urgently for immediate 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 concentrations should be measured at 4 hours or later after ingestion (earlier concentrations are unreliable).
Or any patient who have ingested about 7.5g or more of Paracetamol in the preceding 4 hours should undergo gastric lavage. Plasma paracetamol concentrations 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. General supportive measures must be available.
Management of patients who present with serious hepatic dysfunction beyond 24 hours from ingestion should be discussed with the NPIS or a liver unit.
Pharmacotherapeutic group: codeine and paracetamol.
ATC Code: N02AJ06
Paracetamol has both analgesic and antipyretic effects. However, it does not have an anti-inflammatory effect. The mechanism of analgesic action has not been fully determined. The main action of paracetamol is the inhibition of cyclo-oxygenase, an enzyme which is important for the prostaglandin synthesis. Central nervous system cyclo-oxygenase is more sensitive for paracetamol than peripheral cyclo-oxygenase and this explains why paracetamol has an antipyretic and analgesic efficacy. Paracetamol probably produces antipyresis by acting centrally on the hypothalamic heat regulating centre.
Codeine is a centrally acting weak analgesic. Codeine exerts its effect through a low affinity to μ opioid receptors and its analgesic effect is due to its conversion to morphine. It can potentiate the effect of other analgesics. Codeine, particularly in combination with other analgesics such as paracetamol, has been shown to be effective in acute nociceptive pain.
Codeine phosphate has antitussive effects.
Large doses can produce excitement rather than depression.
Following oral administration of two capsules (ie, a dose of paracetamol 1000mg and codeine phosphate 60mg) the mean maximum plasma concentrations of paracetamol and codeine phosphate were 17.5 µg/ml and 327ng/ml respectively. The mean times to maximum plasma concentrations were 1.03 hours for paracetamol and 1.10 hours for codeine phosphate.
The mean AUC(0-10) following administration was 48.0µg/ml per hour for paracetamol and 1301ng/ml per hour for codeine.
The bioavailabilities of paracetamol and codeine when given as the combination are similar to those when they are given separately.
In adults paracetamol is metabolized in the liver following two major metabolic pathways: glucuronic acid (~60 %) and sulphuric acid (~35 %) conjugates. The latter route is rapidly saturated at doses higher than the therapeutic dose. A minor route, catalyzed by the cytochrome P450, results in the formation of an intermediate reagent (N-acetyl-p-benzoquinoneimine) which under normal conditions of use is rapidly detoxified by glutathione and eliminated in the urine, after conjugation with cystein (~3 %) and mercaptopuric acid. In neonates and children <12 years sulphate conjugation is the main elimination route and glucuronidation is lower than in adults. Total elimination in children is comparable to that in adults, due to an increased capacity for sulphate conjugation.
Codeine is mainly metabolized by glucuronidation to codeine-6-glucuronide. Minor routes of metabolism include O- demethylation leading to morphine, N-demethylation to norcodeine and after both O- and N-demethylation formation of normorphine. Morphine and norcodeine are further transformed in glucuroconjugates. Unchanged codeine and its metabolites are mainly excreted by urinary route within 48h (84.4±15.9%).
The O-demethylation of codeine to morphine is catalyzed by the cytochrome P450 isozyme 2D6 (CYP2D6) which shows genetic polymorphism that may affect the efficacy and toxicity of codeine.
Genetic polymorphism in CYP2D6 leads to ultra-rapid, extensive and poor metaboliser phenotypes.
Elimination of paracetamol is essentially through the urine. 90% of the ingested dose is eliminated via the kidneys within 24 hours, predominantly as the glucuronide (60 to 80 %) and the sulphate (20 to 30%) conjugates. Less than 5% is eliminated in unchanged form. The elimination half life is about 2 hours. In cases of renal or hepatic insufficiency, after overdose, and in neonates the elimination half life of paracetamol is delayed. The maximum effect is equivalent with plasma concentrations. In cases of severe renal insufficiency (creatinine clearance lower than 10 ml/min) the elimination of paracetamol and its metabolites is delayed. For elderly patients, the capacity for conjugation is not modified.
Only 4 to 12% of a given codeine dose is excreted unchanged in urine. The major part (60%) is excreted as codeine-6-glucuronide, morphine is excreted as morphine-3- glucuronide. The other metabolites found in urine were norcodeine and norcodeine- glucuronide and further minor metabolites, normorphine and hydrocodone, have also been identified. The total 8 h urinary recovery of drug-related material was 74 ± 24% in the Caucasians and 60 ± 14% in the Chinese (p < 0.001). The plasma half-life of codeine is 3-3.5 h in adults. Effect is remained for 4 – 6 hours.
Codeine phosphate has log-linear kinetics in the elimination phase.
Just under 10 % of the population is unable to convert codeine to morphine, which is why such individuals will not benefit from the codeine content of the tablets.
Elderly patients may metabolise codeine more slowly than younger ones. Dose adjustment may be considered.
Conventional studies using the currently accepted standards for the evaluation of toxicity to reproduction and development are not available.
Silica colloidal anhydrous
Hydroxypropylated starch (E1440)
Lecithin soya (E322)
Titanium dioxide (E171)
Shelf life after first opening of the HDPE container: 100 days
This medicinal product does not require any special storage conditions
White PVC/Aluminium blisters
or white PVC/Aluminium/PE/paper child resistant blisters
or white HDPE tablet container with a white LDPE cap
or white HDPE tablet container with a white PP child-resistant screw cap.
Blisters: 8, 10, 16, 20, 24, 30, 40, 50 and 100 film-coated tablets
Tablet containers: 50 and 100 film-coated tablets
Not all pack sizes may be marketed.
No special requirements.
(Trading style: Accord)