Drugs List

Therapeutic Indications

Uses

Cough (dry or painful)
Diarrhoea - functional
Pain - mild to moderate

Contraindications

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

Precautions and Warnings

Acute abdomen
Children aged 12 to 18 years
Debilitation
Elderly
Shock
Within 2 weeks of discontinuing MAOIs
Adrenal insufficiency
Alcoholism
Asthma
Benign prostatic hyperplasia
Biliary tract disorder
Cardiac arrhythmias
Galactosaemia
Gall bladder disorder
Gastrointestinal obstruction
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of drug misuse
Hypotension
Hypothyroidism
Inflammatory bowel disease
Labour
Lactose intolerance
Myasthenia gravis
Opioid dependence
Phaeochromocytoma
Pregnancy
Recent gastrointestinal surgery
Recent surgery of the urinary tract
Reduced respiratory reserve
Renal impairment
Seizures
Urethral stricture

Children under 18 years: Increased risk of rare and severe adverse effects
Reduce dose in patients with hepatic impairment
Reduce dose in patients with renal impairment
Advise ability to drive/operate machinery may be affected by side effects
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
Not all available brands are licensed for all age groups
Some formulations contain lactose
Potential for drug abuse
Tolerance and dependence may occur
Advise patient to stop medication & contact GP if signs of opioid toxicity
Avoid abrupt withdrawal
Reduce dose in elderly
Avoid long term continuous therapy

Codeine use should be avoided in patients with infective diarrhoea as it may delay the passage of faeces and encourage proliferation of pathogens, consequently masking the severity of the condition.

Codeine should not be used in paediatric patients who are undergoing tonsillectomy and/or adenoidectomy for obstructive sleep apnoea syndrome due to the increased risk of adverse reactions.

Codeine is not recommended for use in children in whom respiratory function might be compromised (for example in 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.

The long term use of codeine phosphate should be assessed regularly, considering the risks and benefits.

Following recent urinary tract surgery, patients will be more prone to urinary retention caused by spasm of the urethral sphincter, and via constipation caused by codeine.

Patients with the CYP2D6 ultra-rapid metaboliser genotype may have an increased risk of developing side effects of opioid toxicity at commonly prescribed doses. These patients convert codeine into morphine rapidly resulting in higher than expected serum morphine levels.

Signs of opioid toxicity Patients, parents and caregivers who notice any of the following symptoms when taking, or in a patient given codeine, should stop the medicine and seek medical attention immediately: Slow or shallow breathing, confusion, sleepiness, small pupils, feeling or being sick, constipation and lack of appetite.

Pregnancy and Lactation

Pregnancy

Use codeine phosphate with caution in pregnancy. Codeine phosphate is contraindicated during labour.

The risks and benefits should be considered before administering codeine phosphate to a pregnant woman because opioid analgesics cross the placenta. Studies in animals have shown opioids to cause delayed ossification in mice and increased resorption in rats. Regular opioid use during pregnancy may cause physical dependence in the foetus, consequently leading to withdrawal symptoms in the neonate. Neonates exposed to codeine phosphate in pregnancy may experience respiratory malformations.

During labour, opioids enter the foetal circulation and may cause respiratory depression in the neonate. Gastric stasis and a risk of inhalation pneumonia could occur in the mother during labour. Administration should be avoided during the late stages of labour and during the delivery of a premature infant.
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 that foetal and newborn toxicity may occur 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 (Briggs, 2015).

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, 2007).

Schaefer (2007) concludes that codeine may be considered as an analgesic for pregnant women if paracetamol is not sufficiently effective. 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.

At normal therapeutic doses codeine phosphate (and its active metabolites) may be present in breast milk at very low doses and is unlikely to adversely affect the nursing infant. However, if the mother has a CYP2D6 ultra-rapid metaboliser genotype, higher levels of the active metabolite, morphine, may be present in breast milk. In very rare occasions, this may result in symptoms of opioid toxicity in the infant. If symptoms of opioid toxicity develop in either the mother or the infant, then all codeine containing medicines should be discontinued and replaced with non-opioid analgesics. In severe cases consideration should be given to prescribing naloxone to reverse these adverse effects.
LactMed suggests 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. Hale (2014), however, indicates that codeine taken in moderation for short durations is suitable for breastfeeding women and has limited adverse effects on their nursing infant. Hale (2014) continues, any report of overt somnolence, apnoea, poor feeding or grey skin should be reported immediately.

Briggs (2015) indicates that long term use of codeine phosphate should be avoided during breastfeeding, but short term therapy (1 to 2 days) may be compatible with close monitoring of the infant.

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
Anti-diuretic effect
Biliary spasm
Blurred vision
Bradycardia
Breathing difficulties
CNS excitation
Coma
Confusion
Constipation
Convulsions
Dependence
Depression
Difficulty in micturition
Dizziness
Double vision
Drowsiness
Dry mouth
Dysphoria
Erectile dysfunction
Euphoria
Excitement
Facial flushing
Faecal impaction
Fasciculation
Fever
Hallucinations
Headache
Hyperglycaemia
Hypotension
Hypothermia
Lymphadenopathy
Maculopapular rash
Malaise
Miosis
Mood changes
Muscle rigidity
Nausea
Nightmares
Oedema
Orthostatic hypotension
Palpitations
Pancreatitis
Postural hypotension
Pruritus
Raised intracranial pressure
Rash
Reduced libido
Reduction of male potency
Respiratory depression
Restlessness
Seizures
Sexual dysfunction
Sleep disturbances
Slight redness of the skin
Splenomegaly
Sweating
Tachycardia
Tiredness
Tolerance
Ureteric spasm
Urinary retention
Urticaria
Vertigo
Visual disturbances
Vomiting

Presentation

Oral formulations of codeine phosphate.

Drugs List

Therapeutic Indications

Uses

Cough (dry or painful)
Diarrhoea - functional
Pain - mild to moderate

Dosage

Administer the lowest effective dose over the shortest period of time.

The duration of treatment should be limited to 3 days.

Adults

Elderly

Children

Patients with Renal Impairment

Contraindications

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

Precautions and Warnings

Acute abdomen
Children aged 12 to 18 years
Debilitation
Elderly
Shock
Within 2 weeks of discontinuing MAOIs
Adrenal insufficiency
Alcoholism
Asthma
Benign prostatic hyperplasia
Biliary tract disorder
Cardiac arrhythmias
Galactosaemia
Gall bladder disorder
Gastrointestinal obstruction
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of drug misuse
Hypotension
Hypothyroidism
Inflammatory bowel disease
Labour
Lactose intolerance
Myasthenia gravis
Opioid dependence
Phaeochromocytoma
Pregnancy
Recent gastrointestinal surgery
Recent surgery of the urinary tract
Reduced respiratory reserve
Renal impairment
Seizures
Urethral stricture

Children under 18 years: Increased risk of rare and severe adverse effects
Reduce dose in patients with hepatic impairment
Reduce dose in patients with renal impairment
Advise ability to drive/operate machinery may be affected by side effects
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
Not all available brands are licensed for all age groups
Some formulations contain lactose
Potential for drug abuse
Tolerance and dependence may occur
Advise patient to stop medication & contact GP if signs of opioid toxicity
Avoid abrupt withdrawal
Reduce dose in elderly
Avoid long term continuous therapy

Codeine use should be avoided in patients with infective diarrhoea as it may delay the passage of faeces and encourage proliferation of pathogens, consequently masking the severity of the condition.

Codeine should not be used in paediatric patients who are undergoing tonsillectomy and/or adenoidectomy for obstructive sleep apnoea syndrome due to the increased risk of adverse reactions.

Codeine is not recommended for use in children in whom respiratory function might be compromised (for example in 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.

The long term use of codeine phosphate should be assessed regularly, considering the risks and benefits.

Following recent urinary tract surgery, patients will be more prone to urinary retention caused by spasm of the urethral sphincter, and via constipation caused by codeine.

Patients with the CYP2D6 ultra-rapid metaboliser genotype may have an increased risk of developing side effects of opioid toxicity at commonly prescribed doses. These patients convert codeine into morphine rapidly resulting in higher than expected serum morphine levels.

Signs of opioid toxicity Patients, parents and caregivers who notice any of the following symptoms when taking, or in a patient given codeine, should stop the medicine and seek medical attention immediately: Slow or shallow breathing, confusion, sleepiness, small pupils, feeling or being sick, constipation and lack of appetite.

Pregnancy and Lactation

Pregnancy

Use codeine phosphate with caution in pregnancy. Codeine phosphate is contraindicated during labour.

The risks and benefits should be considered before administering codeine phosphate to a pregnant woman because opioid analgesics cross the placenta. Studies in animals have shown opioids to cause delayed ossification in mice and increased resorption in rats. Regular opioid use during pregnancy may cause physical dependence in the foetus, consequently leading to withdrawal symptoms in the neonate. Neonates exposed to codeine phosphate in pregnancy may experience respiratory malformations.

During labour, opioids enter the foetal circulation and may cause respiratory depression in the neonate. Gastric stasis and a risk of inhalation pneumonia could occur in the mother during labour. Administration should be avoided during the late stages of labour and during the delivery of a premature infant.
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 that foetal and newborn toxicity may occur 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 (Briggs, 2015).

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, 2007).

Schaefer (2007) concludes that codeine may be considered as an analgesic for pregnant women if paracetamol is not sufficiently effective. 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.

At normal therapeutic doses codeine phosphate (and its active metabolites) may be present in breast milk at very low doses and is unlikely to adversely affect the nursing infant. However, if the mother has a CYP2D6 ultra-rapid metaboliser genotype, higher levels of the active metabolite, morphine, may be present in breast milk. In very rare occasions, this may result in symptoms of opioid toxicity in the infant. If symptoms of opioid toxicity develop in either the mother or the infant, then all codeine containing medicines should be discontinued and replaced with non-opioid analgesics. In severe cases consideration should be given to prescribing naloxone to reverse these adverse effects.
LactMed suggests 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. Hale (2014), however, indicates that codeine taken in moderation for short durations is suitable for breastfeeding women and has limited adverse effects on their nursing infant. Hale (2014) continues, any report of overt somnolence, apnoea, poor feeding or grey skin should be reported immediately.

Briggs (2015) indicates that long term use of codeine phosphate should be avoided during breastfeeding, but short term therapy (1 to 2 days) may be compatible with close monitoring of the infant.

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.

Side Effects

Abdominal pain
Anorexia
Anti-diuretic effect
Biliary spasm
Blurred vision
Bradycardia
Breathing difficulties
CNS excitation
Coma
Confusion
Constipation
Convulsions
Dependence
Depression
Difficulty in micturition
Dizziness
Double vision
Drowsiness
Dry mouth
Dysphoria
Erectile dysfunction
Euphoria
Excitement
Facial flushing
Faecal impaction
Fasciculation
Fever
Hallucinations
Headache
Hyperglycaemia
Hypotension
Hypothermia
Lymphadenopathy
Maculopapular rash
Malaise
Miosis
Mood changes
Muscle rigidity
Nausea
Nightmares
Oedema
Orthostatic hypotension
Palpitations
Pancreatitis
Postural hypotension
Pruritus
Raised intracranial pressure
Rash
Reduced libido
Reduction of male potency
Respiratory depression
Restlessness
Seizures
Sexual dysfunction
Sleep disturbances
Slight redness of the skin
Splenomegaly
Sweating
Tachycardia
Tiredness
Tolerance
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 ).

The MHRA have produced 'generic' overdose sections for the top ten drugs for which the NPIS received the greatest number of queries about management of overdose in 2002. This information is attached below:

The effects in overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs.

Further Information

Last Full Review: November 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, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

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

Summary of Product Characteristics: Codeine Phosphate Tablets 15mg . Actavis UK Ltd. Revised October 2016.
Summary of Product Characteristics: Codeine Phosphate Tablets 30mg. Actavis UK Ltd. Revised October 2016.
Summary of Product Characteristics: Codeine Phosphate Tablets 60mg. Actavis UK Ltd. Revised October 2016.

Summary of Product Characteristics: Codeine Phosphate 15mg Tablets. Wockhardt UK Ltd. Revised April 2017.
Summary of Product Characteristics: Codeine Phosphate 30mg Tablets. Wockhardt UK Ltd. Revised April 2017.
Summary of Product Characteristics: Codeine Phosphate 60mg Tablets. Wockhardt UK Ltd. Revised April 2017.

New drug driving offence implications for medicines packaging. Medicines Regulatory News. 10 December 2013. Available at: https://www.mhra.gov.uk Last accessed: 22 September 2016.

NICE - Evidence Services
Available at: www.nice.org.uk
Last accessed: 23 June 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: 04 February 2016
Last accessed: 22 September 2016.