Co-codamol 30mg/500mg/5ml Oral Solution – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

Co-codamol 30mg/500mg/5ml Oral Solution

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Co-codamol Oral Solution contains 30 mg of Codeine Phosphate and 500 mg of Paracetamol in each 5 mL.

Excipients with known effect

Glycerol 1.5 g/5mL

Propylene Glycol 1.65 g/5mL

Methylparahydroxybenzoate 9 mg/5mL

Propylparahydroxybenzoate 1 mg/5mL

For the full list of excipients see section 6.1.

3 PHARMACEUTICAL FORM

Oral solution.

Clear, brown solution.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Codeine is indicated in patients older than 12 years of age for the treatment of acute moderate pain which is not considered to be relieved by other analgesics such as paracetamol or ibuprofen (alone).

4.2 Posology and method of administration

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. In absence of adequate pain control, the possibility of hyperalgesia, tolerance and progression of underlying disease should be considered (see section 4.4).

Duration of treatment

Co-codamol should not be used longer than necessary.

Posology

For oral use.

Adults and young persons 16 years and over

The optimal dosage range is 30mg/500mg (5mL) to 60mg/1000mg (10mL) up to three to four times per day.

Young persons 12-15 years

The optimal dosage range is 30mg/500mg (5mL) to 45mg/750mg (7.5mL) up to three to four times per day.

The dose should not be repeated more frequently than every 4-6 hours, and not more than four doses should be taken in any 24 hour period.

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.

Elderly

The dosage should be reduced.

Hepatic impairment

The dosage should be reduced.

Paediatric population

Codeine should not be used in children below the age of 12 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

The recommended dose for adults and children over 15 years is one or two 5 mL doses (5mL to 10mL) every four to six hours with a maximum dose of eight 5mL in any 24 hour period.

The recommended dose for young persons aged 12 -15years is one or one and a half 5 mL doses (5mL to 7.5mL) every four to six hours with a maximum of four doses in any 24 hour period.

Dosage should be adjusted accordingly to the severity of the pain and the response of the patient. However, it should be kept in mind that tolerance to codeine can develop with continued use and that the incidence of untoward effects is dose related. Doses of codeine higher than 60 mg fail to give commensurate relief of pain but merely prolong analgesia and are associated with an appreciable increased incidence of undesirable side effects.

4.3 Contraindications

i. Paracetamol:

• Hypersensitivity to paracetamol or any of the excipients.

ii. Codeine:

• Acute respiratory depression
• Hypersensitivity to codeine or other opioid analgesics, or to any of the excipients.
• Liver disease.
• Acute alcoholism.
• Use should be avoided in patients with raised intracranial pressure or head injury (in addition to the risk of respiratory depression and increased intracranial pressure, may affect pupillary and other responses vital for neurological assessment).
• 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
• Concomitant use of monoamine oxidase inhibitors (MAOIs) or within two weeks of MAOI discontinuation as severe CNS excitation or depression (including hypertension or hypotension) may occur.

Codeine is also contraindicated in conditions where:

• inhibition of peristalsis is to be avoided,
• there is a risk of paralytic ileus,
• abdominal distension develops,
• acute diarrhoeal conditions such as acute ulcerative colitis or antibiotic associated colitis (e.g. pseudomembranous colitis)

Not to be used in children of 12 years and under.

4.4 Special warnings and precautions for use

Co-codamol 30mg/500mg/5ml Oral Solution may cause drowsiness. Co-codamol 30mg/500mg/5ml Oral Solution should be given in reduced doses or with caution to elderly patients or debilitated patients or patients with hypothyroidism, asthma, decreased respiratory reserve, adrenocortical insufficiency, prostatic hypertrophy, hypotension, shock, inflammatory or obstructive bowel disorders, urethral stricture, convulsive disorders, myasthenia gravis. It should be avoided or the dose reduced in patients with hepatic or renal impairment.

Avoid use during an acute asthma attack.

Risks from concomitant use of opioids and benzodiazepines

Concomitant use of opioids, including codeine, with benzodiazepines may result in sedation, respiratory depression, coma and death. Because of these risks, reserve concomitant prescribing of opioids and benzodiazepines for use in patients for whom alternative treatment options are inadequate. If a decision is made to prescribe codeine concomitantly with benzodiazepines, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of sedation and respiratory depression (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

CYP2D6 metabolism

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 summarized below:

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.

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 has to be administered with caution in patients with pancreatitis and diseases of the biliary tract.

Administration of pethidine and possibly other opioid analgesics to patients taking a monoamine oxidase inhibitor (MAOI) has been associated with very severe and sometimes fatal reactions. If the use of codeine is considered essential then great care should be taken in patients taking MAOIs or within 14 days of stopping MAOIs (see section 4.5).

Caution should be exercised when using paracetamol prior to (less than 72 hours) or concurrently with intravenous busulfan (see section 4.5 Interactions).

Co-codamol 30mg/500mg/5ml Oral Solution enhance the effects of alcohol. Concurrent use should be avoided.

The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease.

Patients should be advised that immediate medical advice should be sought in the event of an overdose, because of the risk of delayed, serious liver damage. They should be advised not to take other paracetamol-containing products concurrently and to keep the product out of the reach of children.

The risk-benefit of continued use should be assessed regularly by the prescriber.

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. The risk of developing OUD is increased in patients with a personal or a family history (parents or siblings) of substance use disorders (including alcohol use disorder), in current tobacco users or in patients with a personal history of other mental health disorders (e.g. major depression, anxiety and personality disorders).

Before initiating treatment with co-codamol and during the treatment, treatment goals and a discontinuation plan should be agreed with the patient (see section 4.2). 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.

Patients will require monitoring for signs of drug-seeking behaviour (e.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 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. A dose reduction or treatment review may be indicated.

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.

Cases of high anion gap metabolic acidosis (HAGMA) due to pyroglutamic acidosis have been reported in patients with severe illness such as severe renal impairment and sepsis, or in patients with malnutrition and other sources of glutathione deficiency (e.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.

Sleep-related breathing disorders

Opioids can cause sleep-related breathing disorders including central sleep apnoea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the total opioid dosage.

4.5 Interaction with other medicinal products and other forms of interaction

In high doses or with regular treatment, paracetamol may potentiate the effects of warfarin or other coumarins and lead to an increased risk of bleeding. The absorption of paracetamol is reduced by cholestyramine and accelerated by domperidone and metoclopramide.

Cytotoxic drugs: Paracetamol possibly inhibits metabolism of intravenous busulfan (manufacturer of intravenous busulfan advises caution within 72 hours of paracetamol).

Anaesthetics: sedative antihistamines, sodium oxybate: concomitant

administration of codeine may cause increased CNS depression and/or respiratory depression and/or hypotension.

Codeine antagonises the effect of metoclopramide and cisapride on gastrointestinal activity. It delays the absorption of flecainide and mexiletine and potentiates the effect of hypnotics and anxiolytics. The analgesic activity of codeine is likely to be significantly impaired by quinidine which impairs codeine metabolism.

Antidepressants: The depressant effects of opioid analgesics may be enhanced by tricyclic antidepressants. MAOIs taken with pethidine have been associated with severe CNS excitation or depression (including hypertension or hypotension). Although this has not been documented with codeine, it is possible that a similar interaction may occur and therefore the use of codeine should be avoided while the patient is taking MAOIs and for 2 weeks after MAOI discontinuation.

Antipsychotics: enhanced sedative and hypotensive effect.

Alcohol: the hypotensive, sedative and respiratory depressive effects of alcohol may be enhanced.

Concurrent use of codeine with antidiarrhoeal and antiperistaltic agents such as loperamide and kaolin may increase the risk of severe constipation.

Isoniazid may increase the risk of hepatotoxicity with therapeutic doses of paracetamol. Antiepileptics, such as carbamazepine, phenobarbital, phenytoin and primidone can reduce the effects of paracetamol and increase the risk of hepatotoxicity.

Concomitant use of antimuscarinics may lead to paralytic ileus or urinary retention.

Ulcer-healing drugs: Cimetidine may inhibit the metabolism of dihydrocodeine resulting in increased plasma concentrations.

Paracetamol may increase the elimination half-life of chloramphenicol. Oral contraceptives may increase its rate of clearance. The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine.

Interference with laboratory tests: Opioids may interfere with gastric emptying studies as they delay gastric emptying and with hepatobiliary imaging using technetium Tc 99m disofenin as opioid treatment may cause constriction of the sphincter of Oddi and increase biliary tract pressure.

Caution should be taken when paracetamol is used concomitantly with flucloxacillin as concurrent intake has been associated with high anion gap metabolic acidosis due to pyroglutamic acidosis, especially in patients with risks factors (see section 4.4)

Gabapentinoids: The concomitant use of co-codamol with gabapentinoids

(gabapentin and pregabalin) may result in respiratory depression, hypotension, profound sedation, coma or death (see section 4.4).

4.6 Fertility, pregnancy and lactation

Pregnancy

Use during pregnancy should be avoided, unless advised by a physician. This includes maternal use during labour because of the potential for respiratory depression in the neonate.

The safety of paracetamol-codeine during pregnancy has not been established relative to the possible adverse effects of fetal development.

There is inadequate evidence of the safety of codeine in human pregnancy. As with all medication, caution should be exercised during pregnancy, especially in the first trimester.

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.

A possible association with respiratory and cardiac malformations has been reported following first trimester exposure to codeine. Opioid analgesics may cause gastric stasis during labour, increasing the risk of inhalation pneumonia in the mother.

There is epidemiological evidence of safety in human pregnancy when paracetamol is used in normal stated dosages. 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. If clinically needed, paracetamol can be used during pregnancy however it should be used at the lowest effective dose for the shortest possible time and at the lowest possible frequency.

Breastfeeding

Administration to nursing women is not recommended as codeine may be secreted in breast milk and may cause respiratory depression in the infant.

i. Paracetamol: Paracetamol is excreted in breast milk, but not in a clinically significant amount. Available published data do not contraindicate breast-feeding.

ii. Codeine should not be used during breastfeeding (see section 4.3). 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.

If symptoms of opioid toxicity develop in either the mother or the infant, then all codeine containing medicines should be stopped and alternative non-opioid analgesics prescribed. In severe cases consideration should be given to prescribing naloxone to reverse these effects.

4.7 Effects on ability to drive and use machines

Codeine produces sedation and may also cause changes in vision, including blurred or double vision. If affected, patients should not drive or operate machinery. The effects of alcohol are enhanced by opioid analgesics.

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 of 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

4.8 Undesirable effects

List of adverse reactions

The adverse reactions reported below are classified according to frequency of occurrence 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)

Effects of withdrawal -abrupt withdrawal precipitates a withdrawal syndrome. Symptoms may include tremor, insomnia, nausea, vomiting, sweating and increase in heart rate, respiratory rate and blood pressure. NOTE tolerance diminishes rapidly after withdrawal so a previously tolerated dose may prove fatal.

Other effects -Most reports of adverse reactions to paracetamol relate to overdosage with the drug.

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.

Description of selected adverse reactions

High anion gap metabolic acidosis

Cases of high anion gap metabolic acidosis due to pyroglutamic acidosis have been observed in patients with risk factors using paracetamol (see section 4.4). 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. The risk of drug dependence may vary depending on a patient's individual risk factors, dosage, and duration of opioid treatment (see section 4.4).

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.

4.9 Overdose

Patients should be informed of the signs and symptoms of overdose and to ensure that family and friends are also aware of these signs and to seek immediate medical help if they occur.

Symptoms

Symptoms of paracetamol overdose in the first 24 hours are sweating, pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, hypotension, cerebral oedema, coma and death. Prothrombin time may increase with deteriorating liver function. Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Cardiac arrythmias and pancreatitis have been reported. Liver damage is possible in adults who have taken 10 g or more of paracetamol. It is considered that excess quantities of a toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are ingested),become irreversibly bound to liver tissue.

Treatment

Immediate treatment is essential in the management of paracetamol overdose. Despite of lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention and any patient who has ingested around 7.5 g or more of paracetamol in the proceeding 4 hours should undergo gastric lavage. Administration of oral methionine or intravenous N-acetylcysteine which may have a beneficial effect up to at least 48 hours after the overdose, may be required. General supportive measures must be available.

An overdose with codeine is characterised by respiratory depression, extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin and sometimes bradycardia and hypotension. In severe overdose with codeine, apnoea, circulatory collapse, cardiac arrest and death may occur. Primary attention should be given to the re-establishment of adequate respiratory function through the provision of a patent airway and the institution of controlled ventilation. Oxygen, intravenous fluids, vasopressors and other supportive measures should be employed as indicated. Opioid antagonists, such as naloxone may be administered.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Analgesics, ATC Code: N02B E51

Paracetamol has analgesic and antipyretic properties.

Codeine phosphate is an opioid analgesic.

Codeine is a centrally acting weak analgesic. Codeine exerts its effect through μ opioid receptors, although codeine has low affinity for these receptors, and its analgesic effect is due to its conversion to morphine. Codeine, particularly in combination with other analgesics such as paracetamol, has been shown to be effective in acute nociceptive pain.

5.2 Pharmacokinetic properties

Both paracetamol and codeine phosphate are readily absorbed from the gastro-intestinal tract giving peak plasma levels within one hour of administration.

Paracetamol is metabolised in the liver and excreted in the urine mainly as the glucuronide and sulphate conjugates. Less than 5% is excreted as unchanged paracetamol. The elimination half life varies from about one to four hours. At usual therapeutic concentrations plasma-protein binding is negligible.

Codeine is metabolised in the liver to morphine and norcodeine which are both excreted in the urine partly as conjugates with glucuronic acid. Most of the excretion products appear in the urine within six hours and up to 80% of the dose is excreted in 24 hours. About 70% of the dose is excreted as free codeine, 10% as free and conjugated morphine and a further 10% as free or conjugated norcodeine. Only traces are found in the faeces. The plasma half life is approximately three to four hours.

5.3 Preclinical safety data

There are no preclinical data of relevance to the prescriber which are additional to those included in other sections. Conventional studies using the currently accepted standards for the evaluation of toxicity to reproduction and development are not available.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Propylene Glycol (E1520)

Glycerol (E422)

Macrogol 400

Citric acid monohydrate

Sodium citrate

Sucralose

Methyl parahydroxybenzoate (E218)

Propyl parahydroxybenzoate (E216)

Ascorbic acid

Peppermint flavour

Caramel colour (E150d)

Purified water

6.2 Incompatibilities

In the absence of incompatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3 Shelf life

Unopened: 2 years

Opened: 3 months

6.4 Special precautions for storage

Store below 25ºC. Do not refrigerate or freeze. Store in the original bottle.

6.5 Nature and contents of container

Bottles: Amber (Type III) soda glass 150mL, 200mL and 500mL bottles. Bottle provided in an outer cardboard carton.

Closure: 28mm white, child-resistant tamper evident caps with expanded polyethylene (EPE) liner.

Syringe: A 5mL dispensing oral syringe and bottle adapter are supplied with this pack.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Not applicable.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

Wockhardt UK Ltd

Ash Road North

Wrexham

LL13 9UF

UK

8 MARKETING AUTHORISATION NUMBER(S)

PL 29831/0590

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

21/08/2025

10 DATE OF REVISION OF THE TEXT

02/06/2026