Pharmacokinetics in children

Children (n=78, 2-17 yrs) were given oral doses of up to 30 mg/day. Cmax: 44.3 ng/ml. Trend towards shorter t½ for children compared to adults.
Observed effective levels for tics: 1-4 ng/ml (SPC for Haldol).

 

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

Schizophrenia (psychoses), behavioural disorder, autism and tics

Oral 6 years up to 12 years Initial dose: 0.01 - 0.025 mg/kg/day in 1 - 2 doses. Maintenance dose: The starting dose (daily dose) can be increased weekly depending on the effect and the side effects by 0.25-0.5 mg to achieve the desired result. This is generally achieved with dosages of between 0.05 - 0.075 mg/kg/day in 1 - 2 doses. Max: 0.15 mg/kg/day. The maximum dose of 0.15 mg/kg/day can only be applied where necessary in cases of psychosis

Delirium in critically ill children

Intravenous 3.5 up to 10 kg Initial dose: 0.05 mg/dose The starting dose can be repeated twice with an interval of one hour. Then re-evaluate the effect and side effects.. Maintenance dose: 0.01 mg/kg/day in 1 - 3 doses. Increase further depending on the clinical response: “start low and go slow”. . Run in slowly, over at least 30 minutes When switching from intravenous to oral, higher doses may be needed (up to as much as twice the IV dose) because of a large first-pass effect. 10 up to 15 kg Initial dose: 0.15 mg/dose The starting dose can be repeated twice with an interval of one hour. Then re-evaluate the effect and side effects.. Maintenance dose: 0.025 mg/kg/day in 1 - 3 doses. Increase further depending on the clinical response: “start low and go slow”.. Run in slowly, over at least 30 minutes When switching from intravenous to oral, higher doses may be needed (up to as much as twice the IV dose) because of a large first-pass effect. ≥ 15 kg Initial dose: 0.25 mg/dose The starting dose can be repeated twice with an interval of one hour. Then re-evaluate the effect and side effects.. Maintenance dose: 0.05 mg/kg/day in 1 - 3 doses. Increase further depending on the clinical response: “start low and go slow”.. Run in slowly, over at least 30 minutes When switching from intravenous to oral, higher doses may be needed (up to as much as twice the IV dose) because of a large first-pass effect. Oral < 45 kg Initial dose: 0.01 - 0.02 mg/kg/dose The loading dose can be repeated twice at intervals of one hour.. Then re-evaluate the effect and side effects. An initial therapeutic response must be sought during the first 24 hours. How long and how well this first response lasts determines the next step.. Maintenance dose:  The cumulative dose for the first 24 hours should be given in 2-3 doses. Increase further if necessary depending on the effect and the side effects by 0.25-0.5 mg to achieve the desired result. This is generally achieved with dosages of between  0.01 - 0.08 mg/kg/day in 2 doses. ≥ 45 kg Initial dose: 0.5 - 1 mg/dose The loading dose can be repeated twice at intervals of one hour.. Then re-evaluate effect and side efects. An initial therapeutic response must be sought during the first 24 hours. How long and how well this first response lasts determines the next step.. Maintenance dose: The cumulative dose for the first 24 hours should be given in 2-3 doses. Increase further if necessary depending on the effect and the side effects by 0.25-0.5 mg to achieve the desired result. This is generally achieved with dosages of between 0.01 - 0.08 mg/kg/day in 2 doses. Max: 6 mg/day.

Intervention medication for acute psychotic crises

Intramuscular 12 years up to 18 years [10] 2.5 - 5 mg/dose, once only. If oral medication is refused or does not have the desired effect, intramuscular administration can be considered. Haloperidol should be prescribed by a child and youth psychiatry specialist. The dosage should be set individually and the lowest possible dose should be used.   12 years up to 18 years 2.5 - 5 mg/dose, once only. If oral medication is refused or does not have the desired effect, intramuscular administration can be considered. Haloperidol should be prescribed by a child and youth psychiatry specialist. The dosage should be set individually and the lowest possible dose should be used.   12 years up to 18 years 2.5 - 5 mg/dose, once only. If oral medication is refused or does not have the desired effect, intramuscular administration can be considered. Haloperidol should be prescribed by a child and youth psychiatry specialist. The dosage should be set individually and the lowest possible dose should be used.

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 in children

Drowsiness. The rhabdomyolysis and the associated renal insufficiency are usually life-threatening. A number of cases of rhabdomyolysis in children have been described in the literature. As with other antipsychotics, you should be aware of the occurrence of what is known as ‘malignant neuroleptic syndrome’. In parenteral administration, some cases have been reported of sudden unexplained death, extension of the QTc interval and ventricular arrhythmias, especially at high doses and in patients predisposed to these symptoms.

 

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

Contra-indications in children

Extended QTc interval.

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

The maintenance dose for the indication ‘delirium’ should, according to the “start low and go slow” principle, be built up slowly on the basis of the clinical picture and the response to the medication. However, it should be noted that a number of extra interventions are often required within the first 24 hours. This is because paediatric delirium is an acute paediatric psychiatric crisis situation that often requires rapid and successful intervention. Phasing out should also take place slowly after the clinical situation has been stable for 48 hours. The total daily dosage can be phased out over a maximum of about one week. When converting from intravenous to oral administration, high doses (up to double the IV dose) may be required (due to a first-pass effect) and divided into 2-3 doses/day.

As with other antipsychotics, when using haloperidol you should be aware of the occurrence of what is known as ‘malignant neuroleptic syndrome’, in which hyperthermia, extreme muscle rigidity and autonomic instability are key.

It is sensible to consider new or increased feelings of unease or restlessness in the patient as potentially being akathisia (painful spasms) before increasing the dose.

If severe side effects occur of if there is no effect, it is possible that the metabolization of the drug may be different. CYP2D6 can determine the variation in response. Genotyping can be considered.

The safety data available for children and adolescents indicate a risk of developing extrapyramidal symptoms including tardive dyskinesia and sedation. [SmPC Halodl]

 

Interactions

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

Phenothiazines with aliphatic side-chain
	Levomepromazin Related Medicines Menu">	N05AA02

Butyrophenone derivatives
	Pipamperone (as the hydrochloride) Related Medicines Menu">	N05AD05

Indole derivatives
	Lurasidon Related Medicines Menu">	N05AE05
	Ziprasidon Related Medicines Menu">	N05AE04

Diphenylbutylpiperidine derivatives
	Pimozide Related Medicines Menu">	N05AG02

Diazepines, oxazepines, thiazepines and oxepines
	Clozapine Related Medicines Menu">	N05AH02
	Olanzapine Related Medicines Menu">	N05AH03
	Quetiapine Related Medicines Menu">	N05AH04

Lithium
	Lithium Related Medicines Menu">	N05AN01

Other antipsychotics
	Aripiprazole Related Medicines Menu">	N05AX12
	Paliperidon Related Medicines Menu">	N05AX13
	Risperidone Related Medicines Menu">	N05AX08

References

1. Anderson LT et al., The effects of haloperidol on discrimination learning and behavioral symptoms in autistic children, J Autism Dev Disord, 1989, 19, 227-39
2. Sikich L, et al, A pilot study of risperidone, olanzapine, and haloperidol in psychotic youth: a double-blind, randomized, 8-week trial., Neuropsychopharmacology, 2004, 29(1), 133-145.
3. Brown RL, et al, The use of haloperidol in the agitated, critically ill pediatric patient with burns, J Burn Care Rehabil., 1996, 17, 34-8
4. Campbell M et al, Neuroleptic-related dyskinesias in autistic children: a prospective, longitudinal study., J Am Acad Child Adolesc Psychiatry., 1997, 36, 835-43
5. Schieveld JN, et al, Delirium in critically ill children in a paediatric intensive care unit., Ned Tijdschr Geneeskd., 2006, 15, 1545-8
6. Spencer EK, et al, Children with schizophrenia: diagnosis, phenomenology, and pharmacotherapy., Schizophr Bull., 1994, 20, 713-25
7. Valk, J.A. van der, et al, Het pediatrisch delier: een ernstige aandoening bij kritisch zieke kinderen, Psyfar, 2008
8. Hatherill S et al., Delirium among children and adolescents in an urban sub-Saharan African setting., J Psychosom Res., 2010, Aug;69(2), 187-92
9. Janssen-Cilag B.V., SPC Haldol druppels (RVG 03186) 24-11-2017, www.geneesmiddeleninformatiebank.nl
10. Kenniscentrum Kind,- en Jeugdpsychiatrie, Ingrijpmedicatie protocol 2016. , www.kenniscentrum/kjp.nl
11. Schieveld JNM et al. , Multidisciplinaire richtlijn pediatrisch delier. , 2014
12. JANSSEN-CILAG, SmPC HALDOL®-Janssen 1 mg, Tabletten (6762187.00.00), 04/2017
13. Gerlach M, Mehler-Wex C, Walitza S, Warnke A, Wewetzer C. , Neuro-/Psychopharmaka im Kindes- und Jugendalter: Grundlagen und Therapie. , Springer-Verlag Berlin Heidelberg , 2016, 3.Auflage, 230
14. Gerlach M, Mehler-Wex C, Walitza S, Warnke A, Wewetzer C., Neuro-/Psychopharmaka im Kindes- und Jugendalter: Grundlagen und Therapie., Springer-Verlag Berlin Heidelberg, 2016, 3.Auflage, 230
15. Schieveld JNM et al., Multidisciplinaire richtlijn pediatrisch delier., 2014
16. Kenniscentrum Kind,- en Jeugdpsychiatrie, Ingrijpmedicatie protocol 2016., www.kenniscentrum/kjp.nl

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