PARACETAMOL-Intravenous

Perfalgan

Prepared by Dr Mariam Buksh, Amy Chan, Brenda Hughes &
Elizabeth Oliphant
Reviewed by Dr Andrew Liley, Clinical Leader, Acute Pain Service, Starship Children’s Health, Auckland City Hospital

February 2011

Dose and Administration

Postmenstrual Age (weeks)	Dose (mg/kg/dose)	Interval (hours)	Maximum Dose
<32/40	7.5	8	22.5 mg/kg/day
≥ 32/40	7.5	6	30 mg/kg/day

Indications

Analgesia

Intravenous Paracetamol use should be reviewed daily on ward rounds.

It is recommended to use a suitable oral or rectal analgesic treatment as soon as practicable.

Contraindications

known sensitivity to paracetamol
Severe hepatocellular insufficiency
When oral or rectal route available

Precautions

Use in the 1st 24-hours after birth (see "Special Considerations").
Moderate or severe pain where a more potent analgesic may be more appropriate
Use in extremely preterm infants
Impaired hepatic or kidney function
Unconjugated hyperbilirubinaemia (clearance is reduced)
G6PD deficiency (may lead to haemolytic anaemia)
Hypovolaemia

Clinical Pharmacology

Paracetamol has analgesic and antipyretic actions but only weak anti-inflammatory properties. It inhibits prostaglandin biosynthesis in conditions associated with low levels of cellular peroxides (pain, fever).

Due to metabolic immaturity, neonatal clearance of paracetamol is different from adults. Sulphate conjugation is well developed in a neonate and is the major metabolic pathway for paracetamol clearance. Glucuronidation clearance is not well developed and plays a minor role in paracetamol clearance in neonates. With maturation these clearance pathways for paracetamol change. The usual adult ratio of 2:1 glucuronide to sulphate conjugates of paracetamol is achieved by 12 years of age.

The enzyme systems P450 CYP2E1, 1A2, 3A4 are responsible for forming paracetamol toxic metabolites. Despite a low activity of P450 CYP 2E1 in neonates, toxic metabolites can still be formed.

In neonates, the half life of intravenous paracetamol is approximately 3.5 hours.

Possible Adverse Effects

Pain at injection site
Hypotonia
Nausea and vomiting
Fever

Special Considerations

Clinical experience in neonates, especially those preterm, is limited.
Caution in the 1st 24 hours for treatment of "pain" related to birth. Infants who are unsettled should be assessed clinically and not assumed to be in pain secondary to birth.