Pharmacokinetics in children

Metabolization: extensively in the liver, mainly by CYP3A4, to the active compound N-desalkylquetiapine and other metabolites.

The following kinetic parameters have been observed [Findling ’06, McConville ’00 and Winter ’08]:

Study	Findling (n=17)	Winter (n=9)	Winter (n=12) + McConville (n=10)	Winter (n=29)
Age	6-12 yrs	10-12 yrs	13-17 yrs	Adults
Dose	avg. 4.4 mg/kg/day	800 mg/day	800 mg/day	800 mg/day
Cmax (ng/ml)	-	1426.3 ± 33.9	924.7–991.9	1124.6 ± 31.9
Tmax (h)	1.0 ± 0.5 (0.5–2)	1.50 (1–2)	0.55–3	1.23 (0.5–3)
t½ (h)	2.9 ± 0.9 (1.8–4.3)	5.52 ± 1.38	5.3–5.52	5.10 ± 0.91
Cl (l/h/kg)	3.0 ± 1.3 (1.4–4.9)	-	-	-
Vd (l/kg)	11.8 ± 3.7 (4.9–17.3)	-	-	-

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

Short-term treatment of sleep problems resulting from acute psychiatric disturbance

Oral Normal preparation (immediate release) 12 years up to 18 years Before the night: 12.5 - 50 mg/day in 1 dose There is no evidence about the use of quetiapine as a hypnotic. If a decision is made to treat with quetiapine nonetheless, the following factors should be taken into account: The long-term consequences (effect on weight, glucose and lipids) of low doses of quetiapine are unclear. Once the treatment has proved to be effective, it is very difficult to stop it again. Quetiapine should be prescribed by a specialist in child and youth psychiatry. The dosage should be determined individually and the lowest possible dose should be used.

Bipolar disorder, type 1

Oral Normal preparation (immediate release) 12 years up to 18 years [3] [4] [5] [10] [18] [20] [21] [22] Week 1: 100 mg/day in 2 doses Week 2: 200 mg/day in 2 doses Week 3: 300 mg/day in 2 doses Week 4: 400 mg/day in 2 doses 400 mg/day is usually sufficient. Increase further if necessary, depending on the clinical response and the tolerance. Doses of up to 600 mg/day have been used in the literature. A faster build-up regimen can be used if necessary, increasing the dosage every day or every few days. Because of the risk of acute withdrawal symptoms, the treatment should be phased out gradually. Quetiapine should be prescribed by a specialist in child and youth psychiatry. The dosage should be determined individually and the lowest possible dose should be used.

Insomnia

Oral Normal preparation (immediate release) 12 years up to 18 years [25] Before the night: 12.5 - 50 mg/day in 1 dose There is no evidence about the use of quetiapine as a hypnotic. If a decision is made to treat with quetiapine nonetheless, the following factors should be taken into account: The long-term consequences (effect on weight, glucose and lipids) of low doses of quetiapine are unclear. Once the treatment has proved to be effective, it is very difficult to stop it again. Quetiapine should be prescribed by a specialist in child and youth psychiatry. The dosage should be determined individually and the lowest possible dose should be used.

Renal impaiment in children > 3 months

GFR ≥10 ml/min/1.73m2: Dose adjustment not required.

GFR <10 ml/min/1.73m2: A general recommendation on dose adjustment cannot be provided.

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

Sedation, rhinitis, agitation, fatigue, sleeplessness.

In children of 10–17 years, elevated blood pressure is also very common. Increased appetite, hyperprolactinaemia and extrapyramidal symptoms are also more common than in adults.

 

 

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

As with other antipsychotics, when using quetiapine 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.

Children and adolescents are more likely than adults to experience suicide-related events.

Quetiapine should be prescribed by a specialist in child and youth psychiatry. The dosage should be determined individually and the lowest possible dose should be used.

 

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

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. Castro-Fornieles J, et al, Antipsychotic treatment in child and adolescent first-episode psychosis: a longitudinal naturalistic approach, J Child Adolesc Psychopharmacol., 2008, 18, 327-36
2. Connor DF, et al, Randomized controlled pilot study of quetiapine in the treatment of adolescent conduct disorder., J Child Adolesc Psychopharmacol, 2008, 18, 140-56
3. DelBello MP, et al, A 12-week single-blind trial of quetiapine for the treatment of mood symptoms in adolescents at high risk for developing bipolar I disorder., J Clin Psychiatry., 2007, 68, 789-95
4. DelBello MP, et al, A double-blind randomized pilot study comparing quetiapine and divalproex for adolescent mania, J Am Acad Child Adolesc Psychiatry, 2006, 45, 305-13
5. Delbello MP, et al, A double-blind, randomized, placebo-controlled study of quetiapine as adjunctive treatment for adolescent mania, Am Acad Child Adolesc Psychiatry, 2002, 41, 1216-23
6. Findling RL, Use of quetiapine in children and adolescents, J Clin Psychiatry, 2002, 63 Suppl 13, 27-31
7. Findling RL, et al, A 26-week open-label study of quetiapine in children with conduct disorder., J Child Adolesc Psychopharmacol, 2007, Feb 17(1), 1-9
8. Findling RL, et al, Effectiveness, safety, and pharmacokinetics of quetiapine in aggressive children with conduct disorder., J Am Acad Child Adolesc Psychiatry.;:., 2006, 45, 792-800
9. Kronenberger WG, et al, Quetiapine addition in methylphenidate treatment-resistant adolescents with comorbid ADHD, conduct/oppositional-defiant disorder, and aggression: a prospective, open-label study, J Child Adolesc Psychopharmacol.;:., 2007, 17, 334-47
10. Marchand WR, et al, Quetiapine adjunctive and monotherapy for pediatric bipolar disorder: a retrospective chart review, J Child Adolesc Psychopharmacol.;, 2004, 14, 405-11
11. McConville BJ, et al, Pharmacokinetics, tolerability, and clinical effectiveness of quetiapine fumarate: an open-label trial in adolescents with psychotic disorders, J Clin Psychiatry., 2000, 61, 252-60
12. McConville B, et al, Long-term safety, tolerability, and clinical efficacy of quetiapine in adolescents: an open-label extension trial., J Child Adolesc Psychopharmacol, 2003, 13, 73–80
13. Schimmelmann BG, et al, A prospective 12-week study of quetiapine in adolescents with schizophrenia spectrum disorders, J Child Adolesc Psychopharmacol, 2007, 17, 768-78
14. Shaw JA, et al, A study of quetiapine: efficacy and tolerability in psychotic adolescents, J Child Adolesc Psychopharmacol, 2001, 11, 415–424
15. Stevens JR, et al, Elevated prolactin levels in male youths treated with risperidone and quetiapine, J Child Adolesc Psychopharmacol, 2005, 15, 893-900
16. Winter HR, et al, Steady-state pharmacokinetic, safety, and tolerability profiles of quetiapine, norquetiapine, and other quetiapine metabolites in pediatric and adult patients with psychotic disorders, J Child Adolesc Psychopharmacol, 2008, 18, 81-98
17. Arango C, et al,, Olanzapine compared to quetiapine in adolescents with a first psychotic episode., Eur Child Adolesc Psychiatry., 2009, Jul;18(7), 418-28
18. DelBello MP, et al, A double-blind, placebo-controlled pilot study of quetiapine for depressed adolescents with bipolar disorder., Bipolar Disord., 2009, Aug;11(5), 483-93
19. Findling RL et al, Efficacy and safety of quetiapine in adolescents with schizophrenia investigated in a 6-week, double-blind, placebo-controlled trial, J Child Adolesc Psychopharmacol, 2012, Oct;22(5), 327-42
20. Findling RL et al, Efficacy and safety of extended-release quetiapine fumarate in youth with bipolar depression: an 8 week, double-blind, placebo-controlled trial., J Child Adolesc Psychopharmacol, 2014, Aug;24(6), 325-35
21. Masi G et al, Efficacy and Safety of Risperidone and Quetiapine in Adolescents With Bipolar II Disorder Comorbid With Conduct Disorder, J Clin Psychopharmacol, 2015, Oct;35(5), 587-90
22. Pathak S, et al,, Efficacy and safety of quetiapine in children and adolescents with mania associated with bipolar I disorder: a 3-week, double-blind, placebo-controlled trial., J Clin Psychiatry., 2013, Jan;74(1), e100-9
23. 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, Jan;25(1), 1-6
24. Loy JH et al, Atypical antipsychotics for disruptive behaviour disorders in children and youths., Cochrane Database Syst Rev, 2017, Aug 9;8, CD008559
25. Kenniscentrum Kinder- en Jeugdpsychiatrie., Expert opinie. 17-4-2018
26. Online GL. Gelbe Liste Online, https://www.gelbe-liste.de/, Accessed June 12, 2018
27. Astra, SmPC Seroquel Prolong 50mg/150mg/200mg/300mg/400mg Retardtabletten (70561.00.00), 01/2018
28. neuraxpharm, SmPC Quetiapin 25mg/50mg/100mg/150mg/200mg/300mg (76806.00.00), 02/2017
29. Astra, SmPC Seroquel 25mg/100mg/200mg/300mg Filmtabletten (47291.00.00), 01/2018
30. AL, SmPC Quetiapin 50mg/150mg/200mg/300mg/400mg Retardtabletten (92819.00.00), 11/2016
31. AbZ, SmPC Quetiapin 50mg/150mg/200mg/300mg/400mg Retardtabletten (83076.00.00), 09/2017
32. Hexal, SmPC Quetiapin 25mg/50mg/100mg/150mg/200mg/300mg/400mg Filmtabletten (71238.00.00), 05/2016
33. Astra, SmPC Seroquel Prolong 50mg/150mg/200mg/300mg/400mg Retardtabletten (70561.00.00), 01/2018

Changes