Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2020 Publisher: Galen Limited, Seagoe Industrial Estate, Craigavon, BT63 5UA, UK
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.
This product is contraindicated in patients with raised intracranial pressure or head injury, respiratory depression, acute asthma and acute alcoholism.
Kapake/Co-Codamol 30mg/500mg Tablets are also contraindicated in patients receiving monoamine oxidase inhibitors or who have received these agents within the previous two weeks (see section 4.5).
This product is contraindicated in women during breast-feeding (see section 4.6) and also in patients for whom it is known they are CYP2D6 ultra-rapid metabolisers.
Kapake/Co-Codamol 30mg/500mg Tablets are contraindicated 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).
Kapake/Co-Codamol 30mg/500mg Tablets are not recommended for children under 12 years of age.
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. Estimates of prevalence of ultra-rapid metabolisers in different populations are summarised below:
| Population | Prevalence % |
|---|---|
| African/Ethiopian | 29% |
| African American | 3.4% to 6.5% |
| Asian | 1.2% to 2% |
| Caucasian | 3.6% to 6.5% |
| Greek | 6.0% |
| Hungarian | 1.9% |
| Northern European | 1% to 2% |
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.
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 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.
Concomitant use of Kapake/Co-Codamol 30mg/500mg Tablets 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 Kapake/Co-Codamol 30mg/500mg Tablets concomitantly with sedative medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible.
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).
Kapake/Co-Codamol 30mg/500mg Tablets should be used with caution in the elderly and debilitated as these patients may be more sensitive to the effects of opioids, those with prostatic hypertrophy, inflammatory or obstructive bowel disorders or Addison’s disease.
Care is advised in the administration of paracetamol to patients with severe renal or severe hepatic impairment.
Opioid analgesics should be given with caution or in reduced doses to patients with renal or hepatic impairment (and avoided if the impairment is severe).
The hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease.
Immediate medical advice should be sought in the event of an overdose, even if the patient feels well, because of the risk of delayed serious liver damage. Patients should be advised not to take other paracetamol-containing products concurrently.
Do not exceed the recommended dose. If symptoms persist, consult your doctor. Keep out of the reach of children.
The leaflet will state in a prominent position in the ‘before taking’ section:
The label will state (to be displayed prominently on outer pack – not boxed):
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.
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.
Kapake/Co-Codamol 30mg/500mg Tablets are contraindicated in patients receiving monoamine oxidase inhibitors or who have received these agents within the previous two weeks (see section 4.3).
The concomitant use of opioids with sedative medicines such as benzodiazepines or related drugs (including anxiolytics, hypnotics, antidepressants and antipsychotics) increases the risk of sedation, respiratory depression, coma and death because of additive central nervous system (CNS) depressant effects. The dose and duration of concomitant use should be limited (see section 4.4). Alcohol should be avoided.
The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by colestyramine.
The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.
This product should not be used during pregnancy.
Regular use during pregnancy may cause drug dependence in the foetus, leading to withdrawal symptoms in the neonate.
Administration during labour may depress respiration in the neonate.
Codeine should not be used during breast-feeding (see section 4.3).
Administration to nursing women is not recommended as codeine may be secreted in breast milk and may cause respiratory depression in the infant.
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.
Codeine may impair mental and/or physical abilities, therefore it may affect the ability to drive and operate machinery.
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:
Adverse effects of paracetamol are rare but hypersensitivity including skin rash may occur. Very rare cases of serious skin reactions have been reported. There have been reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol.
The most common adverse effects to codeine are dizziness, drowsiness, nausea and vomiting. These effects are often more common in the ambulatory patient and thus may be alleviated if the patient lies down. Other side effects to codeine which may occur include constipation, urinary retention, light headedness, confusion, euphoria, dysphoria, miosis, bradycardia, abdominal pain (rarely codeine-induced pancreatitis has been reported in patients with a history of cholecystectomy), allergic reactions and pruritus.
Regular prolonged use of codeine is known to lead to drug dependence (see section 4.4). Drug withdrawal syndrome may occur when treatment is stopped.
Prolonged use of a painkiller for headaches can make them worse.
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.
Not applicable.
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