Drugs List

Therapeutic Indications

Uses

Pain - moderate to severe

Contraindications

Acute alcohol intoxication
Children under 12 years
Risk of paralytic ileus
Acute asthma
Acute diarrhoea
Acute ulcerative colitis
CYP2D6 ultra-rapid metaboliser genotype
Head trauma
Obstructive pulmonary disease
Paralytic ileus
Pseudomembranous enterocolitis
Raised intracranial pressure
Respiratory depression
Severe hepatic disorder

Precautions and Warnings

Abdominal pain of unknown cause
Elderly
Within 2 weeks of discontinuing MAOIs
Addison's disease
Adrenal insufficiency
Alcoholic liver disease
Asthma
Benign prostatic hyperplasia
Biliary tract disorder
Breastfeeding
Cardiac arrhythmias
Dehydration
Gastrointestinal obstruction
Hepatic impairment
Hereditary fructose intolerance
History of alcohol abuse
History of drug misuse
Hypotension
Hypothyroidism
Inflammatory bowel disease
Myasthenia gravis
Pregnancy
Renal impairment
Respiratory impairment
Urethral stricture

Children under 18 years: Increased risk of rare and severe adverse effects
Hepatic cirrhosis: hepatic coma may be precipitated
Reduce dose in patients with hepatic impairment
Sodium content of effervescent preparation may be significant
Advise patient ability to drive or operate machinery may be impaired
Advise patient dizziness may affect ability to drive or operate machinery
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine may be subject to driving restrictions
Avoid within 2 weeks of discontinuing a MAOI
Not all available strengths are licensed for all indications
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some brands contain metabisulfite, may cause bronchospasm/allergies
Some products contain arachis (peanut) oil, soya or soya derivative
Patients on long-term therapy should be regularly reviewed
Potential for drug abuse
Reassess need for continued treatment at regular intervals
Tolerance and dependence may occur
Excessive use may increase frequency of headache, may require withdrawal
Seek urgent medical advice in event of overdose, even if patient feels well
May affect results of some laboratory tests
Avoid abrupt withdrawal
Reduce dose in elderly
Avoid prolonged use
Advise patient not to take paracetamol during treatment
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise that alcohol increases the chances of liver damage with paracetamol
Advise that effects are potentiated by CNS depressants (including alcohol)
Advise patient to consult a doctor if symptoms persist despite treatment
Patients should not exceed recommended dose

Care should be observed in administering the product to any patient whose condition may be exacerbated by opioids.

A reduced dose is recommended, due to increased sensitivity to side effects in elderly or debilitated patients, in hypothyroidism, and in adrenocortical insufficiency.

Codeine should not be used in children under 18 years who are post operative or undergoing tonsillectomy and/or adenoidectomy for obstructive sleep apnoea due to life-threatening adverse events including death.

Codeine should not be used in children who have impaired respiratory function including neuromuscular disorders, severe cardiac or respiratory function, upper respiratory or lung infections, multiple trauma or extensive surgical procedures.

Codeine is metabolised by the liver enzyme CYP2D6 into morphine, its active metabolite. Patients with a deficiency or completely lacking this enzyme will not experience an adequate analgesic effect. 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.

Care should be observed if prolonged therapy is contemplated, and the risk-benefit of continued use should be assessed regularly. Symptoms of restlessness and irritability may result when treatment is then stopped.

The effects of CNS depressants (including alcohol) may be potentiated by codeine. Chronic heavy alcohol abusers may be at increased risk of liver toxicity from excessive paracetamol use, although reports of this event are rare. The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease.

Paracetamol should be recommended in low or moderate doses i.e. less than 1000mg in a single dose in patients who have experienced an asthmatic reaction to aspirin or non-steroidal anti-inflammatory drugs (NSAIDS) since cross reactions have been reported in patients with aspirin sensitivity.

Advise patients not to take other products containing paracetamol or opiate derivatives. Serious delayed liver damage is possible in adults who have taken 10g or more of paracetamol. Patients on long term treatment with drugs which induce liver enzymes, such as St. John's Wort, are at risk of liver damage from paracetamol doses of 5 grams or more.

Adverse reactions may be more prominent high doses and in ambulatory rather than non-ambulatory positions and thus may be alleviated by lying down.

Some effervescent formulations contain a significant amount of sodium. This should be taken into account when treating patients with restricted sodium intake.

Opioids may interfere with the results of plasma amylase, lipase, bilirubin, ALP, LDH, AST and ALT results. The effects of codeine on the gut may interfere with diagnostic tests of gastro intestinal functions.

Pregnancy and Lactation

Pregnancy

Careful consideration should be given before prescribing co-codamol for pregnant patients due to inadequate evidence for safety.

Paracetamol
Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol. Paracetamol is commonly used during all stages of pregnancy. There does not appear to be a risk to the embryo or foetus from the maternal use of therapeutic doses. Paracetamol crosses the placenta easily and does not inhibit prostaglandin synthesis.

Codeine
There is inadequate evidence of the safety of codeine in human pregnancy. Various reports have described associations between 1st trimester exposure to codeine and congenital defects. However, there is no clear evidence that opiates cause structural anomalies. Schaefer 2015, states that codeine may be used for analgesia if paracetamol alone is not sufficiently effective. Potential for dependency must also be kept in mind when prolonged treatment is required. Long term use during pregnancy may cause withdrawal syndromes in neonates and use during labour may cause neonatal respiratory depression.

Paracetamol and codeine have been used for many years without apparent ill consequences and animal studies have not shown any hazard.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Careful consideration should be given before prescribing co-codamol for lactating patients due to inadequate evidence for safety. Use is contraindicated by some manufacturers.

Paracetamol
The amount of paracetamol excreted in human milk is much less than the doses usually given to infants and adverse effects in infants are rarely observed. Paracetamol is the analgesic and antipyretic of choice during breastfeeding.

Codeine
Can cause infant drowsiness and a physician must be contacted immediately if any of the following symptoms are observed in the infant, such as more than usual sleepiness, limpness, difficulty feeding or breathing. The amount of codeine (and morphine) in the breast milk can vary widely depending on the metabolism through CYP2D6 by the mother. Ultra rapid metabolisers of CY2D6 may produce larger amounts of the active metabolite morphine and put the infant, and particularly neonates, at increased risk from adverse effects. There is a report of an infant fatality due to exposure from breast milk from an ultra fast metabolising mother. Therefore long-term consumption of codeine-containing products should be avoided during breastfeeding. Regular use of any opioid beyond 1 to 2 days should be under close medical supervision (Briggs 2015).

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Addiction
Agranulocytosis
Allergic reaction
Anaphylaxis
Angioedema
Anorexia
Blood dyscrasias
Bradycardia
Cerebral oedema
Confusion
Constipation
Deafness
Dependence
Difficulty in micturition
Dizziness
Drowsiness
Dry mouth
Dysphoria
Euphoria
Headache
Hypersensitivity reactions
Hypotension
Leucopenia
Light-headedness
Liver damage
Miosis
Mood changes
Muscle rigidity
Nausea
Neutropenia
Pancreatitis
Postural hypotension
Pruritus
Rash
Respiratory depression
Sedation
Sleep apnoea
Stevens-Johnson syndrome
Tachycardia
Thrombocytopenia
Tolerance
Toxic epidermal necrolysis
Urinary retention
Urticaria
Visual disturbances
Vomiting

Presentation

Oral formulations of high strength codeine and paracetamol (containing 15mg or more of codeine phosphate).

Drugs List

Therapeutic Indications

Uses

Pain - moderate to severe

Dosage

Dosage should be adjusted according to the severity of the pain and the response of the patient. Where possible, treatment duration should be limited to 3 days.

Adults

Children

Patients with Renal Impairment

Contraindications

Acute alcohol intoxication
Children under 12 years
Risk of paralytic ileus
Acute asthma
Acute diarrhoea
Acute ulcerative colitis
CYP2D6 ultra-rapid metaboliser genotype
Head trauma
Obstructive pulmonary disease
Paralytic ileus
Pseudomembranous enterocolitis
Raised intracranial pressure
Respiratory depression
Severe hepatic disorder

Precautions and Warnings

Abdominal pain of unknown cause
Elderly
Within 2 weeks of discontinuing MAOIs
Addison's disease
Adrenal insufficiency
Alcoholic liver disease
Asthma
Benign prostatic hyperplasia
Biliary tract disorder
Breastfeeding
Cardiac arrhythmias
Dehydration
Gastrointestinal obstruction
Hepatic impairment
Hereditary fructose intolerance
History of alcohol abuse
History of drug misuse
Hypotension
Hypothyroidism
Inflammatory bowel disease
Myasthenia gravis
Pregnancy
Renal impairment
Respiratory impairment
Urethral stricture

Children under 18 years: Increased risk of rare and severe adverse effects
Hepatic cirrhosis: hepatic coma may be precipitated
Reduce dose in patients with hepatic impairment
Sodium content of effervescent preparation may be significant
Advise patient ability to drive or operate machinery may be impaired
Advise patient dizziness may affect ability to drive or operate machinery
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine may be subject to driving restrictions
Avoid within 2 weeks of discontinuing a MAOI
Not all available strengths are licensed for all indications
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some brands contain metabisulfite, may cause bronchospasm/allergies
Some products contain arachis (peanut) oil, soya or soya derivative
Patients on long-term therapy should be regularly reviewed
Potential for drug abuse
Reassess need for continued treatment at regular intervals
Tolerance and dependence may occur
Excessive use may increase frequency of headache, may require withdrawal
Seek urgent medical advice in event of overdose, even if patient feels well
May affect results of some laboratory tests
Avoid abrupt withdrawal
Reduce dose in elderly
Avoid prolonged use
Advise patient not to take paracetamol during treatment
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise that alcohol increases the chances of liver damage with paracetamol
Advise that effects are potentiated by CNS depressants (including alcohol)
Advise patient to consult a doctor if symptoms persist despite treatment
Patients should not exceed recommended dose

Care should be observed in administering the product to any patient whose condition may be exacerbated by opioids.

A reduced dose is recommended, due to increased sensitivity to side effects in elderly or debilitated patients, in hypothyroidism, and in adrenocortical insufficiency.

Codeine should not be used in children under 18 years who are post operative or undergoing tonsillectomy and/or adenoidectomy for obstructive sleep apnoea due to life-threatening adverse events including death.

Codeine should not be used in children who have impaired respiratory function including neuromuscular disorders, severe cardiac or respiratory function, upper respiratory or lung infections, multiple trauma or extensive surgical procedures.

Codeine is metabolised by the liver enzyme CYP2D6 into morphine, its active metabolite. Patients with a deficiency or completely lacking this enzyme will not experience an adequate analgesic effect. 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.

Care should be observed if prolonged therapy is contemplated, and the risk-benefit of continued use should be assessed regularly. Symptoms of restlessness and irritability may result when treatment is then stopped.

The effects of CNS depressants (including alcohol) may be potentiated by codeine. Chronic heavy alcohol abusers may be at increased risk of liver toxicity from excessive paracetamol use, although reports of this event are rare. The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease.

Paracetamol should be recommended in low or moderate doses i.e. less than 1000mg in a single dose in patients who have experienced an asthmatic reaction to aspirin or non-steroidal anti-inflammatory drugs (NSAIDS) since cross reactions have been reported in patients with aspirin sensitivity.

Advise patients not to take other products containing paracetamol or opiate derivatives. Serious delayed liver damage is possible in adults who have taken 10g or more of paracetamol. Patients on long term treatment with drugs which induce liver enzymes, such as St. John's Wort, are at risk of liver damage from paracetamol doses of 5 grams or more.

Adverse reactions may be more prominent high doses and in ambulatory rather than non-ambulatory positions and thus may be alleviated by lying down.

Some effervescent formulations contain a significant amount of sodium. This should be taken into account when treating patients with restricted sodium intake.

Opioids may interfere with the results of plasma amylase, lipase, bilirubin, ALP, LDH, AST and ALT results. The effects of codeine on the gut may interfere with diagnostic tests of gastro intestinal functions.

Pregnancy and Lactation

Pregnancy

Careful consideration should be given before prescribing co-codamol for pregnant patients due to inadequate evidence for safety.

Paracetamol
Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol. Paracetamol is commonly used during all stages of pregnancy. There does not appear to be a risk to the embryo or foetus from the maternal use of therapeutic doses. Paracetamol crosses the placenta easily and does not inhibit prostaglandin synthesis.

Codeine
There is inadequate evidence of the safety of codeine in human pregnancy. Various reports have described associations between 1st trimester exposure to codeine and congenital defects. However, there is no clear evidence that opiates cause structural anomalies. Schaefer 2015, states that codeine may be used for analgesia if paracetamol alone is not sufficiently effective. Potential for dependency must also be kept in mind when prolonged treatment is required. Long term use during pregnancy may cause withdrawal syndromes in neonates and use during labour may cause neonatal respiratory depression.

Paracetamol and codeine have been used for many years without apparent ill consequences and animal studies have not shown any hazard.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Careful consideration should be given before prescribing co-codamol for lactating patients due to inadequate evidence for safety. Use is contraindicated by some manufacturers.

Paracetamol
The amount of paracetamol excreted in human milk is much less than the doses usually given to infants and adverse effects in infants are rarely observed. Paracetamol is the analgesic and antipyretic of choice during breastfeeding.

Codeine
Can cause infant drowsiness and a physician must be contacted immediately if any of the following symptoms are observed in the infant, such as more than usual sleepiness, limpness, difficulty feeding or breathing. The amount of codeine (and morphine) in the breast milk can vary widely depending on the metabolism through CYP2D6 by the mother. Ultra rapid metabolisers of CY2D6 may produce larger amounts of the active metabolite morphine and put the infant, and particularly neonates, at increased risk from adverse effects. There is a report of an infant fatality due to exposure from breast milk from an ultra fast metabolising mother. Therefore long-term consumption of codeine-containing products should be avoided during breastfeeding. Regular use of any opioid beyond 1 to 2 days should be under close medical supervision (Briggs 2015).

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Effects on Ability to Drive and Operate Machinery

This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988 (England and Wales). This medicine may be subject to police testing and has specified maximum blood levels for driving.

When prescribing this medicine:

Advise patient the medicine can affect cognitive function and is likely to affect ability to drive.

Advise patient not to drive until they know how the medicine affects them.

It is an offence to drive while under the influence of this medicine. However, a patient is not committing an offence (called 'statutory defence') if: 1. The medicine has been prescribed to treat a medical or dental problem and 2. The medicine has been taken according to the instructions given by the prescriber and/or in the information provided with the medicine, and 3. The medicine was not affecting the ability to drive safely. For further guidance see https://www.gov.uk

Side Effects

Abdominal pain
Addiction
Agranulocytosis
Allergic reaction
Anaphylaxis
Angioedema
Anorexia
Blood dyscrasias
Bradycardia
Cerebral oedema
Confusion
Constipation
Deafness
Dependence
Difficulty in micturition
Dizziness
Drowsiness
Dry mouth
Dysphoria
Euphoria
Headache
Hypersensitivity reactions
Hypotension
Leucopenia
Light-headedness
Liver damage
Miosis
Mood changes
Muscle rigidity
Nausea
Neutropenia
Pancreatitis
Postural hypotension
Pruritus
Rash
Respiratory depression
Sedation
Sleep apnoea
Stevens-Johnson syndrome
Tachycardia
Thrombocytopenia
Tolerance
Toxic epidermal necrolysis
Urinary retention
Urticaria
Visual disturbances
Vomiting

Effects on Laboratory Tests

Opioids may interfere with the results of plasma amylase, lipase, bilirubin, ALP, LDH, AST and ALT results.

The effects of codeine on the gut may interfere with diagnostic tests of gastro intestinal functions.

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Full Review Date: January 2018

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.

Summary of Product Characteristics: Co-codamol 60/1000mg Film-coated Tablets. Actavis UK LTD. Revised December 2016.
Summary of Product Characteristics: Co-codamol 30/500 Tablets, effervescent tablets, capsules. Winthrop Pharmaceuticals UK Ltd. Revised December 2016.
Summary of Product Characteristics: Copaz or Codipar caplet. Goldshield Pharmaceuticals Ltd. Revised April 2017.
Summary of Product Characteristics: Codipar effervescent tablet. Goldshield Pharmaceuticals Ltd. Revised April 2017.
Summary of Product Characteristics: Codipar capsules. Goldshield Pharmaceuticals Ltd. Revised April 2017.
Summary of Product Characteristics: Emcozin 30/500mg Tablets. M & A Pharmachem Ltd.
Summary of Product Characteristics: Solpadol Capsules, Solpadol Effervescent Tablets, Solpadol Caplets. Sanofi-Aventis. Revised December 2016.
Summary of Product Characteristics: Tylex effervescent. UCB Pharma Ltd. Revised May 2015.
Summary of Product Characteristics: Tylex capsules. UCB Pharma Ltd. Revised December 2015.
Summary of Product Characteristics: Kapake Tablets, Co-Codamol Tablets 30/500. Galen Ltd. Revised October 2017.
Summary of Product Characteristics: Kapake capsules, Co-Codamol Capsules 30/500. Galen Ltd. Revised October 2017.
Summary of Product Characteristics: Kapake Tablets, 15/500. Galen Ltd. Revised February 2011.
Summary of Product Characteristics: Zapain Capsules. Goldshield Pharmaceuticals Ltd. Revised April 2017.
Summary of Product Characteristics: Zapain Caplets. Goldshield Pharmaceuticals Ltd. Revised October 2010.
Summary of Product Characteristics: Co-codamol 30mg/500mg/5ml oral solution. Wockhardt UK Ltd. Revised June 2019.

Gov.uk. Government departments. Department for Transport. Publications. Drug driving and medicine: advice for healthcare professionals. Drug driving: Guidance for healthcare professionals on drug driving. Available at: https://www.gov.uk Last accessed: 02 January 2018

National electronic Library for Medicines. Can Breastfeeding mothers take codeine?
https://www.nelm.nhs.uk/en/NeLM-Area/Evidence/Medicines-Q--A/Can-breastfeeding-mothers-take-codeine/?query=+pain+breastfeeding&rank=100
Last revised: 10 September 2013
Last accessed: 02 January 2018

New drug driving offence: implications for medicines packaging. Medicines Regulatory News. 10 December 2013. Available at: https://www.mhra.gov.uk Last accessed: 02 January 2018

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 14/09/2018

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Acetaminophen (Paracetamol) Last revised: 11 April 2017
Last accessed: 20 December 2017

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Codeine Last revised: 05 September 2017
Last accessed: 20 December 2017