Drugs List

Therapeutic Indications

Uses

Pain - mild to moderate

Contraindications

Children under 16 years
Chronic dyspepsia
Coagulopathy
CYP2D6 ultra-rapid metaboliser genotype
Haemophilia
History of peptic ulcer
Nasal polyps associated with bronchospasm and NSAIDs
Obstructive pulmonary disease
Peptic ulcer
Pseudomembranous enterocolitis
Respiratory depression
Severe hepatic impairment
Severe renal impairment
Third trimester of pregnancy
Thrombocytopenia

Precautions and Warnings

Allergic disposition
Surgery
Within 2 weeks of discontinuing MAOIs
Adrenal insufficiency
Anaemia
Asthma
Breastfeeding
Bronchospasm
Cardiac failure
Cholelithiasis
Connective tissue disorder
CYP2D6 poor metaboliser genotype
Dehydration
Epileptic disorder
G6PD deficiency
Gall bladder disorder
Gastric mucosa lesion
Gout
Head trauma
Hepatic impairment
History of alcohol abuse
History of bronchospasm
History of drug misuse
Hypotension
Hypothyroidism
Inflammatory bowel disease
Myasthenia gravis
Phaeochromocytoma
Pregnancy
Prostate disorder
Raised intracranial pressure
Renal impairment
Systemic lupus erythematosus
Thyrotoxicosis
Uncontrolled hypertension

Children under 18 years: Increased risk of rare and severe adverse effects
NSAIDs may provoke or exacerbate asthma
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 not to drive until they know how the medicine affects them
Advise patient this medicine may be subject to driving restrictions
Can cause addiction
Discontinue if signs of gastro-intestinal bleeding occur
Risk of gastrointestinal haemorrhage
Discontinue if signs of gastro-intestinal ulceration occur
Excessive use may increase frequency of headache, may require withdrawal
May cause convulsions
May precipitate acute rhinitis
NSAIDs may provoke bronchospasm/urticaria in susceptible patients
May affect results of some laboratory tests
Discuss discontinuation prior to surgery
Discontinue if hypersensitivity reactions occur
Discontinue if patient is attempting to conceive
Avoid long term continuous therapy
For three days use only
Advise patient against the use of opioids during treatment
Advise patient to consult a doctor if symptoms persist despite treatment

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.

Aspirin should not be given to children under 16, unless specifically on the advice of a doctor.

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

Co-codaprin is contraindicated during the third trimester of pregnancy and is cautioned throughout the rest of pregnancy.

Salicylates, such as aspirin, should only be used during pregnancy when the potential benefits justify the possible risks to the foetus. Teratogenic effects have not been observed in humans but animal studies have shown salicylates can cause birth defects including fissure of the spine and skull, facial clefts and malformations of the CNS, viscera and skeleton. Aspirin should be avoided during the last 3 months of pregnancy because it may cause premature closure of the ductus arteriosus, prolong labour, delay birth and contribute to neonatal and maternal bleeding. Maternal ingestion of aspirin during the last two weeks of pregnancy may increase the risk of foetal or neonatal haemorrhage and should therefore be avoided.

Opioids such as codeine cross the placenta, and animal studies have shown delayed ossification in mice and increased resorption in rats. Regular use during pregnancy may cause foetal physical dependence, leading to neonatal withdrawal. Opioids enter foetal circulation during labour and may cause respiratory depression in the neonate. They should therefore be avoided during the late stages of labour and during the delivery of a premature infant.

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

Co-codaprin is cautioned during breastfeeding.

Patients who are breast feeding should not take aspirin as it is excreted in breast milk. Neonates excrete salicylates slowly and are more sensitive to the platelet inhibitory effect of aspirin in addition to the possible risk of Reye's Syndrome.

Codeine is distributed in breast milk in small amounts and therefore it is advisable to avoid administration of opioids in breastfeeding women. If opioid toxicity develops then co-codaprin should be stopped and in severe cases naloxone should be prescribed to reverse the effects.

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

Addiction
Allergic reaction
Anaemia
Angioneurotic oedema
Anti-diuretic effect
Aplastic anaemia
Asthma
Biliary spasm
Blurred vision
Bradycardia
Breathing difficulties
Bronchospasm
CNS excitation
Confusion
Constipation
Convulsions
Deafness
Decreased appetite
Dependence
Depression
Dizziness
Double vision
Drowsiness
Dry mouth
Flushing
Gastric irritation
Gastro-intestinal ulceration
Gastrointestinal bleeding
Haemolytic anaemia
Hallucinations
Headache
Heartburn
Hepatitis
Hypersensitivity reactions
Hypertension
Hypoprothrombinaemia
Hypotension
Hypothermia
Increased sweating
Malaise
Miosis
Mood changes
Nausea
Nightmares
Palpitations
Pancytopenia
Paralytic ileus
Raised intracranial pressure
Rash
Respiratory rate disturbances
Rhinitis
Salicylism
Sleep disturbances
Stomach pain
Tachycardia
Thrombocytopenia
Tinnitus
Tiredness
Tolerance
Toxic megacolon
Trembling
Tremor
Urate kidney stones
Ureteric spasm
Urticaria
Vertigo
Vomiting
Weakness

Presentation

Dispersible tablets containing aspirin and codeine phosphate

Drugs List

Therapeutic Indications

Uses

Pain - mild to moderate

Dosage

Adults

Elderly

Children

Contraindications

Children under 16 years
Chronic dyspepsia
Coagulopathy
CYP2D6 ultra-rapid metaboliser genotype
Haemophilia
History of peptic ulcer
Nasal polyps associated with bronchospasm and NSAIDs
Obstructive pulmonary disease
Peptic ulcer
Pseudomembranous enterocolitis
Respiratory depression
Severe hepatic impairment
Severe renal impairment
Third trimester of pregnancy
Thrombocytopenia

Precautions and Warnings

Allergic disposition
Surgery
Within 2 weeks of discontinuing MAOIs
Adrenal insufficiency
Anaemia
Asthma
Breastfeeding
Bronchospasm
Cardiac failure
Cholelithiasis
Connective tissue disorder
CYP2D6 poor metaboliser genotype
Dehydration
Epileptic disorder
G6PD deficiency
Gall bladder disorder
Gastric mucosa lesion
Gout
Head trauma
Hepatic impairment
History of alcohol abuse
History of bronchospasm
History of drug misuse
Hypotension
Hypothyroidism
Inflammatory bowel disease
Myasthenia gravis
Phaeochromocytoma
Pregnancy
Prostate disorder
Raised intracranial pressure
Renal impairment
Systemic lupus erythematosus
Thyrotoxicosis
Uncontrolled hypertension

Children under 18 years: Increased risk of rare and severe adverse effects
NSAIDs may provoke or exacerbate asthma
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 not to drive until they know how the medicine affects them
Advise patient this medicine may be subject to driving restrictions
Can cause addiction
Discontinue if signs of gastro-intestinal bleeding occur
Risk of gastrointestinal haemorrhage
Discontinue if signs of gastro-intestinal ulceration occur
Excessive use may increase frequency of headache, may require withdrawal
May cause convulsions
May precipitate acute rhinitis
NSAIDs may provoke bronchospasm/urticaria in susceptible patients
May affect results of some laboratory tests
Discuss discontinuation prior to surgery
Discontinue if hypersensitivity reactions occur
Discontinue if patient is attempting to conceive
Avoid long term continuous therapy
For three days use only
Advise patient against the use of opioids during treatment
Advise patient to consult a doctor if symptoms persist despite treatment

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.

Aspirin should not be given to children under 16, unless specifically on the advice of a doctor.

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

Co-codaprin is contraindicated during the third trimester of pregnancy and is cautioned throughout the rest of pregnancy.

Salicylates, such as aspirin, should only be used during pregnancy when the potential benefits justify the possible risks to the foetus. Teratogenic effects have not been observed in humans but animal studies have shown salicylates can cause birth defects including fissure of the spine and skull, facial clefts and malformations of the CNS, viscera and skeleton. Aspirin should be avoided during the last 3 months of pregnancy because it may cause premature closure of the ductus arteriosus, prolong labour, delay birth and contribute to neonatal and maternal bleeding. Maternal ingestion of aspirin during the last two weeks of pregnancy may increase the risk of foetal or neonatal haemorrhage and should therefore be avoided.

Opioids such as codeine cross the placenta, and animal studies have shown delayed ossification in mice and increased resorption in rats. Regular use during pregnancy may cause foetal physical dependence, leading to neonatal withdrawal. Opioids enter foetal circulation during labour and may cause respiratory depression in the neonate. They should therefore be avoided during the late stages of labour and during the delivery of a premature infant.

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

Co-codaprin is cautioned during breastfeeding.

Patients who are breast feeding should not take aspirin as it is excreted in breast milk. Neonates excrete salicylates slowly and are more sensitive to the platelet inhibitory effect of aspirin in addition to the possible risk of Reye's Syndrome.

Codeine is distributed in breast milk in small amounts and therefore it is advisable to avoid administration of opioids in breastfeeding women. If opioid toxicity develops then co-codaprin should be stopped and in severe cases naloxone should be prescribed to reverse the effects.

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

Addiction
Allergic reaction
Anaemia
Angioneurotic oedema
Anti-diuretic effect
Aplastic anaemia
Asthma
Biliary spasm
Blurred vision
Bradycardia
Breathing difficulties
Bronchospasm
CNS excitation
Confusion
Constipation
Convulsions
Deafness
Decreased appetite
Dependence
Depression
Dizziness
Double vision
Drowsiness
Dry mouth
Flushing
Gastric irritation
Gastro-intestinal ulceration
Gastrointestinal bleeding
Haemolytic anaemia
Hallucinations
Headache
Heartburn
Hepatitis
Hypersensitivity reactions
Hypertension
Hypoprothrombinaemia
Hypotension
Hypothermia
Increased sweating
Malaise
Miosis
Mood changes
Nausea
Nightmares
Palpitations
Pancytopenia
Paralytic ileus
Raised intracranial pressure
Rash
Respiratory rate disturbances
Rhinitis
Salicylism
Sleep disturbances
Stomach pain
Tachycardia
Thrombocytopenia
Tinnitus
Tiredness
Tolerance
Toxic megacolon
Trembling
Tremor
Urate kidney stones
Ureteric spasm
Urticaria
Vertigo
Vomiting
Weakness

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:

Aspirin
Salicylate poisoning is usually associated with plasma concentrations >350 mg/L (2.5 mmol/L). Most adult deaths occur in patients whose concentrations exceed 700 mg/L (95.1 mmol/L). Single doses less than 100 mg/kg are unlikely to cause serious poisoning.
Codeine
The effects in overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs.

Signs and Symptoms

Aspirin
Common features include vomiting, dehydration, tinnitus, vertigo, deafness, sweating, warm extremities with bounding pulses, increased respiratory rate and hyperventilation. Some degree of acid-base disturbance is present in most cases.

A mixed respiratory alkalosis and metabolic acidosis with normal or high arterial pH (normal or reduced hydrogen ion concentration) is usual in adults and children over the age of four years. In children aged four years or less, a dominant metabolic acidosis with low arterial pH (raised hydrogen ion concentration) is common. Acidosis may increase salicylate transfer across the blood brain barrier.

Uncommon features include haematemesis, hyperpyrexia, hypoglycaemia, hypokalaemia, thrombocytopaenia, increased INR/PTR, intravascular coagulation, renal failure and non-cardiac pulmonary oedema.

Central nervous system features including confusion, disorientation, coma and convulsions are less common in adults than in children.

Codeine
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

Aspirin
Give activated charcoal if an adult presents within one hour of ingestion of more than 250 mg/kg. The plasma salicylate concentration should be measured, although the severity of poisoning cannot be determined from this alone and the clinical and biochemical features must be taken into account. Elimination is increased by urinary alkalinisation, which is achieved by the administration of 1.26% sodium bicarbonate. The urine pH should be monitored. Correct metabolic acidosis with intravenous 8.4% sodium bicarbonate (first check serum potassium). Forced diuresis should not be used since it does not enhance salicylate excretion and may cause pulmonary oedema.

Haemodialysis is the treatment of choice for severe poisoning and should be considered in patients with plasma salicylate concentrations >700 mg/L (5.1 mmol/L), or lower concentrations associated with severe clinical or metabolic features. Patients under ten years or over 70 have increased risk of salicylate toxicity and may require dialysis at an earlier stage.

Codeine
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: September 2014

Reference Sources

Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press. Accessed on September 4, 2014.

MHRA 19th September 2005 https://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/Informationforlicenceapplicants/Guidance/OverdosesectionsofSPCs/Genericoverdosesections/index.htm
Last accessed: 16 September, 2014

MHRA 19th September 2005
https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON057141
Last accessed: 16 September, 2014

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: 16 September, 2014

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: 16 September, 2014

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: 16 September, 2014

Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications. Accessed on 16 September, 2014.

Summary of Product Characteristics: Codis 500. Reckitt Benckiser healthcare (UK) Ltd. Revised December 2013.

Summary of Product Characteristics: Dispersible Co-codaprin tablets 8/400mg. Actavis UK Ltd. Revised February 2014

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