Pharmacokinetics in children

The following pharmacokinetic parameters were calculated in a population kinetics model, based on data from 428 children aged 7-18 years:

Clearance and volume of distribution are greater in children aged 7-18 years than in adults. The half-life is therefore shorter and the steady-state plasma concentration lower than in adults. These pharmacokinetic differences do not affect efficacy. Children from 7 years old can receive the same dose as adults (Lobo et al. 2014, Prakash et al. 2012).

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: 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

Common (≥ 5%): Nausea, diarrhea, weight loss, dizziness.

Furthermore, abdominal pain, vomiting, dry mouth, fatigue, decreased appetite, headache, insomnia, drowsiness, oropharyngeal pain, cough.

The type of side effects in children generally correspond to the type of side effects in adults (Lilly USA 2019).

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:
Leads to reduced ability to react and concentrate. Do not use in depression. Carefully observe patients, especially high risk patients (with suicidal ideation, suicide attempt) for the increased risk of suicide. Suicidal thoughts and behaviors can also arise during early antidepressant treatment for conditions other than depression. Regular testing for mania / hypomania is recommended. Also, when using duloxetine, one should be aware of the development of serotonin syndrome. Furthermore, monitoring of growth and development is necessary in children and adolescents.

Use can lead to reduced ability to react and concentrate. Many daily activities can be hindered by this.

Prior to treatment, screening for risk of suicide and bipolar disorder is indicated. Suicidal thoughts and behaviors can also arise during early antidepressant treatment for conditions other than depression. Therefore, the same precautions as in the treatment of patients with depression should be followed when treating patients with generalized anxiety disorders. Patients, especially high-risk patients (suicidal thoughts, suicide attempt), should be carefully monitored during treatment with these drugs, especially at the start of treatment and after dose adjustments. Patients should be alerted about the need to monitor for any clinical worsening, suicidal behavior or thoughts and unusual changes in behavior and to seek medical advice immediately if these symptoms present.

Serotonin syndrome has been rarely reported; a combination of symptoms such as agitation, tremors, myoclonus and hyperthermia should be suspected.

Weight and height should be regularly monitored while taking duloxetine.

When duloxetine is stopped, the following symptoms may occur: headache, dizziness, insomnia, and abdominal pain. To prevent withdrawal symptoms, duloxetine should be tapered; weekly at 30 mg / day or slower (Horikx et al. 2019).

The effectiveness of duloxetine in depression in children aged 7 to 17 years has not been demonstrated (Atkinson et al. 2014, Emslie et al. 2014).

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. Lilly USA, LLC., Full prescribing information Cymbalta (ref. ID 4502314, www.accessdata.fda.gov, 2019
2. Prakash, A., et al, An open-label safety and pharmacokinetics study of duloxetine in pediatric patients with major depression., J Child Adolesc Psychopharmacol, 2012, 22(1), 48-55
3. Emslie, G. J., et al, A double-blind efficacy and safety study of duloxetine fixed doses in children and adolescents with major depressive disorder., J Child Adolesc Psychopharmacol, 2014, 24(4), 170-9
4. Lobo, E. D., et al, Pharmacokinetics of orally administered duloxetine in children and adolescents with major depressive disorder, Clin Pharmacokinet, 2014, C53(8), 731-40
5. Atkinson, S. D., et al, A double-blind efficacy and safety study of duloxetine flexible dosing in children and adolescents with major depressive disorder., J Child Adolesc Psychopharmacol, 2014, 24(4), 180-9
6. Horikx, A., et al., Multidisciplinair document ‘Afbouwen SSRI’s & SNRI’s’., www.nhg.org, 2019
7. Strawn, J. R.,et al, A randomized, placebo-controlled study of duloxetine for the treatment of children and adolescents with generalized anxiety disorder., J Am Acad Child Adolesc Psychiatry, 2015, 54(4), 283-93

Changes

Therapeutic Drug Monitoring

Overdose