Pharmacokinetics in children

After a single administration of 5 mg, the Cmax is on average 11.5 ng/ml (SmPC of Amfexa)
Tmax: 1.5-4 hours.  
T½: 6-10.2 hours (SmPC of Amfexa, Brown 1979)

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

Very common (> 10%): reduced appetite, reduced weight gain and weight loss on long-term used. Sleeplessness, nervousness.

Common (1-10%): arrhythmia, heart palpitations, tachycardia. Abdominal pain and/or cramps, nausea, vomiting, dry mouth. Changes in blood pressure (usually an increase of 2-4 mmHg) and heart rate (usually an increase of 3-6 bpm). Arthralgia. Vertigo, dyskinesia, headaches, hyperactivity. Abnormal behaviour, aggression, excitement, anorexia, anxiety, depression, irritability.

Rare (0.01-0.1%): angina pectoris. Reduced visual accommodation, vision disorders, blurred vision, mydriasis. Fatigue. Monitor growth retardation in long-term use. Rash, urticaria.

Very rare (< 0.01%): anaemia, leukopenia, thrombocytopenia, thrombocytopenic purpura. Cardiac arrest. Tourette syndrome. Abnormal hepatic function, increased liver enzyme values, hepatic coma. Muscle cramps. Convulsions, choreoathetotic movements, intracranial bleeding. Hallucinations, psychosis, tics, exacerbation of existing tics, suicide (suicidal behaviour), cerebral vasculitis and/or occlusion. Exfoliative dermatitis, erythema multiforme, fixed drug eruption.

Also reported: Raynaud's phenomenon. Cardiomyopathy, myocardial infarction. Ischemic colitis, diarrhea. Chest pain, hyperpyrexia, fatigue, sudden death. Hypersensitivity reactions such as angioedema, anaphylactic reactions. Acidosis. Rhabdomyolysis. Ataxia, dizziness, dysgeusia, concentration problems, hyperreflexia, stroke, tremor. Neuroleptic malignant syndrome. Emotional lability, confusion, dependence, dysphoria, euphoria, impaired cognitive test performance, altered libido, night terrors, obsessive-compulsive behavior, panic attacks, paranoia, restlessness. Kidney damage. Impotence. Sweating, alopecia. Cardiovascular collapse. Toxic hypermetabolic status (characterized by: transient hyperactivity, hyperpyrexia, acidosis and death from cardiovascular collapse).

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

Treatment should be under the supervision of a doctor specializing in behavioural disorders in children and/or adolescents.

The following are indicated before the start of treatment: an assessment of the cardiovascular status, including blood pressure and heart rate, sudden cardiac/unexplained death or ventricular arrhythmia in the family history; psychological disorders or symptoms (in the history); a record of height and weight on a growth chart. Do not use in cardiovascular conditions, unless cardiac advice was given by the paediatrician. When symptoms occur during the treatment that point to cardiac disease, immediately get a specialist cardiologist to evaluate. Be careful in underlying medical conditions where an increase in blood pressure or heart rate can be dangerous.

During treatment, monitor growth (height, weight, appetite), mental state (development or worsening of pre-existing psychiatric disorders) and cardiovascular status (blood pressure, pulse) at least once every six months and after each dose adjustment. Pause the treatment if growth retardation is suspected.

Stop the treatment immediately if there are signs of cerebral vasculitis (severe headaches, numbness, weakness, paralysis, impairments to coordination, vision, speech, language or memory). It might also need to be stopped in cases of the occurrence or exacerbation of psychological disorders, suicidal tendencies, increased epileptic seizures, leukopenia, thrombocytopenia, anaemia, indications of impaired renal or hepatic function. If undesired behavioural changes occur, consider changing the dose or pausing the treatment.

Be aware inter alia of the following psychiatric disorders: tics, aggressive behaviour, agitation, anxiety/depression, psychosis, bipolar disorder, mania, delusions, irritability, lack of spontaneity, retreating into themselves and excessive perseveration. Dextroamphetamine can exacerbate behavioural and thought disorders in psychotic patients. Patients with bipolar disorder may experience a mixed/-manic episode. Be aware of the likelihood of fraud, incorrect use and misuse and the use of dextroamphetamine for leisure purposes. Chronic misuse can lead to habituation and dependency with varying degrees of abnormal behaviour. Be careful in emotionally instable patients, where there is a medical history of risk factors for dependency on medicines or alcohol.

Stopping or lowering the use of amphetamine can cause withdrawal symptoms (dysphoric mood, fatigue, realistic and unpleasant dreams, sleeplessness or excessive sleeping, increased appetite, psychomotor deterioration or agitation, anhedonia and desire for the medicine). Careful monitoring is needed after stopping. This drug can increase eye pressure due to pupil dilation and trigger an attack of acute glaucoma.

Using it can result in reduced capacity to react and concentrate. This can hinder numerous day-to-day activities (e.g. driving/being in traffic).

The consequences for safety and effectiveness are completely unknown in the long term.

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

• NERVOUS SYSTEM
• PSYCHOANALEPTICS

PSYCHOSTIMULANTS, AGENTS USED FOR ADHD AND NOOTROPICS

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. Efron D, et al, Methylphenidate versus dexamphetamine in children with attention deficit hyperactivity disorder: A double-blind, crossover trial., Pediatrics, 1997, 100(6), E6
2. Efron D, et al., Side effects of methylphenidate and dexamphetamine in children with attention deficit hyperactivity disorder: a double-blind, crossover trial, Pediatrics, 1997, 100(4), 662-666
3. No author listed, National Institute of Mental Health Multimodal Treatment Study of ADHD follow-up: changes in effectiveness and growth after the end of treatment, Pediatrics, 2004, 113(4), 762-9
4. Landelijke Stuurgroep Multidisciplinaire Richtlijnontwikkeling (LSMR), Multidisciplinaire richtlijn ADHD- Richtlijn voor de diagnostiek en behandeling van ADHD bij kinderen en jeugdigen., www.nvk.nl, 2005
5. MEDICE Arzneimittel Pütter GmbH & Co. KG, SmPC Amfexa (RVG 110336) 10-02-2016, www.geneesmiddeleninformatiebank.nl
6. Brown GL et al., Plasma levels of d-amphetamine in hyperactive children. Serial behavior and motor responses., Psychopharmacology (Berl)., 1979, Apr 11;62(2), 133-40
7. Elia J et al., Methylphenidate and dextroamphetamine treatments of hyperactivity: are there true nonresponders?, Psychiatry Res., 1991, Feb;36(2), 141-55
8. Pelham WE et al., A comparison of morning-only and morning/late afternoon Adderall to morning-only, twice-daily, and three times-daily methylphenidate in children with attention-deficit/hyperactivity disorder., Pediatrics., 1999, Dec;104(6), 1300-11
9. Short EJ et al., A prospective study of stimulant response in preschool children: insights from ROC analyses., J Am Acad Child Adolesc Psychiatry., 2004, Mar;43(3):, 251-9
10. Eysbouts Y et al., Stimulant medication in pre-school children in New South Wales., J Paediatr Child Health., 2011, Dec;47(12):, 870-4
11. National Collaborating Centre for Mental Health., Attention Deficit Hyperactivity Disorder: Diagnosis and Management of ADHD in Children, Young People and Adults., Leicester (UK): British Psychological Society (UK), 2009
12. Government of Western Australia, department of health., Stimulant Prescribing Code Clinical criteria for the prescribing of stimulant medicines in Western Australia., www.public.health.wa.gov.au
13. Lareb. , Dexamfetamine en het fenomeen van Raynaud. , www.lareb.nl , 13-1-2017. , https://www.lareb.nl/nl/news/dexamfetamine-en-het-fenomeen-van-raynaud/
14. Medice, SmPC Attentin 10 mg/20 mg Tabletten (74643.00.00), 01/2016
15. Medice, SmPC Attentin 5 mg Tabletten (74643.00.00), 01/2016
16. DAC/NRF, Dexamfetaminsulfat-Tropfen 25 mg/ml (NRF 22.9.), NRF 2017-1
17. Lareb., Dexamfetamine en het fenomeen van Raynaud., www.lareb.nl, 13-1-2017., https://www.lareb.nl/nl/news/dexamfetamine-en-het-fenomeen-van-raynaud/

Changes

Therapeutic Drug Monitoring

Overdose