CO-CODAMOL

Posology 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). The duration of treatment should be as short as possible, 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 over 18 years One or two tablets not more frequently than every 4 to 6 hours, up to a maximum of 8 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 (2 tablets). Elderly As adults, however a reduced dose may be required. See section

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, neutropenia, Very rare Not known leucopenia.

Agranulocytosis. Immune system disorders 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). Hepatobiliary disorders Not known Sphincter of Oddi dysfunction. Skin and subcutaneous tissue disorders Very rare Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), fixed drug eruption.

General disorders and administration site conditions Uncommon Very rare Drug withdrawal syndrome. Panreatitis. Description of selected adverse reactions Drug dependence Repeated use of Co-codamol 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.

4. Renal insufficiency In case of renal insufficiency the dose should be reduced due to available data on the paracetamol component: Glomerulal filtration Dose 10 – 50 ml/min One Co-codamol 15 mg / 500 mg tablet every 6 hours < 10 ml/min One Co-codamol 15 mg / 500 mg tablet every 8 hours Hepatic insufficiency As adults, however a reduced dose may be required.

4. Chronic alcoholism Chronic alcohol consumption may lower the paracetamol toxicity threshold. In these patients, the dosing interval should be a minimum of 8 hours. The maximum daily dose of paracetamol should be 2 g per day. 4). Children 12 – 15 years of age One tablet every 6 hours, up to a maximum of 4 tablets in any 24 hour period.

Adolescents aged 16 years or above and over 50kg of body weight One or two tablets every 6 hours, up to a maximum of 8 tablets in any 24 hour period. Method of administration Co-codamol film-coated tablets are for oral use. 1 or soya or peanut.

6) Monoamine oxidase inhibitor therapy, concurrent or within 14 days. 4). In patients for whom it is known that they are CYP2D6 ultra-rapid metabolisers. 4 Special warnings and precautions for use 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).

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. 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.

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 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.

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.

A dose reduction or treatment review may be indicated to resolve symptoms of hyperalgesia. 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 […]

1 or soya or peanut. 6) Monoamine oxidase inhibitor therapy, concurrent or within 14 days. 4). In patients for whom it is known that they are CYP2D6 ultra-rapid metabolisers.