Pharmacokinetics in children

The average fluoxetine concentration in children aged 8 years and upwards is approximately twice that observed in adolescents and the average norfluoxetine concentration is 1.5 times higher. Steady-state plasma concentrations depend on the bodyweight and are higher in children whose weight is lower. As in adults, fluoxetine and norfluoxetine accumulate significantly after multiple oral doses; steady-state concentrations were achieved within 3-4 weeks of daily dosing.

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

Renal impaiment in children > 3 months

GFR ≥10 ml/min/1.73m2: no dose adjustment needed
GFR <10 ml/min/1.73m2: general advice cannot be given. Consider dosing the starting dose every other day, then increasing it based on clinical response and tolerability.

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

In children and adolescents: more chance of suicidal behaviour, hostility, mania or hypomania, epistaxis; reports of growth retardation, decreased alkaline phosphatase levels and side effects that may indicate delayed sexual development or sexual dysfunction.

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

Summary:
When treating depression and social phobia, combine the medicinal therapy with psychotherapy at the same time. Results in a reduced capacity to react and concentrate; monitor patients closely and high-risk patients in particular (suicidal thoughts, suicide attempts) due to the increased risk of suicide; discontinue the treatment if there are manic reactions. Regular examination for mania/hypomania is recommended. When fluoxetine is being used, be aware also of the possibility of serotonin syndrome occurring. Furthermore, checking the growth and development is necessary in children and adolescents.

Fluoxetine should only be given to a child or adolescent with moderate to severe depression in combination with simultaneous psychotherapy (cognitive behavioural therapy). Cognitive behavioural therapy is also an effective therapeutic option for treating social phobias. Depending on the severity of the condition, this therapy can be combined with medicinal therapy.

Using it can result in reduced capacity to react and concentrate. This can hinder numerous day-to-day activities.

Screening for suicide risks and bipolar disorder is indicated before the treatment. Antidepressant treatment can increase the risk of suicidality (made greater by the depression) yet further during the early stages of recovery. Patients – particularly those at high risk because of suicidal thoughts or suicide attempts – must be monitored closely during treatment with these drugs, in particular when treatment is commenced and after dosage changes. Patients must be made aware of the need to keep an eye on any clinical exacerbation, suicidal behaviour or suicidal thoughts and unusual behavioural changes and of the need to obtain medical advice immediately if these symptoms occur. Patients must not be allowed to have large amounts of this drug available.

Other psychiatric conditions for which fluoxetine is prescribed can also be associated with an increased risk of suicide-related events. Moreover, there may be comorbidity of these conditions with episodes of more severe depression. The same precautionary measures that need to be considered when treating patients with severe depression disorders must therefore be considered when treating patients with other psychiatric conditions.

In paediatric clinical trials, manic reactions (including mania and hypomania) were often reported. Regular examination for mania/hypomania is recommended. Treatment with fluoxetine should be discontinued if there are manic reactions.

There have been rare reports of serotonin syndrome with SSRIs; this should be borne in mind if there is a combination of symptoms such as agitation, tremors, myoclonic episodes and hyperthermia. If there are seizures, the medication should be discontinued.

Furthermore, the growth and development in children and adolescents need to be checked because there is insufficient data on the effects of fluoxetine on growth and on sexual, cognitive and emotional development.

Because of the interaction with dextromethorphan, be aware of the use of self-care products with dextromethorphan (cough syrups and capsules).

Interactions

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

• NERVOUS SYSTEM
• PSYCHOANALEPTICS

ANTIDEPRESSANTS

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

References

1. Emslie G, et al, Treatment for Adolescents with Depression Study (TADS): safety results, J Am Acad Child Adolesc Psychiatry, 2006, 45, 1440-55
2. Emslie GJ, et al, Fluoxetine versus placebo in preventing relapse of major depression in children and adolescents, Am J Psychiatry, 2008, 165, 459-67
3. Emslie GJ, et al., Fluoxetine for acute treatment of depression in children and adolescents: a placebo-controlled, randomized clinical trial., J Am Acad Child Adolesc Psychiatry., 2002, 41, 1205-15
4. Clark DB, et al, Fluoxetine for the treatment of childhood anxiety disorders: open-label, long-term extension to a controlled trial, J Am Acad Child Adolesc Psychiatry, 2005, 44, 1263-70
5. Beidel DC, et al, SET-C versus fluoxetine in the treatment of childhood social phobia., J Am Acad Child Adolesc Psychiatry, 2007, 46, 1622-32
6. Birmaher B, et al, Fluoxetine for the treatment of childhood anxiety disorders, J Am Acad Child Adolesc Psychiatry, 2003, 42, 415-23
7. Emslie GJ, et al, A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression, Arch Gen Psychiatry, 1997, 54, 1031-7
8. Geller DA, et al, Fluoxetine Pediatric OCD Study Team. Fluoxetine treatment for obsessive-compulsive disorder in children and adolescents: a placebo-controlled clinical trial, J Am Acad Child Adolesc Psychiatry, 2001, 40, 773-9
9. Heiligenstein JH, et al, Fluoxetine 40-60 mg versus fluoxetine 20 mg in the treatment of children and adolescents with a less-than-complete response to nine-week treatment with fluoxetine 10-20 mg: a pilot study, J Child Adolesc Psychopharmacol., 2006, 16, 207-17
10. Liebowitz MR, et al, Fluoxetine in children and adolescents with OCD: a placebo-controlled trial, J Am Acad Child Adolesc Psychiatry, 2002, 41, 1431-8
11. March J, et al, Treatment for Adolescents with Depression Study (TADS) team. Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents with depression Study (TADS) randomized controlled trial, JAMA, 2004, 292, 807-20
12. Riddle MA, et al, Double-blind, crossover trial of fluoxetine and placebo in children and adolescents with obsessive-compulsive disorder., J Am Acad Child Adolesc Psychiatry, 1992, 31, 1062-9
13. Rohde P, et al, Achievement and maintenance of sustained response during the Treatment for Adolescents With Depression Study continuation and maintenance therapy, Arch Gen Psychiatry, 2008, 65, 447
14. Wilens TE, et al, Fluoxetine pharmacokinetics in pediatric patients, J Clin Psychopharmacol, 2002, 22, 568-75
15. Kennard BD, et al., Remission and recovery in the treatment for adolescents with depression study (TADS): acute and long-term outcomes, , J Am Acad Child Adolesc Psychiatry, 2009, 48, 186-95
16. Treatment for adolescents with depression study (TADS) Team, et al., The treatment for adolescents with depression study (TADS): outcomes over 1 year of naturalistic follow-up., Am J Psychiatry., 2009, 166, 1141-9
17. Da Costa CZ, et al., Comparison among clomipramine, fluoxetine, and placebo for the treatment of anxiety disorders in children and adolescents., J Child Adolesc Psychopharmacol., 2013, 23, 687-92
18. Kotler LA, et al, An open trial of fluoxetine for adolescents with bulimia nervosa., J Child Adolesc Psychopharmacol., 2003, 13, 329-35
19. Kenniscentrum Kinder- en Jeugdpsychiatrie., Expertopinie dosering boulimia nervosa en body dysmorphic disorder, 13-07-2018
20. Heimann SW, SSRI for body dysmorphic disorder, J Am Acad Child Adolesc Psychiatry, 1997, 36, 868
21. Albertini RS., Body dysmorphic disorder, J Am Acad Child Adolesc Psychiatry, 1996, 35, 1425-6
22. Phillips KA., Case study: body dysmorphic disorder in adolescents., J Am Acad Adolesc Psychiatry, 1995, 34, 1216-20
23. Hexal, SmPC Fluoxetin HEXAL 10 mg Tabletten (40254.00.00), 09/2017
24. Nagler, E.V. et al, Antidepressants for depression in stage 3–5 chronic kidney disease: a systematic review of pharmacokinetics, efficacy and safety with recommendations by European Renal Best Practice (ERBP), , Nephrology Dialysis Transplantation, 2012, 27 (10), 3736–3745
25. Kennard BD, et al., Remission and recovery in the treatment for adolescents with depression study (TADS): acute and long-term outcomes,, J Am Acad Child Adolesc Psychiatry, 2009, 48, 186-95
26. Nagler, E.V. et al, Antidepressants for depression in stage 3–5 chronic kidney disease: a systematic review of pharmacokinetics, efficacy and safety with recommendations by European Renal Best Practice (ERBP),, Nephrology Dialysis Transplantation, 2012, 27 (10), 3736–3745

Changes

Therapeutic Drug Monitoring

Overdose