Published: 4 June 2020

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Spotlight on tramadol, including updated advice for use in children

Prescriber Update 41(2): 25–26
June 2020

This article informs healthcare professionals of updated advice on the use of tramadol in children. It is also a reminder of tramadol’s metabolism, use in patients aged over 75 years, and some serious adverse reactions.

What is tramadol?

Tramadol is a centrally-acting synthetic analgesic that exerts its effect by^1,2:

• binding to μ-opioid receptors
• inhibiting the reuptake of noradrenaline and serotonin.

Tramadol is used to relieve moderate to severe pain when paracetamol and/or a non-steroidal anti-inflammatory drug (NSAID) is not adequate^1,2.

The importance of CYP2D6

Tramadol is similar to codeine in that CYP2D6 is important for producing metabolites that have a greater affinity for the μ-opioid receptor than the parent drug³.

Tramadol’s principal active metabolite is O-desmethyltramadol (M1)¹. Animal models show M1 to be six-times more potent than tramadol in producing analgesia and 200 times more potent in μ-opioid binding¹.

Patients with a deficiency of CYP2D6 may have reduced benefit from tramadol³. On the other hand, patients who are ultra-rapid metabolisers may be more sensitive to adverse reactions, even at commonly prescribed doses³. The frequency of poor metaboliser and ultra-rapid metaboliser phenotypes varies between populations⁴.

Tramadol is contraindicated in children

Following review of their safety data, the companies have now contraindicated the use of tramadol in:

• children aged under 12 years
• children aged under 18 years for post-operative pain management following tonsillectomy and/or adenoidectomy.

The tramadol data sheets are in the process of being updated with these contraindications.

Use with caution in patients aged over 75 years

Serum concentrations of tramadol are slightly elevated, and the elimination half-life is slightly prolonged in patients aged over 75 years¹. Their tolerance of adverse reactions is expected to vary more widely. Therefore, use a lower maximum daily dose of 300 mg in these patients¹.

Serious adverse reactions

Tramadol is associated with adverse reactions seen for both opioid and antidepressant medicines². Tramadol should be administered cautiously in patients at risk of respiratory depression¹. Avoid concomitant use with benzodiazepines or other central nervous system (CNS) depressants unless there are no suitable alternative treatment options¹.

Tramadol may cause serotonin syndrome when taken alone or if the dose is increased, and more frequently when taken with another serotonergic medicine. Avoid concomitant use with selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants and mirtazapine. For more information about serotonin syndrome, see the September 2015 edition of Prescriber Update.

Seizures have been reported in patients taking tramadol even at the recommended dose¹. Tramadol may also increase the seizure risk in patients taking other medicines that lower the seizure threshold¹. Avoid using tramadol in patients with epilepsy or those susceptible to seizures.

Please refer to the medicine data sheet for full prescribing information.

Adverse reactions reported in New Zealand over the last five years

The Centre for Adverse Reactions Monitoring (CARM) has received 83 adverse reaction reports relating to tramadol from 1 January 2015 to 31 December 2019. The most frequently reported reactions were rashes (12), vomiting (10) and nausea (9).

Serotonin syndrome was reported in five cases (CARM IDs: 115985, 116267, 121427, 129817, 134414). Four of these cases reported a SSRI or SNRI as co-suspects. Convulsions were reported in five cases (CARM IDs: 121427, 124017, 129062, 129605, 133745).

Of the 83 reports, six were in children aged under 12 years and seven were in patients aged over 75 years.

References

1. Seqirus (NZ) Ltd. 2018. Tramal New Zealand Data Sheet December 2019. URL: medsafe.govt.nz/profs/Datasheet/t/TramalcapSRtabinjoraldrops.pdf (accessed 21 April 2020).
2. BPAC NZ. 2018. Prescribing tramadol appropriately 23 February 2018. URL: bpac.org.nz/2018/tramadol.aspx (accessed 17 April 2020).
3. Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine. 2015. Acute Pain Management: Scientific Evidence (Fourth edition). URL: fpm.anzca.edu.au/documents/apmse4_2015_final (accessed 17 April 2020).
4. Medsafe. 2018. Spotlight on codeine. Prescriber Update 39(2): 18–19. URL: medsafe.govt.nz/profs/PUArticles/June2018/SpotlightOnCodeine.htm (accessed 23 April 2020).