Pharmacokinetics in children

The following kinetic parameters have been observed with single and multiple doses of 50-200 mg/day (Alderman J et al. 1998, Axelson DA et al. 2002):

In a study by Taurines R et al. in 2013, a moderate correlation between the daily dose of sertraline and the Css was found. No link was seen between the serum concentrations and the clinical outcome (effect).

Sertraline is almost entirely metabolized. The key metabolite is the weakly effective desmethylsertraline, which is formed by CYP2C19. Sertraline is metabolized further by CYP3A4 and CYP2B6.

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

Very common: headaches, insomnia, diarrhoea, nausea.

Common: chest pain, mania, pyrexia, vomiting, anorexia, affective lability, aggression, nervousness, attention disorder, dizziness, hyperkinesia, migraine, drowsiness, tremors, visual disorder, dry mouth, dyspepsia, nightmares, fatigue, urinary incontinence, rash, acne, epistaxis, flatulence.

Uncommon: extended QT in the ECG, suicide attempt, convulsion, extrapyramidal disorder, paraesthesias, depression, hallucination, purpura, hyperventilation, anaemia, abnormal functioning of the liver, increased alanine aminotransferase, cystitis, herpes simplex, outer ear inflammation, earache, eye pain, mydriasis, malaise, haematuria, pustular rash, rhinitis, lesions, weight loss, muscle contraction, abnormal dreams, apathy, albuminuria, pollakiuria, polyuria, pain in the breasts, menstrual disorder, alopecia, dermatitis, skin abnormalities, abnormal skin odour, urticaria, bruxism, flushing.

Unknown: enuresis [SmPC for Asentra and Enore]

Also reported: sedation, movement disorders (including extrapyramidal symptoms such as tooth grinding, hypertonia, hyperkinesia and unsteady gait), vision disorders (such as accommodation disorders) [Taurines 2013], polydipsia [Taurines 2013], suicidal thoughts and suicidal behaviour. A number of cases of serotonin syndrome have also been described in the literature.

In cases of long-term treatment, some cases have been reported post-marketing of delayed growth and delayed puberty. The clinical relevance and the causal relationship are unclear [SmPC for Asentra and Enore].

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
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. The sertraline concentrate for oral use contains 12% alcohol and is therefore unsuitable for children. When sertraline is being used, be aware also of the possibility of serotonin syndrome occurring.

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

Severe psychiatric side effects such as hostility, aggression, self-harming behaviour, suicidal thoughts and suicide attempts occur in children and adolescents with depressive symptoms. Screening for suicide risks is indicated before the treatment. 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 sertraline 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.

The sertraline concentrate for solutions for oral use contains 12% alcohol and should not be used in children.

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.

If severe side effects occur of if there is no effect, it is possible that the metabolization of the drug may be different. CYP2C19 can determine the variation in response. Genotyping can be considered.

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. Garland EJ, Facing the evidence: antidepressant treatment in children and adolescents, CMAJ, 2004, 17:170, 489-91
2. Cook EH, et al, Long-term sertraline treatment of children and adolescents with obsessive-compulsive disorder, J Am Acad Child Adolesc Psychiatry, 2001, 40, 1175-81
3. Axelson DA, et al, Sertraline pharmacokinetics and dynamics in adolescents., J Am Acad Child Adolesc Psychiatry, 2002, 41, 1037-44
4. Asbahr FR, et al, Group cognitive-behavioral therapy versus sertraline for the treatment of children and adolescents with obsessive-compulsive disorder, J Am Acad Child Adolesc Psychiatry, 2005, 44, 1128-36
5. Alderman J, et al, Sertraline treatment of children and adolescents with obsessive-compulsive disorder or depression: pharmacokinetics, tolerability, and efficacy, J Am Acad Child Adolesc Psychiatry, 1998, 37, 386-94
6. March JS, et al, Sertraline in children and adolescents with obsessive-compulsive disorder: a multicenter randomized controlled trial, JAMA, 1998, 280:, 1752-6
7. March JS, et al, Treatment benefit and the risk of suicidality in multicenter, randomized, controlled trials of sertraline in children and adolescents, J Child Adolesc Psychopharmacol, 2006, 19, 91-102
8. Pediatric OCD Treatment Study (POTS) Team, Cognitive-behavior therapy, sertraline, and their combination for children and adolescents with obsessive-compulsive disorder: the Pediatric OCD Treatment Study (POTS) randomized controlled trial., JAMA, 2004, 292, 1969-76
9. Wagner KD, et al, Remission status after long-term sertraline treatment of pediatric obsessive-compulsive disorder., J Child Adolesc Psychopharmacol, 2003, 13, S53-60
10. Wilens TE, et al, Absence of cardiovascular adverse effects of sertraline in children and adolescents, J Am Acad Child Adolesc Psychiatry., 1999, 38, 573-7
11. KRKA, d.d., Novo mesto, SmPC Asentra (RVG 28404) 23-11-2017, www.geneesmiddeleninformatiebank.nl
12. Pfizer bv, SmPC Enore (RVG 110362) 21-02-2018, www.geneesmiddeleninformatiebank.nl
13. Skarphedinsson G et al, J Child Adolesc, Sertraline treatment of nonresponders to extended cognitive-behavior therapy in pediatric obsessive-compulsive disorder., J Child Adolesc Psychopharmacol, 2015, 27(7), 574-9
14. NICE, Clinical Guideline Obsessive-compulsive disorder and body dismorphic disorder, 2005
15. Walkup JT et al,, Cognitive Behavioral Therapy, Sertraline, or a Combination in Childhood Anxiety., N Engl J Med., 2008, Dec 25;359(26), 2753-66
16. Iftene F et al. , Rational-emotive and cognitive-behavior therapy (REBT/CBT) versus pharmacotherapy versus REBT/CBT plus pharmacotherapy in the treatment of major depressive disorder in youth: a randomized clinical trial., Psychiatry Res., 2015, Feb 28;225(3), 687-94
17. NICE, Clinical guideline Depression in children and young people: identifification and management,, 2005
18. Taurines R et al., The relation between dosage, serum concentrations, and clinical outcome in children and adolescents treated with sertraline: a naturalistic study., Ther Drug Monit., 2013, Feb;35(1), 84-91
19. Accord Healthcare, SmPC Sertralin Accord 50 mg | 100 mg Filmtabletten (99727.00.00/99728.00.00), 05/2018
20. NICE, Clinical guideline Depression in children and young people: identifification and management,, 2005
21. Iftene F et al., Rational-emotive and cognitive-behavior therapy (REBT/CBT) versus pharmacotherapy versus REBT/CBT plus pharmacotherapy in the treatment of major depressive disorder in youth: a randomized clinical trial., Psychiatry Res., 2015, Feb 28;225(3), 687-94

Changes

Therapeutic Drug Monitoring

Overdose