Drugs List

Therapeutic Indications

Uses

Pain - mild to moderate

Symptomatic relief of mild to moderate pain in such conditions as:
Soft tissue injuries
Sprains
Strains
Musculo-tendinous conditions
Backache
Non-serious arthritic and rheumatic conditions

Also for the relief of mild to moderate pain in:
Neuralgia
Migraine
Headache
Dental pain
Dysmenorrhoea

The MHRA advises that these products should only be used for the short term treatment of acute, moderate pain which is not relieved by paracetamol, ibuprofen or aspirin alone.

Contraindications

Children under 12 years
Risk of paralytic ileus
Acute asthma
Chronic constipation
Chronic obstructive pulmonary disease
Coma
CYP2D6 ultra-rapid metaboliser genotype
Head trauma
History of gastrointestinal haemorrhage secondary to NSAID
History of peptic ulcer
Peptic ulcer
Raised intracranial pressure
Severe cardiac failure
Severe hepatic impairment
Severe renal impairment
Third trimester of pregnancy

Precautions and Warnings

Acute abdomen
Debilitation
Elderly
Within 2 weeks of discontinuing MAOIs
Adrenal insufficiency
Asthma
Benign prostatic hyperplasia
Biliary tract disorder
Breastfeeding
Cardiac arrhythmias
Cardiac impairment
Cholecystectomy
Cholelithiasis
Connective tissue disorder
CYP2D6 poor metaboliser genotype
First trimester of pregnancy
Galactosaemia
Gastrointestinal disorder
Glucose-galactose malabsorption syndrome
Haematological disorder
Hepatic impairment
History of asthma
History of cardiac failure
History of drug misuse
History of gastrointestinal disorder
Hypertension
Hypotension
Hypothyroidism
Inflammatory bowel disease
Lactose intolerance
Myasthenia gravis
Renal impairment
Respiratory impairment
Second trimester of pregnancy
Seizures
Systemic lupus erythematosus

Children under 18 years: Increased risk of rare and severe adverse effects
May precipitate bronchospasm in patients with asthma or allergy
NSAIDs may provoke or exacerbate asthma
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
Determine CYP2D6 metaboliser status before initiation of treatment
Some formulations contain lactose
Can cause addiction
Discontinue if signs of gastro-intestinal bleeding occur
Monitor patients receiving concurrent anticoagulants
Monitor renal function in patients with renal impairment
Advise patient to report any abdominal or pelvic pain
Discontinue if signs of gastro-intestinal ulceration occur
Excessive use may increase frequency of headache, may require withdrawal
May cause dependence
Withdrawal symptoms after long-term normal use on abrupt cessation
Discontinue treatment if gastrointestinal perforation occurs
Discontinue treatment if skin rash or other allergic reaction occurs
Maintain treatment at the lowest effective dose
Reduce dose in elderly
For three days use only
May cause impaired fertility
Discontinue and consult a doctor if there is no improvement within 3 days

History of gastrointestinal toxicity, particularly in elderly patients - advise patients to report any unusual abdominal symptoms, particularly in initial stages of treatment.

Gastro-intestinal bleeding, ulceration or perforation, possibly fatal, have been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious gastrointestinal events. If gastro-intestinal bleeding or ulceration occurs, treatment should be withdrawn.

Anticoagulant therapy - prothrombin time should be monitored daily for the first few days of combined treatment.

Use with caution in patients with a history of hypertension and/or heart failure as fluid retention, hypertension and oedema have been reported in association with NSAID therapy.

Ultra-rapid metabolisers (CYP2D6 genotype), convert codeine into its active metabolite, morphine, more rapidly and completely than other people, resulting in higher than expected serum morphine levels. Even at labelled dosage regimens, overdose symptoms such as extreme sleepiness, confusion or shallow breathing can occur.

Codeine should not be used in children under 18 years who undergo tonsillectomy and/or adenoidectomy for obstructive sleep apnoea syndrome due to an increased risk of developing serious and life-threatening adverse reactions including death.

Use with caution in renal, hepatic or cardiac impairment. In patients with renal impairment, renal function should be monitored since it may deteriorate following the use of any NSAID.

Patients should be advised to consult their doctor if the medicine is needed for longer periods in higher doses than recommended, and if stopping the medicine makes them feel unwell but they feel better when they start taking it again.

May cause impairment of female fertility via an effect on ovulation, which is reversible upon withdrawal of treatment.

Use of ibuprofen may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke).

Serious and potential fatal skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported in association with the use of NSAIDs. Higher risk of these reactions appears to be early in the treatment, with the onset of the reaction occurring in the majority of cases within the first month of treatment. Ibuprofen and codeine should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Pregnancy and Lactation

Pregnancy

Ibuprofen and codeine is contraindicated during the third trimester of pregnancy but may be used with caution during the first and second trimester.

The manufacturer does not recommend using ibuprofen and codeine during pregnancy. Ibuprofen is contraindicated during the third trimester as there is a risk of premature closure of the foetal ductus arteriosus with possible persistent pulmonary hypertension. Labour onset may be delayed and its duration increased, with an increased bleeding tendency in both mother and child.

Codeine has been associated with neonatal respiratory depression and withdrawal. There is also the risk of gastric stasis and inhalation pneumonia in the mother during labour.

Lactation

Use ibuprofen and codeine with caution during breastfeeding.

The manufacturer does not recommend breastfeeding whilst taking ibuprofen and codeine. Both ibuprofen and codeine are secreted in breast milk at a very low concentration that is unlikely to adversely affect the breast fed infant.

Side Effects

Abdominal pain
Aggravation of existing asthma
Agranulocytosis
Allergic reaction
Alveolitis
Anaemia
Anaphylaxis
Angioedema
Anorexia
Aseptic meningitis
Asthma
Biliary spasm
Blood disorders
Bradycardia
Bronchospasm
Bullous reactions
Cardiac failure
Colitis
Confusion
Constipation
Cough suppression
Dependence
Depression
Diarrhoea
Dizziness
Drowsiness
Dry mouth
Dyspepsia
Dysphoria
Dyspnoea
Epidermal necrolysis
Erythema multiforme
Euphoria
Exacerbation of Crohn's disease
Facial oedema
Fasciculation
Flatulence
Flushing
Gastritis
Gastro-intestinal discomfort
Gastrointestinal bleeding
Haematemesis
Haematuria
Hallucinations
Headache
Hearing disturbances
Hepatic damage
Hepatic impairment
Hypersensitivity reactions
Hypertension
Hypotension
Hypothermia
Insomnia
Laryngeal swelling
Leucopenia
Malaise
Melaena
Micturition disorders
Miosis
Mood changes
Muscle rigidity
Nausea
Nervousness
Ocular changes
Oedema
Palpitations
Pancreatitis
Pancytopenia
Papillary necrosis
Peptic ulceration
Photosensitivity
Postural hypotension
Pruritus
Pulmonary eosinophilia
Purpura
Rash
Renal failure
Respiratory depression
Seizures
Sexual dysfunction
Shock
Sleep disturbances
Stevens-Johnson syndrome
Sweating
Tachycardia
Thrombocytopenia
Tinnitus
Tongue oedema
Toxic epidermal necrolysis
Ulcerative colitis
Ulcerative stomatitis
Ureteric spasm
Urinary retention
Urticaria
Vertigo
Visual disturbances
Vomiting
Withdrawal symptoms

Presentation

Oral formulations of ibuprofen and codeine phosphate.

Drugs List

Therapeutic Indications

Uses

Pain - mild to moderate

Symptomatic relief of mild to moderate pain in such conditions as:
Soft tissue injuries
Sprains
Strains
Musculo-tendinous conditions
Backache
Non-serious arthritic and rheumatic conditions

Also for the relief of mild to moderate pain in:
Neuralgia
Migraine
Headache
Dental pain
Dysmenorrhoea

The MHRA advises that these products should only be used for the short term treatment of acute, moderate pain which is not relieved by paracetamol, ibuprofen or aspirin alone.

Dosage

Advise patients not to take treatment for more than 3 days continuously without medical review.
The minimum effective dose should be used for the shortest time necessary to relieve symptoms.

Adults

Children

Contraindications

Children under 12 years
Risk of paralytic ileus
Acute asthma
Chronic constipation
Chronic obstructive pulmonary disease
Coma
CYP2D6 ultra-rapid metaboliser genotype
Head trauma
History of gastrointestinal haemorrhage secondary to NSAID
History of peptic ulcer
Peptic ulcer
Raised intracranial pressure
Severe cardiac failure
Severe hepatic impairment
Severe renal impairment
Third trimester of pregnancy

Precautions and Warnings

Acute abdomen
Debilitation
Elderly
Within 2 weeks of discontinuing MAOIs
Adrenal insufficiency
Asthma
Benign prostatic hyperplasia
Biliary tract disorder
Breastfeeding
Cardiac arrhythmias
Cardiac impairment
Cholecystectomy
Cholelithiasis
Connective tissue disorder
CYP2D6 poor metaboliser genotype
First trimester of pregnancy
Galactosaemia
Gastrointestinal disorder
Glucose-galactose malabsorption syndrome
Haematological disorder
Hepatic impairment
History of asthma
History of cardiac failure
History of drug misuse
History of gastrointestinal disorder
Hypertension
Hypotension
Hypothyroidism
Inflammatory bowel disease
Lactose intolerance
Myasthenia gravis
Renal impairment
Respiratory impairment
Second trimester of pregnancy
Seizures
Systemic lupus erythematosus

Children under 18 years: Increased risk of rare and severe adverse effects
May precipitate bronchospasm in patients with asthma or allergy
NSAIDs may provoke or exacerbate asthma
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
Determine CYP2D6 metaboliser status before initiation of treatment
Some formulations contain lactose
Can cause addiction
Discontinue if signs of gastro-intestinal bleeding occur
Monitor patients receiving concurrent anticoagulants
Monitor renal function in patients with renal impairment
Advise patient to report any abdominal or pelvic pain
Discontinue if signs of gastro-intestinal ulceration occur
Excessive use may increase frequency of headache, may require withdrawal
May cause dependence
Withdrawal symptoms after long-term normal use on abrupt cessation
Discontinue treatment if gastrointestinal perforation occurs
Discontinue treatment if skin rash or other allergic reaction occurs
Maintain treatment at the lowest effective dose
Reduce dose in elderly
For three days use only
May cause impaired fertility
Discontinue and consult a doctor if there is no improvement within 3 days

History of gastrointestinal toxicity, particularly in elderly patients - advise patients to report any unusual abdominal symptoms, particularly in initial stages of treatment.

Gastro-intestinal bleeding, ulceration or perforation, possibly fatal, have been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious gastrointestinal events. If gastro-intestinal bleeding or ulceration occurs, treatment should be withdrawn.

Anticoagulant therapy - prothrombin time should be monitored daily for the first few days of combined treatment.

Use with caution in patients with a history of hypertension and/or heart failure as fluid retention, hypertension and oedema have been reported in association with NSAID therapy.

Ultra-rapid metabolisers (CYP2D6 genotype), convert codeine into its active metabolite, morphine, more rapidly and completely than other people, resulting in higher than expected serum morphine levels. Even at labelled dosage regimens, overdose symptoms such as extreme sleepiness, confusion or shallow breathing can occur.

Codeine should not be used in children under 18 years who undergo tonsillectomy and/or adenoidectomy for obstructive sleep apnoea syndrome due to an increased risk of developing serious and life-threatening adverse reactions including death.

Use with caution in renal, hepatic or cardiac impairment. In patients with renal impairment, renal function should be monitored since it may deteriorate following the use of any NSAID.

Patients should be advised to consult their doctor if the medicine is needed for longer periods in higher doses than recommended, and if stopping the medicine makes them feel unwell but they feel better when they start taking it again.

May cause impairment of female fertility via an effect on ovulation, which is reversible upon withdrawal of treatment.

Use of ibuprofen may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke).

Serious and potential fatal skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported in association with the use of NSAIDs. Higher risk of these reactions appears to be early in the treatment, with the onset of the reaction occurring in the majority of cases within the first month of treatment. Ibuprofen and codeine should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Pregnancy and Lactation

Pregnancy

Ibuprofen and codeine is contraindicated during the third trimester of pregnancy but may be used with caution during the first and second trimester.

The manufacturer does not recommend using ibuprofen and codeine during pregnancy. Ibuprofen is contraindicated during the third trimester as there is a risk of premature closure of the foetal ductus arteriosus with possible persistent pulmonary hypertension. Labour onset may be delayed and its duration increased, with an increased bleeding tendency in both mother and child.

Codeine has been associated with neonatal respiratory depression and withdrawal. There is also the risk of gastric stasis and inhalation pneumonia in the mother during labour.

Lactation

Use ibuprofen and codeine with caution during breastfeeding.

The manufacturer does not recommend breastfeeding whilst taking ibuprofen and codeine. Both ibuprofen and codeine are secreted in breast milk at a very low concentration that is unlikely to adversely affect the breast fed infant.

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.

Counselling

Patients should be advised to consult their doctor if no relief from symptoms after 3 days.

Patients should be advised to use the lowest effective dose for the shortest duration necessary to control symptoms.

Patients should be advised not to drive or operate machinery if affected by dizziness or sedation.

Patients should be warned that taking codeine regularly for a long time can lead to addiction, and hence to feeling restless and irritable upon discontinuation.

Patients should be warned that taking a painkiller for headaches too often or for too long can make them worse.

Side Effects

Abdominal pain
Aggravation of existing asthma
Agranulocytosis
Allergic reaction
Alveolitis
Anaemia
Anaphylaxis
Angioedema
Anorexia
Aseptic meningitis
Asthma
Biliary spasm
Blood disorders
Bradycardia
Bronchospasm
Bullous reactions
Cardiac failure
Colitis
Confusion
Constipation
Cough suppression
Dependence
Depression
Diarrhoea
Dizziness
Drowsiness
Dry mouth
Dyspepsia
Dysphoria
Dyspnoea
Epidermal necrolysis
Erythema multiforme
Euphoria
Exacerbation of Crohn's disease
Facial oedema
Fasciculation
Flatulence
Flushing
Gastritis
Gastro-intestinal discomfort
Gastrointestinal bleeding
Haematemesis
Haematuria
Hallucinations
Headache
Hearing disturbances
Hepatic damage
Hepatic impairment
Hypersensitivity reactions
Hypertension
Hypotension
Hypothermia
Insomnia
Laryngeal swelling
Leucopenia
Malaise
Melaena
Micturition disorders
Miosis
Mood changes
Muscle rigidity
Nausea
Nervousness
Ocular changes
Oedema
Palpitations
Pancreatitis
Pancytopenia
Papillary necrosis
Peptic ulceration
Photosensitivity
Postural hypotension
Pruritus
Pulmonary eosinophilia
Purpura
Rash
Renal failure
Respiratory depression
Seizures
Sexual dysfunction
Shock
Sleep disturbances
Stevens-Johnson syndrome
Sweating
Tachycardia
Thrombocytopenia
Tinnitus
Tongue oedema
Toxic epidermal necrolysis
Ulcerative colitis
Ulcerative stomatitis
Ureteric spasm
Urinary retention
Urticaria
Vertigo
Visual disturbances
Vomiting
Withdrawal symptoms

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 for codeine :

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

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: August 2012

Reference Sources

Summary of Product Characteristics: Nurofen Plus. Reckitt Benckiser Healthcare (UK) Ltd. Revised January 2011.

Summary of Product Characteristics: Solpadeine Migraine Ibuprofen & Codeine tablets. Solpaflex. Cuprofen PLUS. Omega Pharma Ltd. Revised December 2015.

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: 18 September 2020

MHRA 22nd January 2007
https://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/Informationforlicenceapplicants/Guidance/OverdosesectionsofSPCs/Genericoverdosesections/index.htm
Last accessed: February 6, 2009

MHRA Drug Safety Update: Volume 3, Issue 2, September 2009. Over-the-counter painkillers containing codeine or dihydrocodeine.
https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON057141
Last accessed November 6, 2009

MHRA 2nd September 2009. Updated advice on non-prescription medicines containing codeine or dihydrocodeine (DHC).
https://www.mhra.gov.uk/SafetyInformation/Safetywarningsalertsandrecalls/Safetywarningsandmessagesformedicines/CON057118
Last accessed November 6, 2009

MHRA 16th October 2009. Guidance on the development of artwork in relation to medicines containing codeine and dihydrocodeine.
https://www.mhra.gov.uk/Howweregulate/Medicines/Medicinesregulatorynews/CON059982
Last accessed November 6, 2009
New drug driving offence: implications for medicines packaging. Medicines Regulatory News. 10 December 2013. Available at: https://www.mhra.gov.uk Last accessed: 18 September 2020.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 18 September 2020