Pharmacokinetics in children

Metabolization: in the liver via CYP3A4, CYPC19 and CYP1A2 to the active compound desmethylclomipramine and then hydroxylation of clomipramine and desmethylclomipramine via CYP2D6.

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

CYP2D6-polymorphism may be involved in cases of strikingly numerous or severe side effects.

Sedation, sleep disorders, dry mouth (sometimes causing more caries), sweating, weight gain, obstipation, diarrhoea, nausea, dizziness, agitation, tremor, myocloni, increased appetite, accommodation disorders, urinary disorders, sinus tachycardia, palpitations, changes to the ECG, arrhythmias, conduction disorders and torsade de pointes.

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, exacerbated anxiety disorders in the first weeks; 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.

Increases in anxiety disorders can appear during the first weeks of the treatment.

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 given, attention must be paid to any cardiac problems in the patient and their family, as this group of drugs can worsen or expose existing or hereditary susceptibility to arrhythmia. The blood pressure, pulse rate and ECG need to be checked before and during the treatment. For the ECG, the main concerns are PR, QT and QRS extension. Because of these cardiac side effects, symptoms such as dizziness and heart palpitations require immediate attention. The American recommendation to measure the blood levels when using classical antidepressants about 5 days after each change of dosage was not adopted in the Netherlands.

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. Flament MF, et al, Clomipramine treatment of childhood obsessive-compulsive disorder. A double-blind controlled study., Arch Gen Psychiatry, 1985, 42, 977-83
2. DeVeaugh-Geiss J, et al, Clomipramine hydrochloride in childhood and adolescent obsessive-compulsive disorder--a multicenter trial., J Am Acad Child Adolesc Psychiatry., 1992, 31, 45-9
3. de Haan E, et al, Behavior therapy versus clomipramine for the treatment of obsessive-compulsive disorder in children and adolescents, J Am Acad Child Adolesc Psychiatry, 1998, 37, 1022-9
4. Geller DA, et al, Which SSRI? A meta-analysis of pharmacotherapy trials in pediatric obsessive-compulsive disorder., Am J Psychiatry, 2003, 160, 1919-28
5. Leonard HL, et al, Electrocardiographic changes during desipramine and clomipramine treatment in children and adolescents, J Am Acad Child Adolesc Psychiatry, 1995, 34, 1460-8
6. Leonard HL, et al, Treatment of obsessive-compulsive disorder with clomipramine and desipramine in children and adolescents. A double-blind crossover comparison, Arch Gen Psychiatry, 1989, 46, 1088-92
7. Novartis Pharma BV, SmPC Anafranil (RVG 06353) 07-07-2015, www.geneesmiddeleninformatiebank.nl
8. Ketelaars, K, Antidepressiva, Kenniscentrum KJP, http://www.kenniscentrum-kjp.nl/index.php?id=584 (21 jan 2009)

Changes

Therapeutic Drug Monitoring

Overdose