Amitriptyline

Generic name
Amitriptyline
Brand name
ATC Code
N06AA09
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Amitriptyline

Dosages
Side effects in children
Warnings & precautions in children
Contra-indications in children

Interactions
PK
Renal impairment
References

Pharmacokinetics in children

There is no data available about the pharmacokinetics in children.

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

Nocturnal enuresis
  • Oral
    • Normal preparation (immediate release)
      • 6 years up to 18 years
        [1] [12]
        • (amitriptyline hydrochloride) 1 - 1.5 mg/kg/day in 1 dose. Max: 50 mg/day.
          • The dose should be increased gradually.
          • Doses should be administered 1-1.5 hours before going to bed.
          • Length of treatment: max. 3 months. If repeated cycles are necessary, a medical assessment should be made every 3 months.
          • Treatment with amitriptyline must not be stopped suddenly because withdrawal symptoms can occur; the dosage must be reduced gradually.
    • Extended release tablet
      • ≥ 11 years
        [2]
        • (amitriptyline hydrochloride) 25 - 50 mg/day in 1 dose
Neuropathic pain
  • Oral
    • 6 years up to 18 years
      [3] [4] [5] [6] [7]
      • (amitriptyline hydrochloride) Initially: 5 - 10 mg/day in 1 dose for the night. If necessary, increase slowly to max. 25 mg/day.

      • Treatment with amitriptyline must not be stopped suddenly because withdrawal symptoms can occur; the dosage must be reduced gradually.
Headache (prophylaxis)
  • Oral
    • 6 years up to 18 years
      [8] [9] [10] [11] [13]
      • Initial dose: (amitriptyline hydrochloride)
        for the night: 10         mg/day in 1 dose
      • Maintenance dose: increase slowly by 10 mg/day every 4-6 weeks to 10 - 30 mg/day in 1 dose. Max: 30 mg/day.
        • Treatment with amitriptyline must not be stopped suddenly because withdrawal symptoms can occur; the dosage must be reduced gradually.
        • The study by Powers (2017) shows that the effectiveness of amitriptyline in migraine prophylaxis is no more effective than a placebo. Despite that, experts believe that treatment with amitriptyline can be considered in individual cases.

         

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

If severe side effects occur of if there is no effect, it is possible that the metabolization of the drug may be different. CYP2D6 can determine the variation in response. Genotyping can be considered.

In nocturnal enuresis, the most frequent side effects are sleepiness, anticholinergic effects, slight transpiration and itching.

In one case (n=1) of nocturnal enuresis, the reversible side effect esotropia (cross-eyed) was reported [Eidlitz-Markus et al. 2012]. In one study (n=45) of severe migraines, the side effect ‘fainting’ (n=1) was reported. In another study (n=144) of migraines, the side effect ‘mood changes’ (n=3) was reported [Powers et al. 2017].

 

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. Suicidal thoughts and behaviour can also occur during early treatment with antidepressants for conditions other than depression. 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. Suicidal thoughts and behaviour can also occur during early treatment with antidepressants for conditions other than depression. The same precautions as with the treatment of patients with depression should therefore be taken when treating patients with nocturnal enuresis, neuropathic pain or headache (prophylaxis). 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 vulnerability 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.

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

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. Apotex Europe BV, SmPC Amitriptyline (RVG 52186) 01-09-2016, www.geneesmiddeleninformatiebank.nl
  2. Lundbeck BV, SmPC Sarotex retard (RVG 06480) 18-05-2017, www.geneesmiddeleninformatiebank.nl
  3. Lauder GR et al, Neuropathic pain following multilevel surgery in children with cerebral palsy: a case series and review, Paediatr Anaesth, 2005 , May;15(5), 412-20
  4. WHO Press World Health Organization, WHO Guidelines on the Pharmacological Treatment of Persisting Pain in Children with Medical Illnesses., 2012, ISBN 978 92 4 154812 0
  5. Friedrichsdorf SJ et al. . , Management of neuropathic pain in children with cancer, Curr Opin Support Palliat Care., 2013 , Jun;7(2), 131-8
  6. Brown S et al. , A randomized controlled trial of amitriptyline versus gabapentin for complex regional pain syndrome type I and neuropathic pain in children. , Scand J Pain., 2016 , Oct;13, 156-163
  7. Anghelescu DL et al, Prospective study of neuropathic pain after definitive surgery for extremity osteosarcoma in a pediatric population., Pediatr Blood Cancer , 2017, Mar;64(3)
  8. Hershey AD et al, Effectiveness of amitriptyline in the prophylactic management of childhood headaches., Headache, 2000, 40, 539-49
  9. Eidlitz-Markus T et al, Nonpharmacologic treatment of migraine with low-dose propranolol or amitriptyline., Pediatr Neurol , 2012, 46(6), 345-9
  10. Powers SW et al. , Trial of amitriptyline, topiramate and placebo for pediatric migraine. , N Engl J Med , 2017, 376(2), 115-24
  11. Sezer T et al. , A randomized trial comparing amitriptyline versus topiramate for the prophylaxis of chronic daily headache in pediatric patients. , Int J Neurosci, 2013, 123(8), 553-6
  12. Burke JR et al, A comparison of amitriptyline, vasopressin and amitriptyline with vasopressin in nocturnal enuresis, Pediatric Nephrology , 1995, 9(4), 438-40
  13. Kinderneurologen MVKN, Expert opinie toepassing amitriptyline bij hoofdpijn., 17-4-2018.

Changes

Therapeutic Drug Monitoring


Overdose