Pharmacokinetics in children

Bumetanide is eliminated both renally and non-renally; on average, 34% of the dose is found unchanged in the urine (Marshall et al.).
The clearance increases with increasing postnatal age, from 0.2-1.0 ml/min/kg in premature neonates to 2.7±1.9 ml/min/kg in infants [Lopez et al., Sullivan et al.].
Average elimination half-life in premature infants: 6-7 hours (range 4-19 hours).
The study by Sullivan et al. shows that the elimination half-life decreases exponentially in the first month of life, principally because of the increased clearance. Average elimination half-life in infants: 2.3 ± 1.4 hours

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

Diuretics for oedema
Intravenous 1 month up to 18 years 0.01 - 0.1 mg/kg/dose 1-4 times daily. Max: 0.2mg/kg/dose, but not exceeding 10 mg/day. Inject over 1-2 minutes Oral 1 month up to 18 years 0.01 - 0.1 mg/kg/dose 1-4 times daily. Max: 0.2mg/kg/dose, but not exceeding 10 mg/day.

Renal impaiment in children > 3 months

Adjustment in renal impairment as specified:

GFR 50-80 ml/min/1.73 m2

Adjustment not necessary.

GFR 30-50 ml/min/1.73 m2

Adjustment not necessary.

GFR 10-30 ml/min/1.73 m2

Adjustment not necessary.

GFR < 10 ml/min/1.73 m2

No generalized dose recommendations are given

Clinical consequences

In reduced renal function, bumetanide often has to be given at a higher dosage in order to achieve sufficient diuretic effect.

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

At higher dosages and in long-term use, there can be hearing damage and electrolyte imbalances, particularly hypokalaemia and hypomagnesaemia. Extra caution is needed when other ototoxic drugs are being used concomitantly (including aminoglycosides, indomethacin, amphotericin B). In children in particular, dehydration can result in thromboembolic processes or collapse. In premature infants, elevations of the serum creatinine concentration, total bilirubin and direct bilirubin have also been observed.

 

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

Caution is needed in neonates with hyperbilirubinaemia. Because of the longer half-life in premature infants, the dosage given each time must not be exceeded. Also given the lack of any dose-effect relationship for dosages of above 0.2 mg/kg, higher dosages are not recommended: At dosages of higher than 0.2 mg/kg, only a very slight increase in diuresis is seen, but the risk of electrolyte problems and ototoxicity increases. 

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

• CARDIOVASCULAR SYSTEM
• DIURETICS

HIGH-CEILING DIURETICS

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

Sulfonamides, plain
	Furosemide Related Medicines Menu">	C03CA01
	Torasemid Related Medicines Menu">	C03CA04

Aryloxyacetic acid derivatives
	Etacrynsäure Related Medicines Menu">	C03CC01

References

1. Oliveros M, et al, The use of bumetanide for oliguric acute renal failure in preterm infants, Pediatr Crit Care Med, 2010, Jul 9
2. Marshall JD, et al, Pharmacokinetics and pharmacodynamics of bumetanide in critically ill pediatric patients, J Clin Pharmacol, 1998, Nov;38(11), 994-1002
3. Lopez-Samblas AM, et al, The pharmacokinetics of bumetanide in the newborn infant., Biol Neonate, 1997, 72(5), 265-72
4. Sullivan JE, et al, Dose-ranging evaluation of bumetanide pharmacodynamics in critically ill infants, Clin Pharmacol Ther, 1996, Oct;60(4), 424-34
5. Sullivan JE, et al, Analysis of the variability in the pharmacokinetics and pharmacodynamics of bumetanide in critically ill infants, Clin Pharmacol Ther, 1996, Oct;60(4), 414-23
6. Sullivan JE, et al, Pharmacokinetics of bumetanide in critically ill infants, Clin Pharmacol Ther, 1996, Oct;60(4), 405-13
7. Walker PC, et al, The bilirubin-displacing capacity of bumetanide in critically ill neonates, Dev Pharmacol Ther, 1988, 11(5), 265-72
8. Ward OC, et al, Bumetanide in heart failure in infancy, Arch Dis Child, 1977, Nov;52(11), 877-82

Changes

Therapeutic Drug Monitoring

Overdose