Drugs List

Therapeutic Indications

Uses

For the treatment of mild to moderate pain including headache, migraine, neuralgia, toothache, sore throat, dysmenorrhoea and aches and pains.

For the symptomatic treatment of muscular pain, sprains and strains, rheumatic pain, sciatica, lumbago, fibrositis, joint swelling and stiffness, influenza, pyrexia and feverish colds.

For the relief of headache with an upset stomach.

Not all presentations are licensed for all indications.

Administration

For oral administration with or after food

Soluble tablets should be dissolved in water before swallowing.

Effervescent tablets should be mixed with water before swallowing.

Contraindications

Patients with peptic ulceration or a history of peptic ulcer

Children under 16 years (see dosage, Children)

Haemophilia or other clotting disorders

Breastfeeding (see Lactation)

Severe renal impairment

Severe hepatic impairment

Pregnancy - Third trimester (see Pregnancy)

Asthma-rhinitis-urticaria-angioedema due to aspirin or other non-steroidal anti-inflammatory drugs.

Precautions and Warnings

Not all presentations are licensed for all indications.

History of gastrointestinal disorders. May induce gastrointestinal haemorrhage

Asthma or history of asthma (non steroidal anti-inflammatory drugs may provoke or exacerbate asthma)

Dehydration

Renal impairment

Hepatic impairment

Uncontrolled hypertension

Elderly

Patients with hereditary glucose 6-phosphate dehydrogenase (G6PD) deficiency due to the risk of haemolysis. Use is usually acceptable up to a dose of at least 1g aspirin daily in most patients but individual response should be monitored carefully.

Allergic disease

Use with caution in alcoholism or in patients with non-cirrhotic alcoholic liver disease

Aspirin should be discontinued several days before scheduled surgery (including dental extractions)

Aspirin may interfere with thyroid function tests
Thyrotoxicosis (may be exacerbated by large doses of salicylates)

Aspirin decreases platelet adhesiveness and increases bleeding time, and so patients should be advised to report any unusual bleeding to their doctor

There is a possible association between aspirin and Reye's syndrome when given to children. Reye's syndrome is a very rare disease, which affects the brain and liver, and can be fatal. For this reason aspirin should not be given to children under 16 years unless specifically indicated (e.g. for Kawasaki's disease)

Pregnancy - first and second trimesters (see Pregnancy section)

Patients should be advised to consult their doctor if symptoms persist for more than 3 days despite treatment

Patients or their carers should seek advice immediately in the event of an overdose, even if the patient seems well because of the risk of delayed, serious liver damage.

Patients should be advised not to exceed the stated dose

Do not administer with any other paracetamol or aspirin containing products

Some brands contain lactose and therefore patients with galactosaemia, glucose-galactose malabsorption syndrome or those who are lactose intolerant should not take this medication.

Some brands contain aspartame and therefore patients with phenylketonuria should be treated with caution.

Some brands may contain significant quantities of sodium; caution in patients requiring a low sodium diet.

CSM Warnings

Do not give aspirin to children under 16 years unless medically indicated (e.g. for Kawasaki syndrome)

Any degree of worsening of asthma may be related to the ingestion of NSAIDs, either prescribed or (in the case of ibuprofen and others) purchased over the counter.

Pregnancy and Lactation

Pregnancy

Paracetamol:
This drug is routinely used during all stages of pregnancy as an analgesic and for pyrexia. Paracetamol crosses the placenta. In therapeutic doses it appears safe for short term use. Paracetamol is the analgesic of choice in pregnancy and is well tolerated. Teratogenic potential in humans was initially suspected, along with an association with gastroschisis, reduction in proportion of preterm birth, possible causative factor for asthma and elevated IgE levels but subsequent investigations have indicated no developmental risk. In therapeutic doses from maternal use, it does not inhibit prostaglandin synthesis and does not appear to be associated with any risks to the embryo or foetus. However, high doses or prolonged exposed should be avoided.

Aspirin:
Low dose treatment with aspirin can be used unrestrictedly for appropriate indications during pregnancy and is the analgesic and antipyretic of second choice in pregnancy. However, the use of chronic or intermittent high doses should be avoided. The drug may be affect maternal and newborn haemostasis mechanisms, leading to an increased risk of haemorrhage. Low doses such as 80mg/day appear to have beneficial effects in pregnancies complicated by systemic lupus erythematosus with antiphospholipid antibodies. High doses however may be related to increased perinatal mortality, intrauterine growth retardation and teratogenic effects. Near term, the drug may prolong gestation and labour and has been used as a tocolytic agent. Women trying to conceive should not use aspirin because of the findings in a variety of animal models that indicate this drug blocks blastocyst implantation.

Caffeine:
Caffeine consumption during pregnancy in moderate amounts does not appear to pose any measurable risk to the foetus. No association with congenital malformations, preterm birth, low birth weight and spontaneous abortions have been proven when the drug is taken in moderation. High doses have been associated with infertility, spontaneous abortions and difficulty in becoming pregnant. However, before any conclusions can be drawn confirmation of these findings is needed (Briggs 2011). Consumption of significantly higher amounts of caffeine does not justify any additional diagnostic procedures. However, consumption should be reduced for the rest of the pregnancy (Schaefer 2007).

Because of the potential for adverse effects on the embryo or foetus, caution should be used when taking this medicine whilst pregnant.

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 14-17 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 ).

Licensed inpregnancy? - No

Recommended for use in pregnancy? - Contraindicated in third trimester, use may be considered during the first and second trimesters although other first line agents may be preferred.

Known human teratogen? - No, not at therapeutic doses

Crosses placenta? - Yes

Lactation

Paracetamol:
The drug is excreted into human breast milk in low concentrations however paracetamol belongs to the group of analgesics of choice during breastfeeding. Adverse effects in breastfed infants appear to be rare and the quantity of drug that passes into the milk is very small, representing only a small proportion of a normal therapeutic infant dose. However, since metabolism and renal excretion are not fully developed in the newborn, accumulation can not be ruled out in the case of long term treatment. Consideration should also be given to any additional dosages of paracetamol the breastfed infant may be receiving directly, to ensure toxicity does not occur.

Aspirin:
Although the occasional single dose of aspirin daily is unlikely to cause any problems in the infant, aspirin should be avoided during breastfeeding, especially in very young infants due to the possible risk of Reye's syndrome, as well as neonatal bleeding due to hyperthrombinaemia.

Caffeine:
Moderate caffeine intake, such as 300mg in 24 hours, is not considered to be of concern during breastfeeding (Schaefer 2007). However, caffeine appears rapidly in human milk after maternal consumption and jitteriness, irritability and poor sleeping patterns have been observed in nursing infants during heavy periods of maternal caffeine consumption. Accumulation may occur in infants when mothers use moderate to heavy amounts of caffeinated beverages as the elimination half life of caffeine is approximately 80 hours in term newborns. Coffee intake of more than 450ml daily may decrease the iron content in breast milk and result in mild iron deficiency anaemia in some breast fed infants.

Due to the potential risk of Reye's syndrome and other serious adverse effects in the newborn, the use of this medication whilst breast feeding is contraindicated.

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

Drug excreted in breast milk? - Yes

Considered suitable or recommended by manufacturer? - No

Drug substance licensed in infants? - Paracetamol = Not in children under 2 months. Aspirin = Not in children under 16 years. Caffeine = Yes

Drug known to affect lactation? - Caffeine may reduce iron content in breast milk.

Side Effects

Gastro-intestinal symptoms
Nausea
Vomiting
Gastro-intestinal haemorrhage
Gastric irritation
Gastro-intestinal ulceration with occult bleeding
Hearing disturbances
Tinnitus
Confusion
Hypersensitivity reactions
Angioedema
Rash
Bronchospasm
Blood disorders
Thrombocytopenic purpura
Agranulocytosis
Increased bleeding tendency
Skin reactions
Subconjunctival haemorrhage
Exacerbation of latent gout
Tremor
Palpitations
Dyspepsia
Hepatotoxicity
Gastric erosions
Insomnia
Restlessness
Melaena
Iron deficiency anaemia
Urticaria
Rhinitis
Dyspnoea
Leucopenia
Neutropenia
Hypoprothrombinaemia
Dizziness
Deafness
Sweating
Pancytopenia
Abdominal pain
Diarrhoea
Gastroesophageal reflux
Headache
Anxiety
Asthma
Gout
Reye's syndrome
Prolonged bleeding
Papillary necrosis
Haematemesis
Irritability
Vertigo
Prothrombin time increased
Methaemoglobinaemia
Pancreatitis
Nervousness
Delirium

Presentation

Tablets containing paracetamol 200mg, aspirin 300mg and caffeine 45mg

Soluble tablets containing paracetamol 200mg, aspirin 300mg and caffeine 45mg (as caffeine citrate 90mg in some brands)

Effervescent tablets containing paracetamol 133mg, aspirin 267mg, caffeine 40mg, sodium hydrogen carbonate 1.606g and citric acid 954mg

Drugs List

Therapeutic Indications

Uses

For the treatment of mild to moderate pain including headache, migraine, neuralgia, toothache, sore throat, dysmenorrhoea and aches and pains.

For the symptomatic treatment of muscular pain, sprains and strains, rheumatic pain, sciatica, lumbago, fibrositis, joint swelling and stiffness, influenza, pyrexia and feverish colds.

For the relief of headache with an upset stomach.

Not all presentations are licensed for all indications.

Dosage

Adults

Elderly

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Administration

For oral administration with or after food

Soluble tablets should be dissolved in water before swallowing.

Effervescent tablets should be mixed with water before swallowing.

Contraindications

Patients with peptic ulceration or a history of peptic ulcer

Children under 16 years (see dosage, Children)

Haemophilia or other clotting disorders

Breastfeeding (see Lactation)

Severe renal impairment

Severe hepatic impairment

Pregnancy - Third trimester (see Pregnancy)

Asthma-rhinitis-urticaria-angioedema due to aspirin or other non-steroidal anti-inflammatory drugs.

Precautions and Warnings

Not all presentations are licensed for all indications.

History of gastrointestinal disorders. May induce gastrointestinal haemorrhage

Asthma or history of asthma (non steroidal anti-inflammatory drugs may provoke or exacerbate asthma)

Dehydration

Renal impairment

Hepatic impairment

Uncontrolled hypertension

Elderly

Patients with hereditary glucose 6-phosphate dehydrogenase (G6PD) deficiency due to the risk of haemolysis. Use is usually acceptable up to a dose of at least 1g aspirin daily in most patients but individual response should be monitored carefully.

Allergic disease

Use with caution in alcoholism or in patients with non-cirrhotic alcoholic liver disease

Aspirin should be discontinued several days before scheduled surgery (including dental extractions)

Aspirin may interfere with thyroid function tests
Thyrotoxicosis (may be exacerbated by large doses of salicylates)

Aspirin decreases platelet adhesiveness and increases bleeding time, and so patients should be advised to report any unusual bleeding to their doctor

There is a possible association between aspirin and Reye's syndrome when given to children. Reye's syndrome is a very rare disease, which affects the brain and liver, and can be fatal. For this reason aspirin should not be given to children under 16 years unless specifically indicated (e.g. for Kawasaki's disease)

Pregnancy - first and second trimesters (see Pregnancy section)

Patients should be advised to consult their doctor if symptoms persist for more than 3 days despite treatment

Patients or their carers should seek advice immediately in the event of an overdose, even if the patient seems well because of the risk of delayed, serious liver damage.

Patients should be advised not to exceed the stated dose

Do not administer with any other paracetamol or aspirin containing products

Some brands contain lactose and therefore patients with galactosaemia, glucose-galactose malabsorption syndrome or those who are lactose intolerant should not take this medication.

Some brands contain aspartame and therefore patients with phenylketonuria should be treated with caution.

Some brands may contain significant quantities of sodium; caution in patients requiring a low sodium diet.

CSM Warnings

Do not give aspirin to children under 16 years unless medically indicated (e.g. for Kawasaki syndrome)

Any degree of worsening of asthma may be related to the ingestion of NSAIDs, either prescribed or (in the case of ibuprofen and others) purchased over the counter.

Pregnancy and Lactation

Pregnancy

Paracetamol:
This drug is routinely used during all stages of pregnancy as an analgesic and for pyrexia. Paracetamol crosses the placenta. In therapeutic doses it appears safe for short term use. Paracetamol is the analgesic of choice in pregnancy and is well tolerated. Teratogenic potential in humans was initially suspected, along with an association with gastroschisis, reduction in proportion of preterm birth, possible causative factor for asthma and elevated IgE levels but subsequent investigations have indicated no developmental risk. In therapeutic doses from maternal use, it does not inhibit prostaglandin synthesis and does not appear to be associated with any risks to the embryo or foetus. However, high doses or prolonged exposed should be avoided.

Aspirin:
Low dose treatment with aspirin can be used unrestrictedly for appropriate indications during pregnancy and is the analgesic and antipyretic of second choice in pregnancy. However, the use of chronic or intermittent high doses should be avoided. The drug may be affect maternal and newborn haemostasis mechanisms, leading to an increased risk of haemorrhage. Low doses such as 80mg/day appear to have beneficial effects in pregnancies complicated by systemic lupus erythematosus with antiphospholipid antibodies. High doses however may be related to increased perinatal mortality, intrauterine growth retardation and teratogenic effects. Near term, the drug may prolong gestation and labour and has been used as a tocolytic agent. Women trying to conceive should not use aspirin because of the findings in a variety of animal models that indicate this drug blocks blastocyst implantation.

Caffeine:
Caffeine consumption during pregnancy in moderate amounts does not appear to pose any measurable risk to the foetus. No association with congenital malformations, preterm birth, low birth weight and spontaneous abortions have been proven when the drug is taken in moderation. High doses have been associated with infertility, spontaneous abortions and difficulty in becoming pregnant. However, before any conclusions can be drawn confirmation of these findings is needed (Briggs 2011). Consumption of significantly higher amounts of caffeine does not justify any additional diagnostic procedures. However, consumption should be reduced for the rest of the pregnancy (Schaefer 2007).

Because of the potential for adverse effects on the embryo or foetus, caution should be used when taking this medicine whilst pregnant.

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 14-17 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 ).

Licensed inpregnancy? - No

Recommended for use in pregnancy? - Contraindicated in third trimester, use may be considered during the first and second trimesters although other first line agents may be preferred.

Known human teratogen? - No, not at therapeutic doses

Crosses placenta? - Yes

Lactation

Paracetamol:
The drug is excreted into human breast milk in low concentrations however paracetamol belongs to the group of analgesics of choice during breastfeeding. Adverse effects in breastfed infants appear to be rare and the quantity of drug that passes into the milk is very small, representing only a small proportion of a normal therapeutic infant dose. However, since metabolism and renal excretion are not fully developed in the newborn, accumulation can not be ruled out in the case of long term treatment. Consideration should also be given to any additional dosages of paracetamol the breastfed infant may be receiving directly, to ensure toxicity does not occur.

Aspirin:
Although the occasional single dose of aspirin daily is unlikely to cause any problems in the infant, aspirin should be avoided during breastfeeding, especially in very young infants due to the possible risk of Reye's syndrome, as well as neonatal bleeding due to hyperthrombinaemia.

Caffeine:
Moderate caffeine intake, such as 300mg in 24 hours, is not considered to be of concern during breastfeeding (Schaefer 2007). However, caffeine appears rapidly in human milk after maternal consumption and jitteriness, irritability and poor sleeping patterns have been observed in nursing infants during heavy periods of maternal caffeine consumption. Accumulation may occur in infants when mothers use moderate to heavy amounts of caffeinated beverages as the elimination half life of caffeine is approximately 80 hours in term newborns. Coffee intake of more than 450ml daily may decrease the iron content in breast milk and result in mild iron deficiency anaemia in some breast fed infants.

Due to the potential risk of Reye's syndrome and other serious adverse effects in the newborn, the use of this medication whilst breast feeding is contraindicated.

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

Drug excreted in breast milk? - Yes

Considered suitable or recommended by manufacturer? - No

Drug substance licensed in infants? - Paracetamol = Not in children under 2 months. Aspirin = Not in children under 16 years. Caffeine = Yes

Drug known to affect lactation? - Caffeine may reduce iron content in breast milk.

Effects on Ability to Drive and Operate Machinery

None known

Counselling

Patients and parents should be advised not to give aspirin to children under 16 years unless on specific medical advice

Advise patients not to exceed the stated dose.

Advise patients not to take any other products containing paracetamol

Advise patients to seek medical advice in the event of overdose even if they feel well due to the risk of delayed, serious liver damage.

Advise patients to seek medical advice if symptoms persist beyond 3 days

Patients should be advised to report any unusual bleeding to their doctor.

Side Effects

Gastro-intestinal symptoms
Nausea
Vomiting
Gastro-intestinal haemorrhage
Gastric irritation
Gastro-intestinal ulceration with occult bleeding
Hearing disturbances
Tinnitus
Confusion
Hypersensitivity reactions
Angioedema
Rash
Bronchospasm
Blood disorders
Thrombocytopenic purpura
Agranulocytosis
Increased bleeding tendency
Skin reactions
Subconjunctival haemorrhage
Exacerbation of latent gout
Tremor
Palpitations
Dyspepsia
Hepatotoxicity
Gastric erosions
Insomnia
Restlessness
Melaena
Iron deficiency anaemia
Urticaria
Rhinitis
Dyspnoea
Leucopenia
Neutropenia
Hypoprothrombinaemia
Dizziness
Deafness
Sweating
Pancytopenia
Abdominal pain
Diarrhoea
Gastroesophageal reflux
Headache
Anxiety
Asthma
Gout
Reye's syndrome
Prolonged bleeding
Papillary necrosis
Haematemesis
Irritability
Vertigo
Prothrombin time increased
Methaemoglobinaemia
Pancreatitis
Nervousness
Delirium

Effects on Laboratory Tests

Aspirin may interfere with thyroid function tests

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 represented below:

Salicylates and 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 (5.1 mmol/L). Single doses less than 100 mg/kg are unlikely to cause serious poisoning.

Paracetamol:

Liver damage is possible in patients who have taken 75mg/kg or more of paracetamol in less than an hour, and these patients should be referred to hospital. To avoid underestimating the potentially toxic paracetamol dose ingested by obese patients who weigh more than 110kg, a bodyweight of 110kg (rather than the actual bodyweight) should be used to calculate the total dose of paracetamol ingested in mg/kg.

Signs and Symptoms

Salicylates and 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.

Paracetamol:

Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema, and death. Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria and proteinuria, may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.

Treatment

Salicylates and 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.

Paracetamol:

Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage. Management should be in accordance with established treatment guidelines.

Treatment with activated charcoal should be considered if the overdose in excess of 150mg/kg has been taken within 1 hour. Treatment with acetylcysteine is used up to, and possibly beyond, 24 hours of ingesting paracetamol. It is most effective if given within 8 hours of ingestion, after which effectiveness declines. If required, the patient should be given intravenous acetylcysteine, in line with the established dosage schedule. Giving acetylcysteine by mouth (unlicensed route) is an alternative if intravenous access is not possible. Acetylcysteine can be given irrespective of the plasma paracetamol concentration:
in circumstances where the overdose is staggered or there is doubt over the time of paracetamol ingestion; or
in overdose with a timed plasma paracetamol concentration on or above a single treatment line joining points of 100mg/L at 4 hours and 15mg/L at 15 hours nomogram (https://www.mhra.gov.uk/home/groups/pl-p/documents/drugsafetymessage/con184396.pdf), regardless of risk factors of hepatotoxicity.

Plasma paracetamol concentration should be measured at 4 hours or later after ingestion (earlier concentration are unreliable). If vomiting is not a problem, and overdose has been taken within 10-12 hours, oral methionine may be a suitable alternative for remote areas outside hospital. Management of patients who present beyond 24 hours from ingestion or with serious hepatic dysfunction should be discussed with the NPIS (https://www.npis.org/) or a liver unit.

Shelf Life and Storage

Store at or below 25 degrees C in the original packaging.

Further Information

Last Full Review Date: June 2012

Reference Sources

British National Formulary, 64th Edition (2012) Pharmaceutical Press, London.

BNF for Children (2012-2013) Pharmaceutical Press, London.

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.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Summary of Product Characteristics: Anadin Extra Tablets. Wyeth Consumer Healthcare. Revised September 2010.

Summary of Product Characteristics. Anadin Extra Soluble Tablets. Wyeth Consumer Healthcare. Revised July 2011.

Summary of Product Characteristics: Alka-Seltzer XS. Bayer Diagnostics Manufacturing Ltd. Revised February 2010.

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
Acetaminophen Last revised: October 2nd, 2012
Last accessed: November 19, 2012

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
Caffeine Last revised: October 2nd, 2012
Last accessed: November 19, 2012

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
Aspirin Last revised: October 2nd, 2012
Last accessed: November 19, 2012

MHRA 10th September 2012
https://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/Informationforlicenceapplicants/Guidance/OverdosesectionsofSPCs/Genericoverdosesections/Paracetamol/index.htm
Last accessed: September 20, 2012

MHRA 19th September 2005
https://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/Informationforlicenceapplicants/Guidance/OverdosesectionsofSPCs/Genericoverdosesections/Salicylatesandaspirin/index.htm
Last accessed: September 20, 2012