Pharmacokinetics in children

There are only a few studies on the pharmacokinetics of coagulation products in children. Some studies have shown that the half-life of coagulation factor concentrate in young children may be two to four hours shorter than in adult haemophilia patients (18-24 hours). This is probably due to the difference in plasma volume and body composition, which affects clearance and shortens the half-life.

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

MILD BLEEDING (incipient haemarthrosis, nasal and gingival bleeding, haematuria)
Intravenous Term neonate [1] 30 IU/kg/dose, once only. Initial target plasma concentration: 0.3 IU/ml 1 month up to 18 years [1] 30 IU/kg/dose, once only. Initial target plasma concentration: 0.3 IU/ml

SEVERE BLEEDING (severe joint bleeding with mobility restrictions, muscular bleeding in the upper arm and forearm, calf and iliopsoas muscle and severe trauma without manifest bleeding)

Intravenous Term neonate [1] Initial dose: 50 IU/kg/dose, once only. Maintenance dose: 25 IU/kg/day in 1 dose Initial target plasma concentration: 0.5 IU/ml Target plasma concentration for intermittent administration: > 0.25 IU/ml 1 month up to 18 years [1] Initial dose: 50 IU/kg/dose, once only. Maintenance dose: 25 IU/kg/day in 1 dose Initial target plasma concentration: 0.5 IU/ml Target plasma concentration for intermittent administration: > 0.25 IU/ml

LIFE-THREATENING BLEEDING (cranial trauma, bleeding in the digestive tract, abdominal trauma, bleeding that threatens the respiratory tract)

Intravenous Term neonate [1] Initial dose: 100 IU/kg/dose, once only. Maintenance dose: 50 IU/kg/day in 1 dose Initial target plasma concentration: 1.0 IU/ml Target plasma concentration for intermittent administration: > 0.5 IU/ml 1 month up to 18 years [1] Initial dose: 100 IU/kg/dose, once only. Maintenance dose: 50 IU/kg/day in 1 dose Initial target plasma concentration: 1.0 IU/ml Target plasma concentration for intermittent administration: > 0.5 IU/ml

MILD CRANIAL TRAUMA (fall from < 50 cm height, light blow to the head)
Intravenous Term neonate [1] 100 IU/kg/dose, once only. Initial target plasma concentration: 1.0 IU/ml 1 month up to 18 years [1] 100 IU/kg/dose, once only. Initial target plasma concentration: 1.0 IU/ml

MODERATELY SEVERE CRANIAL TRAUMA (fall from > 50 cm height/step, hard blow to the head)

Intravenous Term neonate [1] Initial dose: 100 IU/kg/dose, once only. Maintenance dose: 50 IU/kg/day in 1 dose Initial target plasma concentration: 1.0 IU/ml Target plasma concentration for intermittent administration: 0.5-1.0 IU/ml (2-3 days) 1 month up to 18 years [1] Initial dose: 100 IU/kg/dose, once only. Maintenance dose: 50 IU/kg/day in 1 dose Initial target plasma concentration: 1.0 IU/ml Target plasma concentration for intermittent administration: 0.5-1.0 IU/ml (2-3 days)

SEVERE CRANIAL TRAUMA (concussion or brain contusion)

Intravenous Term neonate [1] Initial dose: 100 IU/kg/dose, once only. Maintenance dose: 50 IU/kg/day in 1 dose Initial target plasma concentration: 1.0 IU/ml Target plasma concentration for intermittent administration: 0.5-1.0 IU/ml (3-10 days) 1 month up to 18 years [1] Initial dose: 100 IU/kg/dose, once only. Maintenance dose: 50 IU/kg/day in 1 dose Initial target plasma concentration: 1.0 IU/ml Target plasma concentration for intermittent administration: 0.5-1.0 IU/ml (3-10 days)

INTRACRANIAL BLEEDING

Intravenous Term neonate Initial dose: 100 IU/kg/dose, once only. Maintenance dose: 50 IU/kg/day in 1 dose Initial target plasma concentration: 1.0 IU/ml Target plasma concentration for intermittent administration: 0.5-1.0 IU/ml (10 days or more) 1 month up to 18 years Initial dose: 100 IU/kg/dose, once only. Maintenance dose: 50 IU/kg/day in 1 dose Initial target plasma concentration: 1.0 IU/ml Target plasma concentration for intermittent administration: 0.5-1.0 IU/ml (10 days or more)

Substitution treatment in procedures in moderately severe to severe haemophilia

Intravenous Term neonate [1] Initial dose: 100 IU/kg/dose, once only. Maintenance dose: first maintenance dose 24 hours after initial dose 50 IU/kg/day in 1 dose Depending on the trough levels. Target values: Day 1: 0.8-1.0 IU/ml Days 2-5: 0.5-0.8 IU/ml Day > 6: 0.3-0.5 IU/ml 1 month up to 18 years [1] Initial dose: 100 IU/kg/dose, once only. Maintenance dose: first maintenance dose 24 hours after initial dose 50 IU/kg/day in 1 dose Depending on the trough levels. Target values: Day 1: 0.8-1.0 IU/ml Days 2-5: 0.5-0.8 IU/ml Day > 6: 0.3-0.5 IU/ml

Prophylaxis for bleeding
Intravenous Term neonate [1] 30 - 50 IU/kg/dose Twice a week. 1 month up to 18 years [1] 30 - 50 IU/kg/dose Twice a week.

Renal impaiment in children > 3 months

No information available on dose adjustment in renal impairment.

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

Side effects

No information is present at this moment.

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

No information available on specific warnings and precautions in children.

Interactions

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

• BLOOD AND BLOOD FORMING ORGANS
• ANTIHEMORRHAGICS

VITAMIN K AND OTHER HEMOSTATICS

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

Vitamin K
	Phytomenadione (vitamin K) Related Medicines Menu">	B02BA01

Blood coagulation factors
	Factor VIII Related Medicines Menu">	B02BD02

Blood coagulation factors
	Factor VIII Related Medicines Menu">	B02BD02

Reference

1. Nederlandse Vereniging van Hemofiliebehandelaars (NVHB)., Richtlijn Diagnostiek en behandeling van hemofilie en aanverwante hemostasestoornissen, 2009, 29-30; 59

Changes

Therapeutic Drug Monitoring

Overdose