Drugs List

Therapeutic Indications

Uses

Pain - mild to moderate
Pyrexia

Contraindications

Children under 12 years

Precautions and Warnings

Restricted sodium intake
Alcoholism
Breastfeeding
Hepatic impairment
Hereditary fructose intolerance
Non-cirrhotic alcoholic liver disease
Pregnancy
Renal impairment

Sodium content of formulation may be significant
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Overdosage causes liver damage
Prolonged use and excessive doses may cause hepatic necrosis
Seek urgent medical advice in event of overdose, even if patient feels well
Avoid excessive intake of tea, coffee or other stimulants
Advise patient to consult a doctor if symptoms persist despite treatment
Patients should not exceed recommended dose

Pregnancy and Lactation

Pregnancy

Caution is advised in pregnancy.

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.

Caffeine crosses the placenta, and foetal blood and tissue levels similar to maternal concentrations are achieved. When used in moderation, no association with congenital malformations, spontaneous abortions, preterm birth and low birth weight has been proven.

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

Caution is advised during breastfeeding.

Paracetamol is excreted into human breast milk in low concentrations, however, it 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.

Caffeine is excreted into breast milk. Caffeine intake should be monitored by lactating women, who should be aware of the many sources of caffeine contained in beverages as well as medication.

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

Agranulocytosis
Angioedema
Blood dyscrasias
Bronchospasm
Dizziness
Hepatic impairment
Hypersensitivity reactions including anaphylaxis
Nervousness
Rash
Stevens-Johnson syndrome
Thrombocytopenia
Toxic epidermal necrolysis

Presentation

Oral formulations of paracetamol and caffeine

Drugs List

Therapeutic Indications

Uses

Pain - mild to moderate
Pyrexia

Dosage

Adults

Elderly

Children

Contraindications

Children under 12 years

Precautions and Warnings

Restricted sodium intake
Alcoholism
Breastfeeding
Hepatic impairment
Hereditary fructose intolerance
Non-cirrhotic alcoholic liver disease
Pregnancy
Renal impairment

Sodium content of formulation may be significant
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Overdosage causes liver damage
Prolonged use and excessive doses may cause hepatic necrosis
Seek urgent medical advice in event of overdose, even if patient feels well
Avoid excessive intake of tea, coffee or other stimulants
Advise patient to consult a doctor if symptoms persist despite treatment
Patients should not exceed recommended dose

Pregnancy and Lactation

Pregnancy

Caution is advised in pregnancy.

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.

Caffeine crosses the placenta, and foetal blood and tissue levels similar to maternal concentrations are achieved. When used in moderation, no association with congenital malformations, spontaneous abortions, preterm birth and low birth weight has been proven.

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

Caution is advised during breastfeeding.

Paracetamol is excreted into human breast milk in low concentrations, however, it 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.

Caffeine is excreted into breast milk. Caffeine intake should be monitored by lactating women, who should be aware of the many sources of caffeine contained in beverages as well as medication.

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

Agranulocytosis
Angioedema
Blood dyscrasias
Bronchospasm
Dizziness
Hepatic impairment
Hypersensitivity reactions including anaphylaxis
Nervousness
Rash
Stevens-Johnson syndrome
Thrombocytopenia
Toxic epidermal necrolysis

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:

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

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

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.

Further Information

Last Full Review Date: September 2013.

Reference Sources

British National Formulary, 66th Edition (September 2013-March 2014) Pharmaceutical Press, London.

BNF for Children (2013-2014) 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.

Summary of Product Characteristics: Beechams Cold Relief Orange Flavour Effervescent Tablets. GlaxoSmithKline Consumer Healthcare. Revised December 2012.

Summary of Product Characteristics: Hedex Extra tablets. Omega Pharma Ltd. Revised December 2012.

Summary of Product Characteristics: Mandanol Plus tablets. M & A Pharmachem Ltd. Revised November 2010.

Summary of Product Characteristics: Panadol Extra Advance tablets. GlaxoSmithKline Consumer Healthcare. Revised March 2012.
Summary of Product Characteristics: Panadol Extra soluble tablets. GlaxoSmithKline Consumer Healthcare. Revised April 2010.

Summary of Product Characteristics: Solpadeine Headache soluble tablets. GlaxoSmithKline Consumer Healthcare. Revised April 2010.

MHRA 10th September 2012
https://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/Informationforlicenceapplicants/Guidance/OverdosesectionsofSPCs/Genericoverdosesections/Paracetamol/index.htm
Last accessed: September 11, 2013

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: September 7th, 2013
Last accessed: September 11th, 2013