Drugs List

Therapeutic Indications

Uses

Moderate pain: acute treatment

Short term treatment of acute, moderate pain which is not relieved by paracetamol, ibuprofen or aspirin alone.

Contraindications

Acute alcohol intoxication
Children under 12 years
Risk of paralytic ileus
Acute asthma
Breastfeeding
Chronic obstructive pulmonary disease
Coma
CYP2D6 ultra-rapid metaboliser genotype
Head trauma
Raised intracranial pressure
Respiratory depression

Precautions and Warnings

Acute abdomen
Debilitation
Elderly
Restricted sodium intake
Within 2 weeks of discontinuing MAOIs
Adrenal insufficiency
Alcoholism
Asthma
Benign prostatic hyperplasia
Biliary tract disorder
Cardiac arrhythmias
Cardiogenic shock
Cholecystectomy
Cholelithiasis
CYP2D6 poor metaboliser genotype
Gall bladder disorder
Gastrointestinal obstruction
Hepatic impairment
Hereditary fructose intolerance
History of drug misuse
Hypotension
Hypothyroidism
Inflammatory bowel disease
Myasthenia gravis
Non-cirrhotic alcoholic liver disease
Phenylketonuria
Pregnancy
Renal impairment
Respiratory impairment
Seizures

Children under 18 years: Increased risk of rare and severe adverse effects
Sodium content of effervescent preparation may be significant
Some formulations contain aspartame - caution in phenylketonuria
Advise ability to drive/operate machinery may be affected by side effects
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 indications
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Can cause addiction
Tolerance and dependence may occur
Excessive use may increase frequency of headache, may require withdrawal
Overdosage causes liver damage
Seek urgent medical advice in event of overdose, even if patient feels well
Withdraw gradually after long-term use
Avoid prolonged use
For three days use only
Avoid excessive intake of tea, coffee or other stimulants
Consult doctor if symptoms persist or treatment is required for > 3 days
Patients should not exceed recommended dose

Products containing codeine must not be used in children under 18 years who are undergoing the removal of tonsils or adenoids for obstructive sleep apnoea syndrome due to an increased risk of life-threatening adverse events including death.

Products containing codeine are not recommended in children whose breathing may be compromised (including neuromuscular disorders, severe cardiac or respiratory conditions, respiratory infections, multiple trauma or extensive surgical procedures). These factors may worsen symptoms of opiate toxicity.

Pregnancy and Lactation

Pregnancy

Use paracetamol with codeine and caffeine with caution during pregnancy.

The manufacturer recommends that paracetamol with codeine and caffeine should be avoided during pregnancy.

Paracetamol is the analgesic of choice during pregnancy. It crosses the placenta, but in therapeutic doses appears safe for short term use. Prolonged exposure should be avoided. Caffeine crosses the placenta with foetal blood and tissue levels that are similar to maternal concentrations. When used in moderation, no association with congenital malformations, spontaneous abortions, preterm birth and low birth weight has been proven.

Codeine crosses the placenta along with it's active metabolites (which includes morphine). Human data is limited but animal studies have not shown any hazard. Codeine has been linked to congenital defects including respiratory malformations following first trimester exposure. Codeine has been suggested as an option for short term use where paracetamol alone is ineffective. Use during the later stages of pregnancy does pose a risk of respiratory depression and withdrawal symptoms so any use during this period should be at low doses for short periods. As such, the largest risk of using the combined preparations lies with the codeine component. The quantity of codeine contained within available preparations is small so with short term use (3 days) the risk is likely to be low. Additional caution should be exercised during the first and third trimester. Maternal tolerability should also be monitored as CYP2D6 ultra-rapid metabolisers could experience higher levels of active metabolites of codeine and consequently higher levels of foetal exposure.

Lactation

Paracetamol with codeine and caffeine is contraindicated during breastfeeding.

Use of paracetamol with codeine and caffeine is contraindicated by the manufacturer.

At the time of writing there is limited published information regarding the use of paracetamol with codeine and caffeine during breastfeeding.

Paracetamol passes into the breast milk but exposure is well tolerated (Lactmed, 2018).

Data on individual components describes potential risks with exposure to codeine. Codeine itself is generally well tolerated but reports of CNS depression (including lethargy, apnoea and death) have raised concerns. In some of these cases, mothers have been identified as CYP2D6 ultra-rapid metabolisers. This condition results in higher maternal levels of active metabolites (including morphine) which pass into the breast milk and increase the infant's exposure. Following these reports, in 2013 the MHRA issued an alert advising against the use of codeine during breastfeeding.

Caffeine passes into the breast milk in variable amounts but exposure at normal doses (up to 300mg) is well tolerated. Accumulation of caffeine can develop in exposed preterm or newborn infants due to immature hepatic metabolism pathways requiring additional caution. High caffeine exposure causes irritability, restlessness and disturbed sleep patterns.

Side Effects

Abdominal pain
Addiction
Agranulocytosis
Allergic reaction
Anaphylaxis
Angioedema
Anorexia
Anxiety
Biliary spasm
Blood dyscrasias
Blurred vision
Bradycardia
Bronchospasm
Confusion
Constipation
Dependence
Difficulty in micturition
Dizziness
Double vision
Drowsiness
Dry mouth
Dyspepsia
Dysphoria
Dysuria
Euphoria
Facial flushing
Facial oedema
Fixed drug eruption
Fluid and electrolyte disturbances
Gastro-intestinal symptoms
Hallucinations
Headache
Hepatic damage
Hyperglycaemia
Hypersensitivity reactions
Hypoglycaemia
Hypotension
Hypothermia
Insomnia
Irritability
Leucopenia
Light-headedness
Malaise
Miosis
Mood changes
Muscle rigidity
Muscle twitch
Nausea
Nervousness
Neutropenia
Nightmares
Oedema
Palpitations
Pancreatitis
Polyuria
Postural hypotension
Pruritus
Rash
Reduced libido
Reduction of male potency
Renal damage
Respiratory depression
Restlessness
Seizures
Sexual dysfunction
Sleeplessness
Stevens-Johnson syndrome
Stomach pain
Sweating
Tachycardia
Thrombocytopenia
Tolerance
Toxic epidermal necrolysis
Tremor
Ureteric spasm
Urinary retention
Urticaria
Vertigo
Vomiting

Presentation

Oral formulations containing paracetamol, codeine phosphate and caffeine.

Drugs List

Therapeutic Indications

Uses

Moderate pain: acute treatment

Short term treatment of acute, moderate pain which is not relieved by paracetamol, ibuprofen or aspirin alone.

Dosage

The quantity of paracetamol, codeine and/or caffeine in each tablet/capsule/effervescent tablet is not consistent for all brands.
The recommended dose schedule remains the same for all products. As such, switching between different brands may cause changes in analgesic effect and/or the occurrence side effects. Where this cannot be avoided, adjust the dose according to response.

Adults

Children

Contraindications

Acute alcohol intoxication
Children under 12 years
Risk of paralytic ileus
Acute asthma
Breastfeeding
Chronic obstructive pulmonary disease
Coma
CYP2D6 ultra-rapid metaboliser genotype
Head trauma
Raised intracranial pressure
Respiratory depression

Precautions and Warnings

Acute abdomen
Debilitation
Elderly
Restricted sodium intake
Within 2 weeks of discontinuing MAOIs
Adrenal insufficiency
Alcoholism
Asthma
Benign prostatic hyperplasia
Biliary tract disorder
Cardiac arrhythmias
Cardiogenic shock
Cholecystectomy
Cholelithiasis
CYP2D6 poor metaboliser genotype
Gall bladder disorder
Gastrointestinal obstruction
Hepatic impairment
Hereditary fructose intolerance
History of drug misuse
Hypotension
Hypothyroidism
Inflammatory bowel disease
Myasthenia gravis
Non-cirrhotic alcoholic liver disease
Phenylketonuria
Pregnancy
Renal impairment
Respiratory impairment
Seizures

Children under 18 years: Increased risk of rare and severe adverse effects
Sodium content of effervescent preparation may be significant
Some formulations contain aspartame - caution in phenylketonuria
Advise ability to drive/operate machinery may be affected by side effects
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 indications
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Can cause addiction
Tolerance and dependence may occur
Excessive use may increase frequency of headache, may require withdrawal
Overdosage causes liver damage
Seek urgent medical advice in event of overdose, even if patient feels well
Withdraw gradually after long-term use
Avoid prolonged use
For three days use only
Avoid excessive intake of tea, coffee or other stimulants
Consult doctor if symptoms persist or treatment is required for > 3 days
Patients should not exceed recommended dose

Products containing codeine must not be used in children under 18 years who are undergoing the removal of tonsils or adenoids for obstructive sleep apnoea syndrome due to an increased risk of life-threatening adverse events including death.

Products containing codeine are not recommended in children whose breathing may be compromised (including neuromuscular disorders, severe cardiac or respiratory conditions, respiratory infections, multiple trauma or extensive surgical procedures). These factors may worsen symptoms of opiate toxicity.

Pregnancy and Lactation

Pregnancy

Use paracetamol with codeine and caffeine with caution during pregnancy.

The manufacturer recommends that paracetamol with codeine and caffeine should be avoided during pregnancy.

Paracetamol is the analgesic of choice during pregnancy. It crosses the placenta, but in therapeutic doses appears safe for short term use. Prolonged exposure should be avoided. Caffeine crosses the placenta with foetal blood and tissue levels that are similar to maternal concentrations. When used in moderation, no association with congenital malformations, spontaneous abortions, preterm birth and low birth weight has been proven.

Codeine crosses the placenta along with it's active metabolites (which includes morphine). Human data is limited but animal studies have not shown any hazard. Codeine has been linked to congenital defects including respiratory malformations following first trimester exposure. Codeine has been suggested as an option for short term use where paracetamol alone is ineffective. Use during the later stages of pregnancy does pose a risk of respiratory depression and withdrawal symptoms so any use during this period should be at low doses for short periods. As such, the largest risk of using the combined preparations lies with the codeine component. The quantity of codeine contained within available preparations is small so with short term use (3 days) the risk is likely to be low. Additional caution should be exercised during the first and third trimester. Maternal tolerability should also be monitored as CYP2D6 ultra-rapid metabolisers could experience higher levels of active metabolites of codeine and consequently higher levels of foetal exposure.

Lactation

Paracetamol with codeine and caffeine is contraindicated during breastfeeding.

Use of paracetamol with codeine and caffeine is contraindicated by the manufacturer.

At the time of writing there is limited published information regarding the use of paracetamol with codeine and caffeine during breastfeeding.

Paracetamol passes into the breast milk but exposure is well tolerated (Lactmed, 2018).

Data on individual components describes potential risks with exposure to codeine. Codeine itself is generally well tolerated but reports of CNS depression (including lethargy, apnoea and death) have raised concerns. In some of these cases, mothers have been identified as CYP2D6 ultra-rapid metabolisers. This condition results in higher maternal levels of active metabolites (including morphine) which pass into the breast milk and increase the infant's exposure. Following these reports, in 2013 the MHRA issued an alert advising against the use of codeine during breastfeeding.

Caffeine passes into the breast milk in variable amounts but exposure at normal doses (up to 300mg) is well tolerated. Accumulation of caffeine can develop in exposed preterm or newborn infants due to immature hepatic metabolism pathways requiring additional caution. High caffeine exposure causes irritability, restlessness and disturbed sleep patterns.

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
Addiction
Agranulocytosis
Allergic reaction
Anaphylaxis
Angioedema
Anorexia
Anxiety
Biliary spasm
Blood dyscrasias
Blurred vision
Bradycardia
Bronchospasm
Confusion
Constipation
Dependence
Difficulty in micturition
Dizziness
Double vision
Drowsiness
Dry mouth
Dyspepsia
Dysphoria
Dysuria
Euphoria
Facial flushing
Facial oedema
Fixed drug eruption
Fluid and electrolyte disturbances
Gastro-intestinal symptoms
Hallucinations
Headache
Hepatic damage
Hyperglycaemia
Hypersensitivity reactions
Hypoglycaemia
Hypotension
Hypothermia
Insomnia
Irritability
Leucopenia
Light-headedness
Malaise
Miosis
Mood changes
Muscle rigidity
Muscle twitch
Nausea
Nervousness
Neutropenia
Nightmares
Oedema
Palpitations
Pancreatitis
Polyuria
Postural hypotension
Pruritus
Rash
Reduced libido
Reduction of male potency
Renal damage
Respiratory depression
Restlessness
Seizures
Sexual dysfunction
Sleeplessness
Stevens-Johnson syndrome
Stomach pain
Sweating
Tachycardia
Thrombocytopenia
Tolerance
Toxic epidermal necrolysis
Tremor
Ureteric spasm
Urinary retention
Urticaria
Vertigo
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 ).

Further Information

Last Full Review Date: July 2020.

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.

Summary of Product Characteristics: Codasolve 8mg/500mg/30mg Effervescent Tablets. Kent Pharma UK Limited. Revised June 2020.
Summary of Product Characteristics: Solpadeine Plus soluble tablets. Omega Pharma Ltd. Revised December 2016.
Summary of Product Characteristics: Solpadeine Plus tablets. Omega Pharma Ltd. Revised July 2018.
Summary of Product Characteristics: Solpadeine Plus capsules. Omega Pharma Ltd. Revised January 2017.
Summary of Product Characteristics: Solpadeine Max Soluble Tablets. Omega Pharma Ltd. Revised December 2016.
Summary of Product Characteristics: Syndol Headache Relief Tablets. Zebtiva. Revised February 2017.
Summary of Product Characteristics: Ultramol soluble tablets. Sanofi. Revised May 2020.
Summary of Product Characteristics: Veganin caplets. Omega Pharma Ltd. Revised July 2018.

EMA 28th June 2013. Restrictions on the use of codeine for pain relief in children - CMDh endorses PRAC recommendation.
https://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Codeine_containing_medicinal_products/Position_provided_by_CMDh/WC500144850.pdf
Last accessed: 03 November 2017.
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: 15 June 2020.

MHRA 2nd September 2009. Updated advice on non-prescription medicines containing codeine or dihydrocodeine (DHC).
https://webarchive.nationalarchives.gov.uk/20141205203719/https://www.mhra.gov.uk/Safetyinformation/Safetywarningsalertsandrecalls/Safetywarningsandmessagesformedicines/CON057118
Archived site - content added on 05 December 2014.
Last accessed: 03 November 2017.

NICE Evidence Services. Available at: www.nice.org.uk Last accessed: 15 June 2020.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922
Acetaminophen. Last revised: 31 October 2018.
Caffeine. Last revised: 30 June 2019.
Codeine. Last revised: 15 June 2020.
Last accessed: 29 July 2020.