Pharmacokinetics in children

A pharmacokinetic study (N=10, 11.5 –16.2 years) has shown that the Tmax of the extended release (XR) tablets (= average 4.8 ± 2.0 hours) is higher than the Tmax of the sustained release (SR) tablets (= average of 3.4 ± 1.6 hours). This study also shows that the Cmax of the XR tablets is lower than the Cmax of SR tablets (62 ± 26 ng/ml and 88 ± 26 ng/ml respectively).

Metabolization: in the liver to inter alia the active metabolites hydroxybupropion (mainly via CYP2B6) and threohydrobupropion and erythrohydrobupropion (not via CYP enzymes). Elimination: mainly with the urine, primarily as metabolites.

Another pharmacokinetic study (N=19, 11–17 years) showed that the elimination half-life of bupropion SR in adolescents (= 12.1 ± 3.3 hours) is shorter than in adults (= 21 ± 9 hours). The elimination half-life of the key active metabolite hydroxybupropion is approximately 21.8 ± 6.6 hours. The elimination half-lives of threohydrobupropion and erythrohydrobupropion are longer (at 26.3 ± 11.9 hours and 32.7 ± 16.0 hours respectively). This study also found that bupropion and its active metabolites exhibit linear pharmacokinetics.

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

Convulsions, restlessness, agitation, tremor, sleeplessness, headache, dizziness, concentration disorders, depression, gastrointestinal disorders (such as nausea, vomiting, abdominal pain and obstipation), dry mouth, taste disturbances, fever, transpiration, acute exanthema, itching, urticaria, anorexia.

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 convulsions and/or reduced convulsion thresholds; monitor patients closely and high-risk patients in particular (suicidal thoughts, suicide attempts) due to the increased risk of suicide.
Using it can result in reduced capacity to react and concentrate. This can hinder numerous day-to-day activities.
Bupropion should be stopped and not started again in patients who get a convulsion during a treatment. Caution is also needed in conditions that predispose towards a lowered convulsion threshold, such as head injuries in the previous history, alcohol abuse, treated diabetes mellitus, use of appetite stimulants or suppressants.
Administration in bipolar disorders can induce a manic phase during the depressed phase of the illness. If there is a known psychiatric illness in the medical history, there is an increased risk of psychotic and manic symptomatology.
Screening for suicide risks and bipolar disorder 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.

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. Daviss WB, et al., Bupropion sustained release in adolescents with comorbid attention-deficit/hyperactivity disorder and depression, J Am Acad Child Adolesc Psychiatry., 2001, 40, 307-14
2. Daviss WB, et al, Steady-state clinical pharmacokinetics of bupropion extended-release in youths, J Am Acad Child Adolesc Psychiatry., 2006, 45, 1503-9
3. Daviss WB, et al, Acute antidepressant response and plasma levels of bupropion and metabolites in a pediatric-aged sample: an exploratory study, Ther Drug Monit, 2006, 28, 190-8
4. Daviss WB, et al, Steady-state pharmacokinetics of bupropion SR in juvenile patients, J Am Acad Child Adolesc Psychiatry, 2005, 44, 349-57
5. CBO, ADHD- Richtlijn voor de diagnostiek en behandeling van ADHD bij kinderen en jeugdigen., www.cbo.nl, 2005

Changes

Therapeutic Drug Monitoring

Overdose