Drugs List

Therapeutic Indications

Uses

Pain - mild to moderate

Administration

For administration by intramuscular injection only.

Contraindications

Acute alcohol intoxication
Children under 12 years
Predisposition to paralytic ileus
Risk of paralytic ileus
Acute asthma
Acute respiratory depression
Breastfeeding
CYP2D6 ultra-rapid metaboliser genotype
Head trauma
Paralytic ileus
Phaeochromocytoma
Raised intracranial pressure
Severe hepatic impairment
Severe renal impairment

Precautions and Warnings

Acute abdomen
Debilitation
Elderly
Shock
Within 2 weeks of discontinuing MAOIs
Adrenal insufficiency
Asthma
Benign prostatic hyperplasia
Biliary tract disorder
Cardiac arrhythmias
Epileptic disorder
Hepatic impairment
History of drug misuse
Hypotension
Hypothyroidism
Inflammatory bowel disease
Myasthenia gravis
Pregnancy
Reduced respiratory reserve
Renal impairment
Seizures

Children under 18 years: Increased risk of rare and severe adverse effects
Reduce dose in hypothyroidism
Reduce dose in patients with hepatic impairment
Reduce dose in patients with renal impairment
Advise patient ability to drive or operate machinery may be impaired
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine may be subject to driving restrictions
Potential for drug abuse
Tolerance and dependence may occur
Avoid abrupt withdrawal
Maintain treatment at the lowest effective dose
Reduce dose in debilitated patients
Reduce dose in elderly
Avoid long term continuous therapy
Advise patient to avoid alcohol during treatment

The use of codeine is not recommended in children under 18 years of age as it has been associated with rare but serious adverse reactions. Younger children may be more susceptible and codeine should not be used in children under 12 years of age.

Codeine should not be used in children under 18 years who are undergoing the removal of tonsils due to an increased risk of severe breathing difficulties.

Pregnancy and Lactation

Pregnancy

Codeine should be used with caution in pregnancy.

There have been reports describing association between first trimester exposure to opioid analgesics and congenital defects such as respiratory malformation. When used in late pregnancy, there is a risk of neonatal withdrawal symptoms or respiratory depression. There is also evidence of foetal and newborn toxicity if the mother is addicted to codeine or opioids or consumes high doses of these agents during the latter half of pregnancy or close to delivery. In all cases evaluate whether the benefit to the mother out weighs the risk to the foetus.

Studies have been conducted in mice, rats, hamsters and rabbits. High subcutaneous doses ranging from 73 to 360 mg/kg in hamsters resulted in an incidence of 6% to 8% of cranioschisis. Codeine was not found to be teratogenic in rats or rabbits.

Codeine has been prescribed as a heroin substitute for patients suffering from drug addiction. Due to its addictive properties, codeine has be abused by pregnant women in the past and its administration to patients with a history of drug misuse or who may be currently receiving codeine as a heroin substitute should be deliberated.

Schaefer concludes that codeine may be used in all trimesters of pregnancy for dry coughs. Though the potential for dependency must always be kept in mind.

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

Codeine is contraindicated in breastfeeding.

The Lancet has described a case where a breastfed neonate died from morphine poisoning associated with maternal codeine used for episiotomy pain. It was found that the mother was an ultra-rapid codeine metaboliser as a result of CYP2D6 polymorphisms, which is expressed in 1to 2% of the UK population. All patients should be advised of the typical side-effects of opioids because most patients are not aware of their CYP2D6 status. If any symptoms of opioid toxicity develop in the mother or baby (e.g., nausea, vomiting, lack of appetite, and somnolence, with symptoms of circulatory and respiratory depression in severe cases) patients should stop taking all codeine containing products, and alternative medicines should be prescribed. In severe cases, naloxone may be appropriate to reverse the effects. European and UK regulatory bodies (EMA/MHRA) have contraindicated the use of codeine in breastfeeding mothers.

Neonate infants particularly in the first week of life can be sensitive to even small doses of narcotic analgesics which can cause infant drowsiness, asymptomatic bradycardia, apnoea or cyanosis and may contribute to neuroblastoma.

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
Anorexia
Biliary spasm
Bradycardia
Confusion
Constipation
Convulsions
Dependence
Difficulty in micturition
Dizziness
Drowsiness
Dry mouth
Dysphoria
Euphoria
Facial flushing
Fasciculation
Hallucinations
Headache
Hypotension
Hypothermia
Malaise
Miosis
Mood changes
Muscle rigidity
Nausea
Oedema
Palpitations
Pancreatitis
Postural hypotension
Pruritus
Rash
Reduced libido
Reduction of male potency
Respiratory depression
Sexual dysfunction
Sleep disturbances
Sweating
Tachycardia
Ureteric spasm
Urinary retention
Urticaria
Vertigo
Visual disturbances
Vomiting

Presentation

Solution for injection containing codeine phosphate

Drugs List

Therapeutic Indications

Uses

Pain - mild to moderate

Dosage

Adults

Elderly

Children

Administration

For administration by intramuscular injection only.

Contraindications

Acute alcohol intoxication
Children under 12 years
Predisposition to paralytic ileus
Risk of paralytic ileus
Acute asthma
Acute respiratory depression
Breastfeeding
CYP2D6 ultra-rapid metaboliser genotype
Head trauma
Paralytic ileus
Phaeochromocytoma
Raised intracranial pressure
Severe hepatic impairment
Severe renal impairment

Precautions and Warnings

Acute abdomen
Debilitation
Elderly
Shock
Within 2 weeks of discontinuing MAOIs
Adrenal insufficiency
Asthma
Benign prostatic hyperplasia
Biliary tract disorder
Cardiac arrhythmias
Epileptic disorder
Hepatic impairment
History of drug misuse
Hypotension
Hypothyroidism
Inflammatory bowel disease
Myasthenia gravis
Pregnancy
Reduced respiratory reserve
Renal impairment
Seizures

Children under 18 years: Increased risk of rare and severe adverse effects
Reduce dose in hypothyroidism
Reduce dose in patients with hepatic impairment
Reduce dose in patients with renal impairment
Advise patient ability to drive or operate machinery may be impaired
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine may be subject to driving restrictions
Potential for drug abuse
Tolerance and dependence may occur
Avoid abrupt withdrawal
Maintain treatment at the lowest effective dose
Reduce dose in debilitated patients
Reduce dose in elderly
Avoid long term continuous therapy
Advise patient to avoid alcohol during treatment

The use of codeine is not recommended in children under 18 years of age as it has been associated with rare but serious adverse reactions. Younger children may be more susceptible and codeine should not be used in children under 12 years of age.

Codeine should not be used in children under 18 years who are undergoing the removal of tonsils due to an increased risk of severe breathing difficulties.

Pregnancy and Lactation

Pregnancy

Codeine should be used with caution in pregnancy.

There have been reports describing association between first trimester exposure to opioid analgesics and congenital defects such as respiratory malformation. When used in late pregnancy, there is a risk of neonatal withdrawal symptoms or respiratory depression. There is also evidence of foetal and newborn toxicity if the mother is addicted to codeine or opioids or consumes high doses of these agents during the latter half of pregnancy or close to delivery. In all cases evaluate whether the benefit to the mother out weighs the risk to the foetus.

Studies have been conducted in mice, rats, hamsters and rabbits. High subcutaneous doses ranging from 73 to 360 mg/kg in hamsters resulted in an incidence of 6% to 8% of cranioschisis. Codeine was not found to be teratogenic in rats or rabbits.

Codeine has been prescribed as a heroin substitute for patients suffering from drug addiction. Due to its addictive properties, codeine has be abused by pregnant women in the past and its administration to patients with a history of drug misuse or who may be currently receiving codeine as a heroin substitute should be deliberated.

Schaefer concludes that codeine may be used in all trimesters of pregnancy for dry coughs. Though the potential for dependency must always be kept in mind.

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

Codeine is contraindicated in breastfeeding.

The Lancet has described a case where a breastfed neonate died from morphine poisoning associated with maternal codeine used for episiotomy pain. It was found that the mother was an ultra-rapid codeine metaboliser as a result of CYP2D6 polymorphisms, which is expressed in 1to 2% of the UK population. All patients should be advised of the typical side-effects of opioids because most patients are not aware of their CYP2D6 status. If any symptoms of opioid toxicity develop in the mother or baby (e.g., nausea, vomiting, lack of appetite, and somnolence, with symptoms of circulatory and respiratory depression in severe cases) patients should stop taking all codeine containing products, and alternative medicines should be prescribed. In severe cases, naloxone may be appropriate to reverse the effects. European and UK regulatory bodies (EMA/MHRA) have contraindicated the use of codeine in breastfeeding mothers.

Neonate infants particularly in the first week of life can be sensitive to even small doses of narcotic analgesics which can cause infant drowsiness, asymptomatic bradycardia, apnoea or cyanosis and may contribute to neuroblastoma.

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). 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.

Side Effects

Abdominal pain
Anorexia
Biliary spasm
Bradycardia
Confusion
Constipation
Convulsions
Dependence
Difficulty in micturition
Dizziness
Drowsiness
Dry mouth
Dysphoria
Euphoria
Facial flushing
Fasciculation
Hallucinations
Headache
Hypotension
Hypothermia
Malaise
Miosis
Mood changes
Muscle rigidity
Nausea
Oedema
Palpitations
Pancreatitis
Postural hypotension
Pruritus
Rash
Reduced libido
Reduction of male potency
Respiratory depression
Sexual dysfunction
Sleep disturbances
Sweating
Tachycardia
Ureteric spasm
Urinary retention
Urticaria
Vertigo
Visual disturbances
Vomiting

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 ).

Signs and Symptoms

Central nervous system depression, including respiratory depression, may develop but is unlikely to be severe unless other sedative agents have been co-ingested, including alcohol, or the overdose is very large. The pupils may be pin-point in size; nausea and vomiting are common. Hypotension and tachycardia are possible but unlikely.

Treatment

This should include general symptomatic and supportive measures including a clear airway and monitoring of vital signs until stable. Consider activated charcoal if an adult presents within one hour of ingestion of more than 350 mg or a child more than 5 mg/kg.

Give naloxone if coma or respiratory depression is present. Naloxone is a competitive antagonist and has a short half-life so large and repeated doses may be required in a seriously poisoned patient. Observe for at least four hours after ingestion, or eight hours if a sustained release preparation has been taken.

Further Information

Last Full Review Date: May 2016

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press Accessed on 09 May 2016.

Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.

Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications Accessed on 09 May 2016.

Summary of Product Characteristics: Codeine Phosphate BP injection. Martindale Pharmaceuticals. Revised December 2007

MHRA 22nd January 2007
https://webarchive.nationalarchives.gov.uk/20141205150130/https://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/Informationforlicenceapplicants/Guidance/OverdosesectionsofSPCs/Genericoverdosesections/Codeine/index.htm Last accessed: 09 May 2016

UK Drugs in Lactation Advisory Service.
Available at: https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Last accessed: 09 May 2016

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: 6 January 2015 New drug driving offence implications for medicines packaging. Medicines Regulatory News. 10 December 2013. Available at: https://www.mhra.gov.uk Last accessed: 6 January 2015