CODEINE/PARACETAMOL

4).

Adults:

Two tablets not more frequently than every 4 to 6 hours, up to a maximum of 8 tablets in any 24 hour period.

Elderly:

As adults, however a reduced dose may be required. See warnings.

Children aged 16 to 18 years:

One to two tablets every 6 hours when necessary to up a maximum of 8 tablets in 24 hours.

Children aged 12 to 15 years:

One tablet every 6 hours when necessary to a maximum of 4 tablets in 24 hours. 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.

The duration of treatment should be as short as possible, and if no effective pain relief is achieved the patients/carers should be advised to seek the views of a physician. 4). Method of administration Codeine/Paracetamol film-coated tablets are for oral use.

Treatment goals and discontinuation Before initiating treatment with Codeine/Paracetamol film-coated tablets, a treatment strategy including treatment duration and treatment goals, and a plan for end of the treatment, should be agreed together with the patient, in accordance with pain management guidelines.

During treatment, there should be frequent contact between the physician and the patient to evaluate the need for continued treatment, consider discontinuation and to adjust dosages if needed. When a patient no longer requires therapy with codeine, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal.

4).

8 Undesirable effects 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). Undesirable effects Blood and lymphatic system disorders Very rare Not known Thrombocytopaenia, neutropenia, leucopenia Agranulocytosis Immune system disorders Rare Not known Hypersensitivity including skin rash may occur Anaphylactic shock, angioedema.

4). Metabolism and nutrition disorders Not known High anion gap metabolic acidosis Skin and subcutaneous disorders Very rare Very rare cases of serious skin reactions have been reported. 4) Vascular disorders Not known hypotension (with high doses).

General disorders and administration site conditions Uncommon Very rare Drug withdrawal syndrome Very rare occurrence of pancreatitis. Hepatobiliary disorders Not known Sphincter of Oddi dysfunction Repeated use of Codeine/Paracetamol film-coated tablets can lead to drug dependence, even at therapeutic doses.

4). 4). Pyroglutamic acidosis may occur as a consequence of low glutathione levels in these patients. 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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Tolerance and opioid use disorder (abuse and dependence) Tolerance, physical and psychological dependence, and opioid use disorder (OUD) may develop upon repeated administration of opioids such as Codeine/Paracetamol film-coated tablets.

Repeated use of Codeine/Paracetamol film-coated tablets can lead to OUD. A higher dose and longer duration of opioid treatment can increase the risk of developing OUD. Abuse or intentional misuse of Codeine/Paracetamol film-coated tablets may result in overdose and/or death.

g. major depression, anxiety and personality disorders). 2). Before and during treatment the patient should also be informed about the risks and signs of OUD. If these signs occur, patients should contact their physician. g. too early requests for refills).

This includes the review of concomitant opioids and psycho-active drugs (like benzodiazepines). For patients with signs and symptoms of OUD, consultation with an addiction specialist should be considered. 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 codeine.

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 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.

As with other opioids, in case of insufficient pain control in response to an increased dose of codeine, the possibility of opioid-induced hyperalgesia should be considered. A dose reduction or treatment review may be indicated. CYP2D6 metabolism Codeine is partially metabolised by CYP2D6.

If a patient has a deficiency or is completely lacking this enzyme they will not obtain adequate analgesic effects. 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 nausea, vomiting, constipation, lack of appetite, somnolence, shallow breathing, small pupils and confusion.

In severe cases this may include symptoms of circulatory and respiratory depression, which may be life-threatening and very rarely fatal. 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. g. chronic alcoholism) who were treated with paracetamol at therapeutic dose for a prolonged period or a combination of paracetamol and flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, prompt discontinuation of paracetamol and close monitoring, is recommended.

The measurement of urinary 5-oxoproline may be useful to identify pyroglutamic acidosis as underlying cause of HAGMA in patients with multiple risk factors. Risks […]

Hypersensitivity to paracetamol or codeine which is rare. 6). Monoamine oxidase inhibitor therapy, concurrent or within 14 days. 4). In patients for whom it is known they are CYP2D6 ultra-rapid metabolisers.