Pharmacokinetics in children

Risperidone is converted by CYP2D6 into inter alia 9-hydroxyrisperidone, which retains the same pharmacological activity as risperidone. Risperidone and 9-hydroxyrisperidone together form the active antipsychotic fraction.

The pharmacokinetics of risperidone, 9-hydroxyrisperidone and the active antipsychotic fraction in children (4 to 15 years) are similar to those in adults. After oral administration to psychotic patients, risperidone is eliminated with a half-life of approximately 3 hours. The elimination half-lives of 9-hydroxyrisperidone and of the active antipsychotic fraction are 24 hours.

The tablet and orodispersible tablet are bioequivalent.

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

Paediatric delirium in critically ill children

Oral < 45 kg Initial dose: 0.02 mg/kg/dose, once only. 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 - 0.08 mg/kg/day in 2 doses. Max: 4 mg/day. Directions for administration: Risperidone solution should not be taken together with tea. ≥ 45 kg Initial dose: 0.5 - 1 mg/dose, once only. 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 - 0.08 mg/kg/day in 2 doses. Max: 6 mg/day. Directions for administration: Risperidone solution should not be taken together with tea.

Psychosis/schizophrenia, bipolar disorder (mania)

Oral 5 years up to 18 years Initial dose: 0.01 - 0.02 mg/kg/day in 1 dose In the evening. Maintenance dose: The dosage should be titrated slowly depending on the effect and the side effects (e.g. in steps of 0.25-0.5 mg once daily, no more often than once every other day) 0.01 - 0.08 mg/kg/day in 2 doses. Max: 3 mg/day. Directions for administration: Risperidone solution should not be taken together with tea. Higher doses may be needed in rare cases.   The medicine should be phased out gradually when it is being discontinued. 5 years up to 18 years [9] [20] [21] [22] [23] Initial dose: 0.01 - 0.02 mg/kg/day in 1 dose In the evening. Maintenance dose: The dosage should be titrated slowly depending on the effect and the side effects (e.g. in steps of 0.25-0.5 mg once daily, no more often than once every other day) 0.01 - 0.08 mg/kg/day in 2 doses. Max: 3 mg/day. Directions for administration: Risperidone solution should not be taken together with tea. Higher doses may be needed in rare cases.   The medicine should be phased out gradually when it is being discontinued.

Renal impaiment in children > 3 months

Halve the dose if there are severe hepatic and renal function disorders. Titrate upwards more slowly in such cases as well.

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

Sleepiness/sedation, increased appetite, weight gain, fatigue, headaches, vomiting, upper respiratory tract infection, nasal congestion, abdominal pain, dizziness, coughing, fever, tremors, diarrhoea, enuresis, increased prolactin levels, galactorrhoea, extrapyramidal symptoms and withdrawal dyskinesia. There have also been reports of acute leukopenia and hepatotoxicity. Salivation and inertia (Ghanizadez 2014).  Increased FT3 (free tri-iodothyronine) levels (Margari 2013).

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 risperidone solution is incompatible with tea; the drink contains benzoic acid that forms a precipitate with tannins from tannin-containing tea (green tea and black tea).

Summary
Risperidone has no effect on the core symptoms of autism spectrum disorders. A treatment programme including psychosocial and educational intervention should be drawn up. Inform patients about the increase in bodyweight. Fasting glucose and lipid levels should be determined. Follow up if the use is prolonged because of the potential for effects on the capacity to learn. Be aware of the occurrence of tardive dyskinesia. Do not increase the dosage in cases of akathisia. Regular clinical checks of the endocrine status are recommended.

None of the currently available psychopharmaceuticals have any primary effect on the core symptoms of autism spectrum disorders. However, medication can reduce the behavioural problems that are often associated with autism.

Pharmacological treatment should be an integral part of a more comprehensive treatment programme, including psychosocial and educational intervention.

When prescribing risperidone, the patient and parents should be warned about the increase in appetite. The baseline weight needs to be determined and monitored. It is recommended that recommendation on diet and exercise should be given.

The fasting glucose and lipid levels should be determined before and during treatment with risperidone (e.g. after 1 month, 3 months and then every six months or every year).

Sedation with risperidone should be closely monitored in children because there are potential consequences for their learning ability. Changing the moment of administration may possibly improve the impact of sedation on concentration for children and adolescents.

During treatment with risperidone, regular checks should be made for extrapyramidal symptoms and other motor disorders. Extrapyramidal symptoms occurring indicates a risk factor for tardive dyskinesia. Consider discontinuing all antipsychotic drugs if signs and symptoms of tardive dyskinesia appear.

Because of the potential effects of prolonged hyperprolactinaemia on growth and sexual maturation in children and adolescents, regular clinical monitoring of the endocrine status should be considered, including measurements of height, weight, sexual maturation, monitoring of menstrual function and other possible effects of prolactin.

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

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
	Haloperidol Related Medicines Menu">	N05AD01
	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

References

1. Chavez B, et al, Role of risperidone in children with autism spectrum disorder., Ann Pharmacother., 2006, 40, 909-16
2. Anderson GM, et al, Effects of short- and long-term risperidone treatment on prolactin levels in children with autism, Biol Psychiatry, 2007, 6, 545-50
3. Aman MG, et al, Plasma pharmacokinetic characteristics of risperidone and their relationship to saliva concentrations in children with psychiatric or neurodevelopmental disorders, Clin Ther, 2007, 29, 1476-86
4. Fraguas D, et al, Metabolic and hormonal side effects in children and adolescents treated with second-generation antipsychotics, J Clin Psychiatry, 2008, 69, 1166-75
5. Findling RL, Atypical antipsychotic treatment of disruptive behavior disorders in children and adolescents, J Clin Psychiatry, 2008, 69 Suppl 4, 9-14
6. Gencer O, et al, Comparison of long-term efficacy and safety of risperidone and haloperidol in children and adolescents with autistic disorder. An open label maintenance study, Eur Child Adolesc Psychiatry., 2008, 17, 217-25
7. Haas M, et al, Treating disruptive behavior disorders with risperidone: a 1-year, open-label safety study in children and adolescents, J Child Adolesc Psychopharmacol, 2008, 18, 337-45
8. Luby J, et al, Risperidone in preschool children with autistic spectrum disorders: an investigation of safety and efficacy., J Child Adolesc Psychopharmacol., 2006, 16, 575-87
9. MacMillan CM, et al, Comparative clinical responses to risperidone and divalproex in patients with pediatric bipolar disorder, J Psychiatr Pract., 2008, 14, 160-9
10. Pandina GJ, et al, Risperidone in the management of disruptive behavior disorders, J Child Adolesc Psychopharmacol., 2006, 16, 379-92
11. Reyes M, et al, Long-term use of risperidone in children with disruptive behavior disorders and subaverage intelligence: efficacy, safety, and tolerability, J Child Adolesc Psychopharmacol, 2006, 16, 260-72
12. Sikich L, Efficacy of atypical antipsychotics in early-onset schizophrenia and other psychotic disorders, J Clin Psychiatry, 2008, 69, 21-5
13. Troost PW, et al, Long-term effects of risperidone in children with autism spectrum disorders: a placebo discontinuation study, J Am Acad Child Adolesc Psychiatry, 2005, 44, 1137-44
14. NVK, Richtlijn Pediatrisch Delier, www.nvk.nl, 2013
15. Turkel SB et al. , The diagnosis and management of delirium in infancy. , J Child Adolesc Psychopharmacol. , 2013 , 23, 352-6.
16. Turkel SB et al., Atypical antipsychotic medications to control symptoms of delirium in children and adolescents., J Child Adolesc Psychopharmacol., 2012, 22, 126-30
17. Kent JM et al., Risperidone dosing in children and adolescents with autistic disorder: a double-blind, placebo-controlled study., J Autism Dev Disord., 2013, 43, 1773-83
18. Aman MG et al. , Medication and parent training in children with pervasive developmental disorders and serious behavior problems: results from a randomized clinical trial. , J Am Acad Child Adolesc Psychiatry. , 2009, 48, 1143-54.
19. Ghanizadeh A et al. , A head-to-head comparison of aripiprazole and risperidone for safety and treating autistic disorders, a randomized double blind clinical trial. , Child Psychiatry Hum Dev. , 2014, 45, 185-92
20. Swadi HS et al., A trial of quetiapine compared with risperidone in the treatment of first onset psychosis among 15- to 18-year-old adolescents., Int Clin Psychopharmacol., 2010, 25, 1-6
21. Pandina G et al., An open-label, multicenter evaluation of the long-term safety and efficacy of risperidone in adolescents with schizophrenia., hild Adolesc Psychiatry Ment Health., 2012, 6, 23
22. Geller B et al. , A randomized controlled trial of risperidone, lithium, or divalproex sodium for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents. , Arch Gen Psychiatry. , 2012, 69, 515-28
23. Pavuluri MN et al. , Double-blind randomized trial of risperidone versus divalproex in pediatric bipolar disorder. , Bipolar Disord. , 2010, 12, 593-605
24. Ghanizadeh A et al. , Aripiprazole versus risperidone for treating children and adolescents with tic disorder: a randomized double blind clinical trial. , Child Psychiatry Hum Dev. , 2014, 45, 596-603
25. Roessner V et al., European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment., Eur Child Adolesc Psychiatry., 2011, 20, 173-96
26. Pringsheim T et al., Canadian guidelines for the evidence-based treatment of tic disorders: pharmacotherapy., Can J Psychiatry., 2012, 57, 133-43
27. Riahi F et al., Comparison between the efficacies of Risperidone with Haloperidol in the treatment of attention-deficit hyperactivity disorder (ADHD) among preschoolers: a randomized double-blind clinical trial., Electron Physician., 2016, 8, 2840-8
28. Safavi P et al. ., Comparison of risperidone and aripiprazole in the treatment of preschool children with disruptive behavior disorder and attention deficit-hyperactivity disorder: A randomized clinical trial. , J Adv Pharm Technol Res. , 2016, 7, 43-7
29. Janssen-Cilag B.V. ., SmPC Risperdal drank (RVG 19127) 22-2-2017, www.geneesmiddeleninformatiebank.nl
30. Margari L et al. , Tolerability and safety profile of risperidone in a sample of children and adolescents. , Int Clin Psychopharmacol. , 2013 , Jul;28(4), 177-83
31. Malas N et al. , Pediatric Delirium: Evaluation, Management, and Special Considerations. , Curr Psychiatry Rep. , 2017 , Aug 12;19(9):, 65
32. Ganos C et al., Tics in the Pediatric Population: Pragmatic Management., Mov Disord Clin Pract., 2017, 4, 160-72
33. Margari L et al., Tolerability and safety profile of risperidone in a sample of children and adolescents., Int Clin Psychopharmacol., 2013, Jul;28(4), 177-83
34. Aman MG et al., Medication and parent training in children with pervasive developmental disorders and serious behavior problems: results from a randomized clinical trial., J Am Acad Child Adolesc Psychiatry., 2009, 48, 1143-54.
35. Geller B et al., A randomized controlled trial of risperidone, lithium, or divalproex sodium for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents., Arch Gen Psychiatry., 2012, 69, 515-28
36. Turkel SB et al., The diagnosis and management of delirium in infancy., J Child Adolesc Psychopharmacol., 2013, 23, 352-6.
37. Malas N et al., Pediatric Delirium: Evaluation, Management, and Special Considerations., Curr Psychiatry Rep., 2017, Aug 12;19(9):, 65
38. Ghanizadeh A et al., A head-to-head comparison of aripiprazole and risperidone for safety and treating autistic disorders, a randomized double blind clinical trial., Child Psychiatry Hum Dev., 2014, 45, 185-92
39. Ghanizadeh A et al., Aripiprazole versus risperidone for treating children and adolescents with tic disorder: a randomized double blind clinical trial., Child Psychiatry Hum Dev., 2014, 45, 596-603
40. Safavi P et al. ., Comparison of risperidone and aripiprazole in the treatment of preschool children with disruptive behavior disorder and attention deficit-hyperactivity disorder: A randomized clinical trial., J Adv Pharm Technol Res., 2016, 7, 43-7
41. Pavuluri MN et al., Double-blind randomized trial of risperidone versus divalproex in pediatric bipolar disorder., Bipolar Disord., 2010, 12, 593-605

Changes