CO-CODAMOL

Treatment goals and discontinuation Before initiating treatment with Co-codamol, 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). Posology Duration of treatment The duration of treatment should be limited to 3 days. 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.

Adults:

The usual dose is two tablets every six hours as required. The total daily dose should not exceed 4g paracetamol (8 tablets in a day). Codeine should be used at the lowest effective dose for the shortest period of time. This dose may be taken, up to 4 times a day at intervals of not less than 6 hours.

The total daily dose should not exceed 120 mg codeine (8 tablets in a day). 4).

Paediatric population:

Children aged 16 to 18 years: Two tablets to be taken every six hours as required, up to a maximum of eight tablets in any 24-hour period.

Children aged 12 to 15 years:

One tablet to be taken every six hours as required, up to a maximum of four tablets in any 24-hour period. 4). Method of administration Oral. The tablets should be placed in a glass of water and allowed to be dissolved completely. The resulting solution should be drunk immediately.

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. Prolonged use of a painkiller for headaches can make them worse. Adverse effects of paracetamol are rare. 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).

System organ class Frequency Adverse effects Blood and lymphatic system disorders Very rare Not known Thrombocytopenia, Neutropenia, Leucopenia. Agranulocytosis. Immune system disorders Rare Not known Hypersensitivity including skin rash may occur.

Anaphylactic shock, Angioedema. Metabolism and nutrition disorders Not known High anion gap metabolic acidosis. 4). Vascular disorders Not known Hypotension (with high doses). 4). Gastrointestinal disorders Very rare Pancreatitis. Hepatobiliary disorders Not known Sphincter of Oddi dysfunction Skin and subcutaneous tissue disorders Very rare Very rare cases of serious skin reactions have been reported.

4). Pyroglutamic acidosis may occur as a consequence of low glutathione levels in these patients. Drug dependence Repeated use of Co-codamol can lead to drug dependence, even at therapeutic doses. 4). Symptoms of restlessness and irritability may result when treatment is then stopped.

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.

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. 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 Co- codamol.

Repeated use of Co-codamol 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 Co-codamol may result in overdose and/or death. g. major depression, anxiety and personality disorders).

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 online, 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. 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.

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.

Symptoms of hyperalgesia may resolve with a reduction of opioid dose. 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 ultra-rapid metaboliser there is an increased risk of developing side effects of opioid toxicity even at low doses 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, shallow breathing, small pupils, nausea, vomiting, constipation, lack of appetite and somnolence.

In severe cases this may include symptoms of circulatory and respiratory depression, which may be life-threatening and very rarely fatal. 9% Northern European 1%-2% Hepatobiliary disorders Codeine may cause dysfunction and spasm of the sphincter of Oddi, thus increasing the risk of biliary tract symptoms and pancreatitis.

Therefore, codeine/paracetamol has to be administered with caution in patients with pancreatitis and diseases of the biliary tract. Sleep-related breathing disorders Opioids can cause sleep-related breathing disorders including central sleep apnoea (CSA) and sleep-related hypoxemia.

Opioid use […]

1. 6); monoamine oxidase inhibitor therapy, concurrent or within 14 days. 4). In patients for whom it is known they are CYP2D6 ultra-rapid metaboliser.