Paracetamol
| 1. NAME |
| 1.1 Substance |
| 1.2 Group |
| 1.3 Synonyms |
| 1.4 Identification numbers |
| 1.4.1 CAS number |
| 1.4.2 Other numbers |
| 1.5 Main brand names, main trade names |
| 1.6 Main manufacturers, main importers |
| 2. SUMMARY |
| 2.1 Main risks and target organs |
| 2.2 Summary of clinical effects |
| 2.3 Diagnosis |
| 2.4 First aid measures and management principles |
| 3. PHYSICO-CHEMICAL PROPERTIES |
| 3.1 Origin of the substance |
| 3.2 Chemical structure |
| 3.3 Physical properties |
| 3.3.1 Colour |
| 3.3.2 State/Form |
| 3.3.3 Description |
| 3.4 Other characteristics |
| 3.4.1 Shelf-life of the substance |
| 3.4.2 Storage conditions |
| 4. USES |
| 4.1 Indications |
| 4.1.1 Indications |
| 4.1.2 Description |
| 4.2 Therapeutic dosage |
| 4.2.1 Adults |
| 4.2.2 Children |
| 4.3 Contraindications |
| 5. ROUTES OF EXPOSURE |
| 5.1 Oral |
| 5.2 Inhalation |
| 5.3 Dermal |
| 5.4 Eye |
| 5.5 Parenteral |
| 5.6 Other |
| 6. KINETICS |
| 6.1 Absorption by route of exposure |
| 6.2 Distribution by route of exposure |
| 6.3 Biological half-life by route of exposure |
| 6.4 Metabolism |
| 6.5 Elimination and excretion |
| 7. PHARMACOLOGY AND TOXICOLOGY |
| 7.1 Mode of action |
| 7.1.1 Toxicodynamics |
| 7.1.2 Pharmacodynamics |
| 7.2 Toxicity |
| 7.2.1 Human data |
| 7.2.1.1 Adults |
| 7.2.1.2 Children |
| 7.2.2 Relevant animal data |
| 7.2.3 Relevant in vitro data |
| 7.3 Carcinogenicity |
| 7.4 Teratogenicity |
| 7.5 Mutagenicity |
| 7.6 Interactions |
| 7.7 Main adverse effects |
| 8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS |
| 8.1 Material sampling plan |
| 8.1.1 Sampling and specimen collection |
| 8.1.1.1 Toxicological analyses |
| 8.1.1.2 Biomedical analyses |
| 8.1.1.3 Arterial blood gas analysis |
| 8.1.1.4 Haematological analyses |
| 8.1.1.5 Other (unspecified) analyses |
| 8.1.2 Storage of laboratory samples and specimens |
| 8.1.2.1 Toxicological analyses |
| 8.1.2.2 Biomedical analyses |
| 8.1.2.3 Arterial blood gas analysis |
| 8.1.2.4 Haematological analyses |
| 8.1.2.5 Other (unspecified) analyses |
| 8.1.3 Transport of laboratory samples and specimens |
| 8.1.3.1 Toxicological analyses |
| 8.1.3.2 Biomedical analyses |
| 8.1.3.3 Arterial blood gas analysis |
| 8.1.3.4 Haematological analyses |
| 8.1.3.5 Other (unspecified) analyses |
| 8.2 Toxicological Analyses and Their Interpretation |
| 8.2.1 Tests on toxic ingredient(s) of material |
| 8.2.1.1 Simple Qualitative Test(s) |
| 8.2.1.2 Advanced Qualitative Confirmation Test(s) |
| 8.2.1.3 Simple Quantitative Method(s) |
| 8.2.1.4 Advanced Quantitative Method(s) |
| 8.2.2 Tests for biological specimens |
| 8.2.2.1 Simple Qualitative Test(s) |
| 8.2.2.2 Advanced Qualitative Confirmation Test(s) |
| 8.2.2.3 Simple Quantitative Method(s) |
| 8.2.2.4 Advanced Quantitative Method(s) |
| 8.2.2.5 Other Dedicated Method(s) |
| 8.2.3 Interpretation of toxicological analyses |
| 8.3 Biomedical investigations and their interpretation |
| 8.3.1 Biochemical analysis |
| 8.3.1.1 Blood, plasma or serum |
| 8.3.1.2 Urine |
| 8.3.1.3 Other fluids |
| 8.3.2 Arterial blood gas analyses |
| 8.3.3 Haematological analyses |
| 8.3.4 Interpretation of biomedical investigations |
| 8.4 Other biomedical (diagnostic) investigations and their interpretation |
| 8.5 Overall interpretation of all toxicological analyses and toxicological investigations |
| 8.6 References |
| 9. CLINICAL EFFECTS |
| 9.1 Acute poisoning |
| 9.1.1 Ingestion |
| 9.1.2 Inhalation |
| 9.1.3 Skin exposure |
| 9.1.4 Eye contact |
| 9.1.5 Parenteral exposure |
| 9.1.6 Other |
| 9.2 Chronic poisoning |
| 9.2.1 Ingestion |
| 9.2.2 Inhalation |
| 9.2.3 Skin exposure |
| 9.2.4 Eye contact |
| 9.2.5 Parenteral exposure |
| 9.2.6 Other |
| 9.3 Course, prognosis, cause of death |
| 9.4 Systematic description of clinical effects |
| 9.4.1 Cardiovascular |
| 9.4.2 Respiratory |
| 9.4.3 Neurological |
| 9.4.3.1 Central nervous system (CNS) |
| 9.4.3.2 Peripheral nervous system |
| 9.4.3.3 Autonomic nervous system |
| 9.4.3.4 Skeletal and smooth muscle |
| 9.4.4 Gastrointestinal |
| 9.4.5 Hepatic |
| 9.4.6 Urinary |
| 9.4.6.1 Renal |
| 9.4.6.2 Other |
| 9.4.7 Endocrine and reproductive systems |
| 9.4.8 Dermatological |
| 9.4.9 Eye, ear, nose, throat: local effects |
| 9.4.10 Haematological |
| 9.4.11 Immunological |
| 9.4.12 Metabolic |
| 9.4.12.1 Acid-base disturbances |
| 9.4.12.2 Fluid and electrolyte disturbances |
| 9.4.12.3 Others |
| 9.4.13 Allergic reactions |
| 9.4.14 Other clinical effects |
| 9.4.15 Special risks |
| 9.5 Other |
| 9.6 Summary |
| 10. MANAGEMENT |
| 10.1 General principles |
| 10.2 Life supportive procedures and symptomatic/specific treatment |
| 10.3 Decontamination |
| 10.4 Enhanced elimination |
| 10.5 Antidote treatment |
| 10.5.1 Adults |
| 10.5.2 Children |
| 10.6 Management discussion |
| 11. ILLUSTRATIVE CASES |
| 11.1 Case reports from literature |
| 12. Additional information |
| 12.1 Specific preventive measures |
| 12.2 Other |
| 13. REFERENCES |
| 14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES) |
Paracetamol
International Programme on Chemical Safety
Poisons Information Monograph 396
Pharmaceutical
This Monograph has the following sections
completed: 1, 2, 3, 5, 7.2, 7.4, 9 & 10.
1. NAME
1.1 Substance
Paracetamol
1.2 Group
1.3 Synonyms
4-Hydroxyanilid kyseliny octove;
Abensanil; Acamol;
Acetagesic; Acetalgin;
Acetaminofen; Acetaminophen;
Algotropyl; Alvedon; Amadil;
Anaflon; Anelix; Apamid;
Apamide; APAP; Ben-u-ron;
Bickie-mol; Calpol; Cetadol;
Clixodyne; Datril;
Dial-a-gesic; Dirox;
Dymadon; Eneril; Excedrin;
Febrilix; Febro-gesic;
Febrolin; Fendon; Finimal;
Hedex; Homoolan; Lestemp;
Liquagesic; Lonarid; Lyteca;
Lyteca syrup; Multin; NAPA;
Napafen; Napap; Naprinol;
NCI-C55801; Nobedon; Pacemo;
Panadol; Panets;
Paracetamole; Paracetamolo;
Parmol; Pedric; Phendon;
Pyrinazine; SK-Apap;
Tabalgin; Tapar; Temlo;
Tempanal; Tempra; Tralgon;
Tussapap; Tylenol; Valadol;
Valgesic
1.4 Identification numbers
1.4.1 CAS number
103-90-2
1.4.2 Other numbers
NIOSH/RTECS: AE4200000
1.5 Main brand names, main trade names
1.6 Main manufacturers, main importers
2. SUMMARY
2.1 Main risks and target organs
The clinical course of paracetamol poisoning is often
classified into four stages. During stages one and two the
patient may present minor signs of toxicity, including nausea
and vomiting, or they may be asymptomatic. During stage
three, hepatic toxicity and subsequent multi-system failure
and death may occur. Hepatic recovery should occur in
patients that survive stage three.
2.2 Summary of clinical effects
Paracetamol poisoning may occur if a child has ingested
more than 150mg/kg or an adult has ingested more than 150
mg/kg or 7.5g and over.
Stage I (0-24 hours)
During this stage patients may experience nausea and vomiting
or may be asymptomatic.
Stage II (24-72 hours)
During this stage patients may be asymptomatic although
increase in transaminases, bilirubin and prothrombin time may
begin to occur.
Stage III (72-96 hours)
Fuminant hepatic and multi-system fail may occur.
Stage IV (96 hours - two weeks)
Hepatic recovery should occur in patients that survive stage
three.
2.3 Diagnosis
If the time of ingestion is known, a paracetamol serum
concentration should be obtained at least 4 hours or longer
after ingestion. If the time of the ingestion is unknown and
thought to be greater than 4 hours, the paracetamol
concentration should be measured immediately upon
presentation. Paracetamol serum concentrations should be
based on the treatment nomogram (see Figure 1, Section 1.4,
of the Antidotes for poisoning by Paracetamol).
2.4 First aid measures and management principles
Support airway, breathing and circulation. Management of
paracetamol poisoning may include gastrointestinal
decontamination with one of the following: syrup of ipecac
induced emesis, gastric lavage or administration of activated
charcoal. N-acetylcysteine is the proven antidote for
paracetamol poisoning and is most effective when administered
within 8 hours after the initial ingestion of the poison.
Although N-acetylcysteine has been administered up to and
beyond 72 hours after ingestion. Some centres have used
methionine as an alternative to NAC during the first 8 hours
after ingestion (see Antidotes for poisoning by Paracetamol).
Haemodialysis and haemoperfusion have not been proven to be
effective in paracetamol poisoning.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Synthetic
3.2 Chemical structure
Chemical Name: N-Acetyl-p-aminophenol
Other chemical names:
4'-Hydroxyacetanilide
4'-Hydroxyacetanilide Parmol
4-Acetamidophenol
4-Hydroxyacetanilide
Acetamide, N-(4-hydroxyphenyl)-
Acetamide, N-(p-hydroxyphenyl)-
N-(4-Hydroxyphenyl)acetamide
N-(Hydroxy-4 phenyl)acetamide
N-(p-Fluorophenyl)-beta-methyl-1-pyrrolidinepropionamide
N-Acetyl-4-aminophenol
4-Acetaminophenol
p-Acetamidophenol
p-Acetaminophenol
p-Acetylaminophenol
p-Hydroxyacetanilide
p-Acetamido-phenol
Molecular formula: C8H9NO2
Molecular weight: 151.2
3.3 Physical properties
3.3.1 Colour
White
3.3.2 State/Form
Solid-crystals
3.3.3 Description
Melting point 169 to 170.5
Solubility in water: very slightly soluble in cold
water but greater solubility in hot water.
Solubility in organic solvents: soluble in methanol,
ethanol, dimethylformamide, ethylene dichloride,
acetone, ethyl acetate. Slightly soluble in ether.
Insoluble in petroleum ether, pentane, benzene.
(Budavari, 1996).
3.4 Other characteristics
3.4.1 Shelf-life of the substance
3.4.2 Storage conditions
4. USES
4.1 Indications
4.1.1 Indications
4.1.2 Description
4.2 Therapeutic dosage
4.2.1 Adults
4.2.2 Children
4.3 Contraindications
5. ROUTES OF EXPOSURE
5.1 Oral
The main route of exposure to paretamol.
5.2 Inhalation
Not relevant.
5.3 Dermal
Not relevant.
5.4 Eye
Not relevant.
5.5 Parenteral
Not relevant.
5.6 Other
Paracetamol can be administered rectally.
6. KINETICS
6.1 Absorption by route of exposure
6.2 Distribution by route of exposure
6.3 Biological half-life by route of exposure
6.4 Metabolism
6.5 Elimination and excretion
7. PHARMACOLOGY AND TOXICOLOGY
7.1 Mode of action
7.1.1 Toxicodynamics
7.1.2 Pharmacodynamics
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
Susceptibility to paracetamol
overdose varies. In healthy adults a dose of
150mg/kg or 7.5 g or more in total may be
hepatotoxic. Doses of >350mg/kg would
usually be expected to cause severe liver
damage in almost all cases (Prescott, 1983).
The acute toxic dose for high risk patients
(for example, liver disease) is unknown.
7.2.1.2 Children
Young children seem to be less
susceptible to hepatotoxicity following
paracetamol overdose than adults. The exact
reasons are unclear. It is thought that
children may have a more efficient
detoxification pathway with a faster turnover
rate of glutathione (Rumack 1985; Penna and
Buchanan 1991) or increased sulphate
conjugation of acetaminophen (Miller et al.,
1976).
7.2.2 Relevant animal data
7.2.3 Relevant in vitro data
7.3 Carcinogenicity
7.4 Teratogenicity
Although paracetamol does cross the placenta the
occasional use of therapeutic doses in healthy women does not
seem to be associated with an increased risk of malformation
and has not been proved to be teratogenic.
There seems to be the same degree of renal and hepatotoxicity
in the baby as in the mother, so large doses of paracetamol
that cause severe maternal toxicity have been associated with
foetal kidney and liver damage. There is structural damage
(i.e. affecting organ formation) in a 1st trimester exposure
and functional damage (i.e. affecting organ maturation and/or
function) in 2nd and 3rd trimester exposures. There is also
an association with foetal anaemia and neonatal jaundice if
the overdose is taken near term.
7.5 Mutagenicity
7.6 Interactions
7.7 Main adverse effects
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
8.1.1.2 Biomedical analyses
8.1.1.3 Arterial blood gas analysis
8.1.1.4 Haematological analyses
8.1.1.5 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
8.1.2.1 Toxicological analyses
8.1.2.2 Biomedical analyses
8.1.2.3 Arterial blood gas analysis
8.1.2.4 Haematological analyses
8.1.2.5 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
8.1.3.1 Toxicological analyses
8.1.3.2 Biomedical analyses
8.1.3.3 Arterial blood gas analysis
8.1.3.4 Haematological analyses
8.1.3.5 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple Qualitative Test(s)
8.2.1.2 Advanced Qualitative Confirmation Test(s)
8.2.1.3 Simple Quantitative Method(s)
8.2.1.4 Advanced Quantitative Method(s)
8.2.2 Tests for biological specimens
8.2.2.1 Simple Qualitative Test(s)
8.2.2.2 Advanced Qualitative Confirmation Test(s)
8.2.2.3 Simple Quantitative Method(s)
8.2.2.4 Advanced Quantitative Method(s)
8.2.2.5 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
8.3.1.1 Blood, plasma or serum
"Basic analyses"
"Dedicated analyses"
"Optional analyses"
8.3.1.2 Urine
"Basic analyses"
"Dedicated analyses"
"Optional analyses"
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
8.3.3 Haematological analyses
"Basic analyses"
"Dedicated analyses"
"Optional analyses"
8.3.4 Interpretation of biomedical investigations
8.4 Other biomedical (diagnostic) investigations and their
interpretation
8.5 Overall interpretation of all toxicological analyses and
toxicological investigations
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
Paracetamol poisoning usually occurs in four stages:
Stage I (0-24 hours)
During this stage, the patient may be asymptomatic or
experience gastrointestinal effects including
anorexia, nausea and vomiting. Pallor, diaphoresis and
malaise may also be present.
Stage II (24-72 hours)
Patients may be asymptomatic. They may experience
right upper quadrant pain during this phase.
Laboratory evidence of paracetamol poisoning may begin
to occur. This includes increases in hepatic
transaminases including AST and ALT, prolongation of
the PT and increases in bilirubin.
Stage III (72-96 hours)
Fulminant hepatic toxicity may occur. This includes
significant increases in transaminases and bilirubin
as well as significant prolongation of PT. Liver
biopsy will reveal a centrilobular necrosis.
Elevations in serum creatinine and BUN may also occur
during this phase. Decreases in cholesterol, glucose
and albumin are also observed. There may be laboratory
evidence of a metabolic acidosis. Clinical
presentation often includes nausea and vomiting, right
upper quadrant abdominal pain, jaundice and
coagulation defects followed by hepatic encephalopathy
and coma. Renal failure and cardiac involvement may
occur during this stage. Death is due to hepatic
failure and is usually preceded by an acidosis and
oliguria.
Stage IV (96 hours - 2 weeks)
Resolution of hepatic dysfunction occurs in those
patients who do not die or require liver transplant
during Phase III.
9.1.2 Inhalation
9.1.3 Skin exposure
9.1.4 Eye contact
9.1.5 Parenteral exposure
9.1.6 Other
9.2 Chronic poisoning
9.2.1 Ingestion
9.2.2 Inhalation
9.2.3 Skin exposure
9.2.4 Eye contact
9.2.5 Parenteral exposure
9.2.6 Other
9.3 Course, prognosis, cause of death
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
9.4.2 Respiratory
9.4.3 Neurological
9.4.3.1 Central nervous system (CNS)
9.4.3.2 Peripheral nervous system
9.4.3.3 Autonomic nervous system
9.4.3.4 Skeletal and smooth muscle
9.4.4 Gastrointestinal
9.4.5 Hepatic
9.4.6 Urinary
9.4.6.1 Renal
9.4.6.2 Other
9.4.7 Endocrine and reproductive systems
9.4.8 Dermatological
9.4.9 Eye, ear, nose, throat: local effects
9.4.10 Haematological
9.4.11 Immunological
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
9.4.12.2 Fluid and electrolyte disturbances
9.4.12.3 Others
9.4.13 Allergic reactions
9.4.14 Other clinical effects
9.4.15 Special risks
There may be an increased risk of spontaneous
abortion with first trimester exposures.
Paracetamol is not contraindicated during breast feeding.
9.5 Other
9.6 Summary
10. MANAGEMENT
10.1 General principles
Following provision of necessary supportive care,
management of paracetamol toxicity involves gastric
decontamination for recent exposures, laboratory analysis to
determine the degree of toxicity, administration of specific
antidotes such as N-acetylcysteine and more involved
supportive care in those patients who experience hepatic and
multi-system toxicities.
10.2 Life supportive procedures and symptomatic/specific treatment
Symptomatic and supportive care should be provided.
Laboratory Analysis: If a child has ingested more than
150mg/kg or an adult has ingested more than 150 mg/kg or 7.5g
and over, a blood paracetamol concentration should be
measured 4 hours after the ingestion. If a potentially toxic
paracetamol ingestion has occurred and the time of the
ingestion is unknown, a blood paracetamol concentration
should be measured immediately upon presentation. Once the
paracetamol concentration is available, assess the risk of
the patient developing toxicity by comparing the plasma
paracetamol concentration to the time after ingestion using
the treatment nomogram (see Figure 1, Section 1.4, of the
Antidotes for poisoning by Paracetamol).
Some centres treat at half the level if the patient is in a
high risk group. If a paracetamol concentration is not available
within 8 hours of the ingestion, then initiate treatment
without awaiting the level. Stop treatment if their paracetamol
level is non-toxic.
Other essential laboratory studies that should be obtained in
the patient who has a toxic paracetamol serum concentration:
hepatic transaminases including AST and ALT, PT and INR,
bilirubin, blood glucose, serum creatinine and BUN. In
patients with signs of serious toxicity the following should
also be obtained: arterial blood gas, albumin, cholesterol,
complete blood count and a complete coagulation profile.
10.3 Decontamination
Syrup of ipecac can be used to induce emesis in
children if a potentially toxic exposure has occurred within
30 minutes. In adults gastric lavage may be used if the
ingestion is massive and has occurred within 1 hour.
Activated charcoal adsorbs acetaminophen. The paediatric
dose is 1 gram/kg and the adult dose of is 25 to 50g.
10.4 Enhanced elimination
Haemodialysis and haemoperfusion have not been shown to
be effective in removing paracetamol.
10.5 Antidote treatment
10.5.1 Adults
N-Acetylcysteine (please also see Antidotes for
poisoning by Paracetamol):
N-acetylcysteine (NAC) is the antidote of choice for
paracetamol toxicity. NAC acts as a glutathione
substitute, increases glutathione synthesis and
increases sulphate conjugation of acetaminophen.
Available Products: Intravenous and oral NAC are
available as both a 10% and 20% solution. A 10mL
ampoule of NAC 10% contains 100 mg/mL i.e. 1g of NAC
total. A 10mL ampoule of NAC 20% contains 200 mg/mL
i.e. 2g of NAC in total.
Adult Dose - Intravenous Infusion: Administer a
loading dose of 150 mg/kg body weight in 200 mLs of 5%
dextrose by slow intravenous (IV) infusion over 15
minutes. Then administer 50 mg/kg by IV infusion in
500mLs of 5% dextrose over 4 hours followed by 100
mg/kg in 1 litre of 5% dextrose over the next 16
hours. If necessary, NAC can be administered in saline
although its stability in saline is thought to be less
than 24 hours.
At the end of antidote treatment a blood sample should
be taken for determination of INR, plasma creatinine
concentration and blood gases. If they are normal and
the patient is asymptomatic the patient may be
discharged. If INR and/or plasma creatinine are raised
then the patient requires further monitoring and more
acetylcysteine should be given at a rate of 150 mg/kg
over 24 hours.
Adult Dose - Oral and Nasogastric Administration:
Administer a loading dose of 140 mg/kg body weight.
Four hours after administration of the loading dose,
initiate a maintenance dose of 70 mg/kg administered
every four hours for 17 doses. The NAC solution
should be diluted to a 5% solution in soda pop, juice
or water prior to oral and nasogastric administration.
Oral NAC should be administered as a cold solution
through a covered container and straw in order to
increase palatability. It is important not to delay in
treating a patient with a paracetamol overdose.
Although NAC is useful up to 72 hours post ingestion,
its efficacy decreases greatly if started more than 8
hours post ingestion (Makin et al., 1994, Prescott
1983).
Adverse effects of IV NAC: IV NAC may cause
discomfort along the vein of administration,
erythematous or urticarial rashes, nausea, vomiting,
diarrhoea, headache, and tinnitus. For mild allergic
reactions administer antihistamines and continue
treatment.
Anaphylactoid reactions, including bronchospasm
(particularly in asthmatics) and hypotension have been
reported in sensitive patients or if the initial
infusion is given more rapidly than recommended. In
such cases, stop the infusion immediately and give an
antihistamine such as diphenhydramine or
chlorpheniramine, adrenaline, corticosteroids, and
bronchodilators as necessary. In some centres, if it
is less than 8 hours after exposure, oral methionine
(see below) is administered if activated charcoal has
not been given. If more than 8 hours has passed since
the overdose, these centres recommend resumption of
the NAC infusion at the lowest rate (100mg/kg over 16
hours) with concurrent antihistamine and steroid
treatment.
Adverse Effects of Oral and Nasogastric NAC: The
most common adverse effect following administration of
oral NAC is vomiting. This is due to the noxious
odour and taste of the product. Efforts to enhance
palatability, as described above, should be taken. If
a patient vomits the NAC dose within one hour of
administration, the dose should be administered again.
Efforts to prevent further episodes of vomiting should
be taken. Antiemetics such as metoclopramide or
ondansetron can be used. The anti-emetic dose of
metoclopramide is 1 mg/kg. This can be mixed in 50 mL
of 0.9% sodium chloride solution or 5% dextrose
solution. It should then be administered
intravenously over 30 minutes. Ondansetron, 150
œg/kg, should be mixed in 50 mL of 0.9% sodium
chloride solution or 50 mL of 5% dextrose solution.
If emesis has occurred following oral NAC
administration, a nasogastric or duodenal tube can be
placed. If these interventions are not effective in
preventing vomiting, intravenous administration of NAC
should be initiated.
Urticaria has also been observed after oral and
nasogastric administration.
NAC interference with paracetamol measurement:
Laboratories using enzymatic kits for paracetamol
measurements may find a reduction in the true
paracetamol level when NAC has been administered. This
applies ONLY when the analytic method has been
modified for use on certain types of clinical
analysers. When the kits are used manually, according
to the manufacturer's instructions there is no
interference.
Methionine (please also see
Antidotes for poisoning by Paracetamol):
Some centres use methionine rather than NAC if the
patient presents within 8 hours of ingestion, is
conscious, not vomiting and if activated charcoal has
not been given.
Adult Dose: The adult dose is 2.5g orally every 4
hours for 4 doses (10g total). Children over 6 years
of age should be treated with the adult dose.
10.5.2 Children
N-acetylcysteine (NAC) (please also see
Antidotes for poisoning by Paracetamol):
Paediatric Dose - Intravenous Infusion: In children
who weigh greater than 20kg, administer an NAC loading
dose of 150 mg/kg in 100 mLs of 5% dextrose over 15
minutes. Then administer 50 mg/kg in 250mLs of 5%
dextrose over 4 hours followed by 100 mg/kg in 500mLs
of 5% dextrose over the next 16 hours. For children
who weigh less than 20 kg, administer the NAC doses
listed for children greater than 6 years old and
adjust the infusion volumes based on the daily fluid
requirements of the child by weight.
Paediatric Dose - Oral and Nasogastric
Administration: Administer a loading dose of 140
mg/kg body weight. Four hours after administration of
the loading dose, initiate a maintenance dose of 70
mg/kg administered every four hours for 17 doses. The
NAC solution should be diluted to a 5% solution in
soda pop, juice or water prior to oral and nasogastric
administration. Oral NAC should be administered as a
cold solution through a covered container and straw in
order to increase palatability.
Methionine
Paediatric Dose: Children over 6 years of age should
be treated with the adult dose. In children less than
6 years of age, the dose is 1 g administered orally
every 4 hours for 4 doses (4g total).
10.6 Management discussion
Activated charcoal does not significantly interfere
with the absorption of NAC from the gastrointestinal tract.
One complication associated with the concurrent
administration of NAC and charcoal is an increased risk for
vomiting.
Criteria for Liver Transplant: If the patient has any of the
following: evidence of acidosis, coagulopathy that does not
respond to therapy or that persists as transaminases
decrease, hypoglycaemia, renal failure, hypotension (mean
arterial pressure less than 60mmHg) or encephalopathy, as
they are all possible indications of irreversible hepatic
toxicity and potential multi-system failure.
Some centres will administer both oral or intravenous NAC in
patients who present after 72 hours, including those
patients who present with signs of hepatic toxicity.
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
12. Additional information
12.1 Specific preventive measures
12.2 Other
For further information please also see
Antidotes for poisoning by Paracetamol
13. REFERENCES
Budavari S ed. (1996) The Merck Index: an encyclopedia of
chemicals, drugs and biologicals, 12th ed. Rahway, New Jersey,
Merck and Co., Inc.
Makin A.J, Wendon J, Williams R. (1994) Management of severe
cases of paracetamol overdosage. Br J of Hosp Med, 52(5):
210-3
Miller R.P., Roberts R.J., Fischer L.J. (1976) Acetaminophen
kinetics in neonates, children and adults. Clin Pharm & Ther,
19:284-94.
Penna A., Buchanan N. (1991) Paracetamol poisoning in children and
hepatotoxicity. Br J Clin Pharmac, 32: 143-149
Prescott L.F. (1983) Paracetamol Overdosage, Pharmacological
Considerations and Clinical Management. Drugs 25: 290-314
Rumack B.H. (1985) Acetaminophen: Acute overdose Toxicity in
children. Drug Intell Clin Pharm. 19: 911-2
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESS(ES)
Author: Medical Toxicology Unit,
Guy's and St Thomas' Trust
Avonley Road, London SE14 5ER, UK
Date: November, 1996
Review: As for author. 1996
Peer review: INTOX meeting, March 1998, London, UK
(Members of group: Drs G. Allridge, L.
Lubomovir, R. Turk, C. Alonso, S. de Ben, K.
Hartigan-Go, N. Bates)
Editor: Dr M.Ruse (September, 1998)