ADMINISTRATION ROUTES:
PO, NG, IV
ALTERNATIVE NAMES:
Acetadote, Parvolex
ICU INDICATIONS:
- Paracetamol overdose
- Non-paracetamol induced fulminant hepatic failure
Contrast-induced nephropathy is not a pathological entity; acetylcysteine should not be administered to prevent it.
PRESENTATION AND ADMINISTRATION:
PO / NG:
Give IV solution orally
IV:
Acetadote and Parvolex are supplied as sterile solutions in 10 mL vials containing 20% (200 mg/mL) acetylcysteine. Compatible with 5% dextrose. Prepare immediately before use and discard any solution not used within 24 hours.
Note: Section 29 drug when administered orally (requires specific notification to Director-General of Health as unapproved route of administration)
DOSAGE IN ADULTS
Paracetamol Overdose:
Guidelines changed in 2020 to a two stage infusion:
First infusion: 200 mg/kg IV in 500 mL of 5% dextrose over 4 hours
Second Infusion: 100 mg/kg IV in 1000 mL of 5% dextrose over 16 hours
If ongoing infusion is required, continue to repeat the second infusion.
Dose calculation and preparation per weight is shown in the table below:
| First acetylcysteine infusion | Second acetylcysteine infusion | |
|---|---|---|
| 200 mg/kg over 4 hours in 500 mL 5% dextrose | 100 mg/kg over 16 hours in 1000 mL 5% dextrose | |
| Weight (kg) | Dose acetylcysteine (gm) = 0.2 x body weight (kg) | Dose acetylcysteine (gm) = 0.1 x body weight (kg) |
| 50 | 10 gm. Add 50 mL 20% acetylcysteine to 450 mL 5% dextrose | 5 gm. Add 25 mL 20% acetylcysteine to 975 mL 5% dextrose |
| 60 | 12 gm. Add 60 mL 20% acetylcysteine to 440 mL 5% dextrose | 6 gm. Add 30 mL 20% acetylcysteine to 970 mL 5% dextrose |
| 70 | 14 gm. Add 70 mL 20% acetylcysteine to 430 mL 5% dextrose | 7 gm. Add 35 mL 20% acetylcysteine to 965 mL 5% dextrose |
| 80 | 16 gm. Add 80 mL 20% acetylcysteine to 420 mL 5% dextrose | 8 gm. Add 40 mL 20% acetylcysteine to 960 mL 5% dextrose |
| 90 | 18 gm. Add 90 mL 20% acetylcysteine to 410 mL 5% dextrose | 9 gm. Add 45 mL 20% acetylcysteine to 955 mL 5% dextrose |
| 100 | 20 gm. Add 100 mL 20% acetylcysteine to 400 mL 5% dextrose | 10 gm. Add 50 mL 20% acetylcysteine to 950 mL 5% dextrose |
| 110* | 22 gm. Add 110 mL 20% acetylcysteine to 390 mL 5% dextrose | 11 gm. Add 55 mL 20% acetylcysteine to 945 mL 5% dextrose |
*all patients weighing > 110kg should be dosed according to a bodyweight of 110 kg
Run first infusion at 125 mL/hour then second infusion at 62.5 mL/hour
DOSAGE IN PAEDIATRICS (less than 14 years of age)
Paracetamol Overdose
First infusion: 200 mg/kg IV in 7 mL/kg (up to 500 mL) of 0.9% saline over 4 hours
Second infusion: 100 mg/kg IV in 14 mL/kg (up to 1000 mL) of 0.9% saline over 16 hours
ADDITIONAL DOSAGE NOTES
Where there has been a massive overdose with initial paracetamol concentrations more than double the nomogram line, the second infusion should be 200 mg/kg and toxicology advice should be obtained. Weight-based dosing is the same for both adults & children; the volume of diluent fluid differs for children. Saline is used as the diluent for children due to the risk of hyponatraemia with 5% dextrose.
DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY
No dose adjustment is required.
CLINICAL PHARMACOLOGY:
Paracetamol Overdose
Acetylcysteine likely protects the liver by maintaining or restoring the glutathione levels, or by acting as an alternate substrate for conjugation with, and thus detoxification of, the reactive metabolite.
CONTRAINDICATIONS:
- Hypersensitivity or previous anaphylactoid reactions to acetylcysteine
WARNINGS:
Serious anaphylactoid reactions, including death in a patient with asthma, have been reported in patients administered acetylcysteine intravenously.
PRECAUTIONS:
General: The total volume administered should be adjusted for patients less than 40 kg and for those requiring fluid restriction (use DOSAGE IN PAEDIATRICS regimen).
Laboratory Tests: No tests are required in addition to routine ICU blood tests
Drug/Laboratory Test Interactions: None reported
IMPORTANT DRUG INTERACTIONS IN ICU:
None known
ADVERSE REACTIONS:
Body as a Whole:
Urticaria, vasodilatation, rash and itch
Cardiovascular System:
Hypotension
Digestive System:
Dyspepsia, nausea, vomiting
Nervous System:
Abnormal thinking (dysphoria), gait disturbances
Respiratory System:
Bronchospasm, coughing, dyspnoea
Skin & Appendages:
Angioedema, facial erythema, palmar erythema, pruritus, pruritus, rash, sweating
SEE APPENDIX 3 FOR PARACETAMOL POISONING TREATMENT NOMOGRAM