Tapentadol (Palexia): risk of seizures and reports of serotonin syndrome when co-administered with other medicines

Tapentadol may increase seizure risk in patients taking other medicines that lower seizure threshold, for example, antidepressants and antipsychotics. Serotonin syndrome has also been reported when tapentadol is used in combination with serotoninergic antidepressants.

Advice for healthcare professionals:

  • as for all opioid medicines, tapentadol can induce seizures
  • tapentadol should be prescribed with care in patients with a history of seizure disorders or epilepsy
  • tapentadol may increase seizure risk in patients taking other medicines that lower seizure threshold, for example, antidepressants such as serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs), tricyclic antidepressants, and antipsychotics
  • serotonin syndrome has been reported when tapentadol is used in combination with serotoninergic antidepressants (see typical presenting symptoms below)
  • withdrawal of the serotoninergic medicine, together with supportive symptomatic care, usually brings about a rapid improvement in serotonin syndrome
  • report suspected adverse drug reactions, including those resulting from interactions between drugs, on a Yellow Card

Background

Tapentadol (Palexia) is an opioid analgesic authorised for the relief of acute moderate to severe pain that can only be adequately managed with opioid analgesics in adults and children aged 2 years and older. Tapentadol is also indicated in adults only for the management of severe chronic pain that can be adequately managed only with opioid analgesics. See the Summary of Product Characteristics for restrictions in children, including a maximum duration of use of 3 days.

Review of data for seizure risks

The risk of seizures is a recognised adverse reaction for all opioid medicines. However, a recent review of safety data for tapentadol in the EU identified the need for strengthened advice about the risk of seizures.

Approximately half of the identified spontaneous reports of seizure reflected co-administration of tapentadol with at least one other drug known to lower seizure threshold. These medicines include selective serotonin-reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, and antipsychotics.

Tapentadol should be used with care in patients with a history of seizure disorders or epilepsy because of the increased risk of seizures. Strengthened warnings on seizure risk have been added to the Summary of Product Characteristics and Patient Information Leaflets.

Reports of serotonin syndrome

We are also aware of reports of serotonin syndrome identified when tapentadol is co-administered with antidepressants, such as serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs), tricyclic antidepressants and antipsychotics.

Serotonin syndrome is likely when one of the following is observed:

  • Spontaneous clonus
  • Inducible or ocular clonus with agitation or diaphoresis (sweating)
  • Tremor and hyper-reflexia
  • Hypertonia and body temperature higher than 38°C and inducible ocular clonus

Withdrawal of the serotoninergic medicine together with supportive symptomatic care, usually brings about a rapid improvement. The continued use of tapentadol must be evaluated on an ongoing basis. Withdrawal symptoms can occur with abrupt cessation of treatment.

See the Summary of Product Characteristics for tapentadol for details of other interactions, including advice to avoid monoamine oxidase inhibitors with tapentadol because of the potential for hypertensive crisis.

Report any suspected adverse drug reactions

Please continue to report suspected adverse drug reactions (ADRs), including interactions between medicines, on a Yellow Card. Reporting suspected ADRs, even those known to occur in association with the medicine, adds to knowledge about the frequency and severity of these reactions and can be used to identify patients who are most at risk. Your report helps the safer use of medicines.

Healthcare professionals, patients, and caregivers can report suspected ADRs via the Yellow Card website or via the Yellow Card app. Download the app today via iTunes Yellow Card for iOS devices or via PlayStore Yellow Card for Android devices.

Article citation: Drug Safety Update volume 12, issue 6: January 2019: 1.

Published 9 January 2019
Last updated 9 January 2019 + show all updates
  1. Re-published.
  2. First published.