Paracetamol

Registered South African indications:

• Short-term treatment of pain - mild to moderate (e.g. following minor surgery)
• Short-term treatment of fever when the oral route is unsuitable

Contraindications

South African recommendations

• Hypersensitivity to paracetamol or to paracetamol hydrochloride (pro-drug of paracetamol) or to any of the excipients
• Cases of severe hepatocellular insufficiency
• Decompensated active liver disease
• Alcoholic hepatitis (1g/100ml inf)
• Children weighing less than 33kg (approximately 11 years old) as safety and efficacy have not been established (1g/100ml inf)

Recommendations in other jurisdictions

• Patients with hypersensitivity to paracetamol, propacetamol hydrochloride (product of paracetamol) or to any of the excipients
• Cases of severe hepatocellular insufficiency

Cautions

• Pregnancy
• Renal impairment
• Mild to moderate hepatic impairment
• Hepatocellular insufficiency
• Chronic alcoholism
• Chronic malnutrition (low glutathione reserves)  
• Dehydration

Forms avail. in SA and covered in this monograph: inj, inf

Dosages below include:

• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

South African registered indications and dosages

Short-term treatment (not exceeding 24hrs) of pain - mild to moderate
- e.g. after dental procedures and minor orthopaedic procedures
Short-term treatment of fever when the oral route is unsuitable

>33kg-≤50kg

• IV: 15mg/kg, up to 6hrly as a 15min infusion; Minimum interval between each admin.: 4hrs; Max: 60mg/kg/24hrs. Do not exceed 3000mg/24hrs

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The minimum interval between each administration must be 4 hours. The maximum daily dose must not exceed 60mg/kg (without exceeding 3g in 24 hours)

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>50kg

• IV: 1000mg, up to 6hrly as a 15min infusion; Minimum interval between each admin.: 4hrs; Max: 4000mg/24hrs

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The minimum interval between each administration must be 4 hours. The maximum daily dose must not exceed 4g in 24 hours

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The maximum daily dose takes into account all the medicines containing paracetamol. The dosage should be calculated on non-oedematous weight

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Method of administration: Paracetamol IV should be administered as a 15 minutes intravenous infusion and should not be mixed with other medicines. Careful monitoring to avoid air embolism is needed, notably at the end of the infusion, especially if a central venous catheter is used for the infusion
Before administration, the product should be visually inspected for any particulate matter and discolouration, e.g. yellowing. It is intended for single-use only. Once opened, the vial should be used immediately Any unused solution should be discarded

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Indications and dosages registered in other jurisdictions

Short-term treatment of pain - moderate
- After surgery, when intravenous administration is clinically justified by an urgent need to treat pain and/or when other routes of administration are not possible
Short-term treatment of fever
- When intravenous administration is clinically justified by an urgent need to treat hyperthermia and/or when other routes of administration are not possible

>33kg-≤50kg

• IV: 15mg/kg, 4-6hrly as a 15min infusion; Max: 60mg/kg/24hrs. Do not exceed 3000mg/24hrs

>50kg and no additional risk factors for hepatotoxicity

• IV: 1000mg, 4-6hrly as a 15min infusion; Max: 4000mg/24hrs 

>50kg with additional risk factors for hepatotoxicity

• IV: 1000mg, 4-6hrly as a 15min infusion; Max: 3000mg/24hrs 

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The minimum interval between each administration must be at least 4 hours; No more than 4 doses to be given in 24 hours

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The maximum daily dose indicated above is for patients that are not receiving other paracetamol containing products and should be adjusted accordingly taking such products into account

Paed. forms avail. in SA and covered in this monograph: inj, inf

Paed. dosages below include:

• South African Standard Treatment Guidelines indications and dosages
• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

South African Standard Treatment Guidelines indications and dosages

• Click here for the Pain Control (Standard Treatment Guidelines And Essential Medicines List For South Africa, Hospital Level, Paediatrics, 2023 Edition)
• Click here for the Anaesthetics (Standard Treatment Guidelines And Essential Medicines List For South Africa, Hospital Level, Paediatrics, 2023 Edition)

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South African registered indications and dosages

Short-term treatment of pain - mild to moderate (e.g. following minor surgery)
Short-term treatment of fever when the oral route is unsuitable

≤10kg

• IV: Up to 7.5mg/kg, for up to 6hrly as a 15min infusion; Minimum interval between each admin.: 4hrs; Max: 30mg/kg/24hrs

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Preterm newborn infants: No safety and efficacy data are available for premature newborn infant

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The maximum daily dose as presented above is for patients that are not receiving other paracetamol containing products and should be adjusted accordingly taking such products into account. Prolonged or frequent use is discouraged. It is recommended that a suitable analgesic oral treatment will be used as soon as this route of administration is possible

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Patients weighing less will require smaller volumes

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The dosage should be calculated on non-oedematous weight. The minimum interval between each administration must be at least 4 hours, up to four times a day

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Paracetamol paediatric 100mg/10ml ampoule is restricted to term newborn infants, infants and toddlers weighing up to 10kg

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Patients weighing 10kg or less: The volume to be administered should be withdrawn from the container and diluted in a 0.9% sodium chloride solution or 5% glucose solution or a combination of both solutions up to one tenth (one volume paracetamol paediatric 100mg/10ml into nine volumes diluent) and administered over 15 minutes

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Paracetamol IV should not be mixed with other medicinal products. Before administration, the product should be visually inspected for any particulate matter and discolouration. It is intended for single-use only. Once opened, the vial should be used immediately. Any unused solution should be discarded

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Risk of medication errors: Take care when prescribing and administering paracetamol IV to avoid dosing errors due to confusion between milligram (mg) and milliliter (ml), which could result in accidental overdose and death. Take care to ensure the proper dose is communicated and dispensed. When writing prescriptions, include both the total dose in mg and the total dose in volume. Take care to ensure the dose is measured and administered accurately

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Indications and dosages registered in other jurisdictions

Short-term treatment of pain - moderate
- After surgery, when intravenous administration is clinically justified by an urgent need to treat pain and/or when other routes of administration are not possible
Short-term treatment of fever
- When intravenous administration is clinically justified by an urgent need to treat hyperthermia and/or when other routes of administration are not possible

≤10kg

• IV: 7.5mg/kg, 4-6hrly administered as an infusion >15min; Max: 30mg/kg/24hrs

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Pre-term newborn infants: No safety and efficacy data are available for pre-term newborn infants

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>10kg-≤33kg

• IV: 15mg/kg, 4-6hrly administered as an infusion >15min; Max: 60mg/kg/24hrs. Do not exceed 2000mg/24hr

>33kg-≤50kg

• IV: 15mg/kg, 4-6hrly administered as an infusion >15min; Max: 60mg/kg/24hrs. Do not exceed 3000mg/24hrs

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The minimum interval between each administration must be at least 4 hours. No more than 4 doses to be given in 24 hours. It is recommended to use an oral analgesic treatment as soon as this route of administration is possible

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For all indications: The maximum daily dose as presented above is for patients that are not receiving other paracetamol containing products and should be adjusted accordingly taking such products into account

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Patients weighing less will require smaller volumes

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Patients weighing 10kg or less:  The volume to be administered should be withdrawn from the bag and could be administered undiluted or diluted (from one to nine volumes diluent) in a 0.9% sodium chloride solution or 5% glucose solution and administered in 15 minutes

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Risk of medication errors: Take care when prescribing and administering paracetamol IV to avoid dosing errors due to confusion between milligram (mg) and milliliter (ml), which could result in accidental overdose and death. Take care to ensure the proper dose is communicated and dispensed. When writing prescriptions, include both the total dose in mg and the total dose in volume

Pregnancy

• Caution
• A large amount of data on pregnant women indicate neither malformative, nor feto/neonatal toxicity. Epidemiological studies on neurodevelopment in children exposed to paracetamol in utero show inconclusive results. If clinically needed, paracetamol can be used during pregnancy however it should be used at the lowest effective dose for the shortest possible time and at the lowest possible frequency

Breastfeeding

• Compatible
• After oral administration, paracetamol is excreted into breast milk in small quantities. No undesirable effects on nursing infants have been reported. Consequently, paracetamol IV may be used in breast-feeding women

Renal Impairment

• Mild: Caution; no dose adjustment recommended
• Moderate to severe: Caution; dose adjustment recommended

GFR (ml/min)	Dose
≥60	No adjustment necessary
30-59	15mg/kg/day; Max: 3g/24hrs
≤29	10mg/kg/day; Max: 2g/24hrs

Hepatic Impairment

South African recommendations

Adult recommendations

• Mild to moderate (chronic or compensated active hepatic disease): Caution; dose adjustment recommended
  Adults weighing less than 50kg, Gilbert’s syndrome (familial hyperbilirubinaemia), chronic alcoholism, chronic malnutrition (low reserves of hepatic glutathione) and dehydration: Caution; dose adjustment recommended
  Max: 60mg/kg/24hrs. Do not exceed 2000mg/24hrs
• Severe: Contraindicated

Paediatric recommendations

• Mild to moderate (chronic or compensated active hepatic disease): Caution; dose adjustment recommended
  Gilbert’s syndrome (familial hyperbilirubinaemia), chronic malnutrition (low reserves of hepatic glutathione) and dehydration: Caution; dose adjustment recommended
  Max: 30mg/kg/24hrs
• Severe: Contraindicated

Recommendations in other jurisdictions

Adult recommendations

• Mild to moderate: Caution; dose adjustment recommended
  Child-Turcotte-Pugh class A and B (those actively consuming alcohol): Max: 2000mg/24hrs (any duration of treatment) 
  Child-Turcotte-Pugh class A (those who are not actively consuming alcohol): Short-term use (≤14 days): Max: 4000mg/24hrs; Long-term use (>14 days): Max: 3000mg/24hrs
  Child-Turcotte-Pugh class B (those who are not actively consuming alcohol):  Short-term use (≤14 days): Max: 3000mg/24hrs; Long-term use (>14 days): Max: 2000mg/24hrs
• Severe: Contraindicated

Paediatric recommendations

• Mild to moderate: Caution; dose adjustment recommended
  Lower limited dose therapy is usually well-tolerated, avoid chronic use
• Severe: Contraindicated

Elderly

• No dose adjustment recommended

Porphyria information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Malaise

Cardiovascular System Disorders

• Hypotension
• Tachycardia

Hepatobiliary Disorders

• Increased hepatic transaminases

Skin and Subcutaneous Tissue Disorders

• Pain and burning sensation at injection site
• Erythema
• Flushing
• Pruritus

Immune, Blood and Lymphatic System Disorders

• Thrombocytopenia
• Leucopenia
• Neutropenia
• Hypersensitivity reactions
  - Skin rash
  - Urticaria
  - Anaphylactic shock

• Probenecid
• Salicylamide
• Enzyme inducing agents
• Oral anticoagulants

None routine. Specific cases may require

• Renal function
• Hepatic function  

Hepatic damage

• Doses higher than those recommended entail the risk of very serious hepatic damage. Clinical signs and symptoms of hepatic damage (including fulminant hepatitis, hepatic failure, cholestatic hepatitis, cytolytic hepatitis) are usually first seen after two days of drug administration with a peak seen usually after 4-6 days. Treatment with antidote should be given as soon as possible

The mechanism of analgesic action has not been fully determined. Paracetamol may act predominantly by inhibiting prostaglandin synthesis in the central nervous system (CNS) and, to a lesser extent, through a peripheral action by blocking pain impulse generation. The peripheral action may also be due to inhibition of prostaglandin synthesis or to inhibition of the synthesis or actions of other substances that sensitise pain receptors to mechanical or chemical stimulation. Paracetamol probably produces antipyresis by acting centrally on the hypothalamic heat regulating centre to produce peripheral vaso-dilation resulting in increased blood flow through the skin, sweating and heat loss. The central action probably involves inhibition of prostaglandin synthesis in the hypothalamus.

Injection (per 100ml) 1g 

• Cetafuse (Actavis)
• Cetagesic IV Paed (Biotech Laboratories)
• Intramol (Equity)
• Paracetamol Biotech (Biotech Laboratories)
• Paracetamol Fresenius (Fresenius Kabi)
• Paraspen IV (Pharmacare)
• Perfalgan (Bristol-Myers Squibb) originator

Injection (per 50ml) 500mg 

• Perfalgan Paediatric (Bristol-Myers Squibb) originator

Also available in the following forms: Syrup, tablet, capsule, suppository and drop.