Pharmacokinetics in children

Metabolization: inter alia hydroxylation via CYP2D6 to the active metabolite 10-hydroxynortriptyline. Elimination: mainly with the urine. The following kinetic parameters have been observed:

Children aged 5-12 years have a significantly shorted t½ and a significantly longer apparent oral Cl than adolescents. The individual variation in t½ is large (four to sixfold) [Geller B et al. 1987].

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

No information available on dose adjustment in renal impairment.

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

Tricyclic antidepressants (TCAs) cause ECG changes in children (PR, QT and QRS extension). Despite the fact that no causal link between the sudden deaths of four children between 1990 and 1997 and treatment with desipramine could be established, a great deal of caution is recommended with TCAs. Furthermore, TCAs often cause anticholinergic, alpha-adrenolytic and antihistaminergic side effects: tachycardia, dry mouth (sometimes resulting in more caries), sedation, tremor, constipation, dizziness, blurred vision, sleep disorders, weight gain, headaches, abdominal pain and sexual function disorders. Due to the demonstrable effect of these drugs on the ECG and the resulting risk of arrhythmia, prescribing a TCA is only defensible as a last resort.

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; do not give in cases of depression; monitor patients closely and high-risk patients in particular (suicidal thoughts, suicide attempts) due to the increased risk of suicide. Measure the blood pressure, pulse rate and ECG before and during the treatment; be aware also of cardiac complaints arising or being exacerbated. Symptoms such as dizziness and heart palpitations must be addressed immediately. Dental checks are indicated because of the greater risk of caries.

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

Contrary to the situation in adults, using TCAs is not recommended in children and adolescents with depression; the efficacy and safety have not been demonstrated and cases with fatal outcomes are known.

Screening for suicide risks is indicated before the treatment. Antidepressant treatment can increase the risk of suicide (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.

When TCAs are being used, attention must be paid to any cardiac problems in the patient and their family, as this group of drugs can worsen existing or hereditary vulnerability to arrhythmia. The blood pressure, pulse and ECG also need to be checked before and during treatment. In addition, because of these cardiac side effects, symptoms such as dizziness and heart palpitations require immediate attention.

In patients with an increased risk of side effects, blood concentrations may be measured to determine the lowest possible effective dose. A therapeutic level of 60-100/150 ng/ml is recommended.

Dental checks are indicated because of the greater risk of caries.

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. Dopheide JA, Recognizing and treating depression in children and adolescents, Am J Health Syst Pharm, 2006, 63, 33-43
2. Geller B, et al, Double-blind placebo-controlled study of nortriptyline in depressed adolescents using a \"fixed plasma level\" design, Psychopharmacol Bull., 1990, 26, 85-90
3. Geller B, et al, Double-blind, placebo-controlled study of nortriptyline in depressed children using a \"fixed plasma level\" design, Psychopharmacol Bull, 1989, 25, 101-8
4. Geller B, et al, Child and adolescent nortriptyline single dose pharmacokinetic parameters: final report., J Clin Psychopharmacol, 1987, 7, 321-3
5. Prince JB, et al, A controlled study of nortriptyline in children and adolescents with attention deficit hyperactivity disorder, J Child Adolesc Psychopharmacol., 2000, 10, 193-204
6. Spencer T, et al, Nortriptyline treatment of children with attention-deficit hyperactivity disorder and tic disorder or Tourette\'s syndrome, J Am Acad Child Adolesc Psychiatry, 1993, 32, 205-10
7. Wagner KD, Pharmacotherapy for major depression in children and adolescents., Prog Neuropsychopharmacol Biol Psychiatry, 2005, 29, 819-26
8. Wilens TE, et al, Nortriptyline in the treatment of ADHD: a chart review of 58 cases, J Am Acad Child Adolesc Psychiatry, 1993, 32, 343-9
9. Wilens TE, et al, A retrospective study of serum levels and electrocardiographic effects of nortriptyline in children and adolescents., J Am Acad Child Adolesc Psychiatry., 1993, 32, 270-7
10. CBO, ADHD- Richtlijn voor de diagnostiek en behandeling van ADHD bij kinderen en jeugdigen., www.cbo.nl, 2005

Changes

Therapeutic Drug Monitoring

Overdose