Overview

Tapentadol is an opioid analgesic indicated for the management of moderate to severe chronic pain unresponsive to non-narcotic analgesia.

Background

NPRA has received information from the Medicines and Healthcare products Regulatory Agency (MHRA), United Kingdom on the risk of seizures with tapentadol use. MHRA also highlighted reports of serotonin syndrome when tapentadol was co-administered with serotonergic antidepressants.

(i) Risk of seizures

The risk of seizures is an identified adverse reaction for all opioid drugs including tapentadol. However, a recent review of safety data for tapentadol in the European Union has suggested the need for strengthened warnings on the risk of seizures.

It was found that about half of the spontaneous reports involving seizures that were identified in the review revealed a co-administration of tapentadol with one or more drugs known to lower seizure threshold. These drugs include selective serotonin-reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, and antipsychotics.

(ii) Reports of serotonin syndrome

Cases of serotonin syndrome have been reported when tapentadol is co-administered with antidepressants, such as SSRIs, SNRIs, tricyclic antidepressants and antipsychotics¹. Healthcare professionals are advised to monitor patients for signs and symptoms suggestive of serotonin syndrome (see Advice for Healthcare Professionals below).

Based on the outcome of the review, MHRA has strengthened warnings on the risk of seizure in the product information and patient information leaflets.

Adverse Drug Reaction Reports

Since it was first registered in Malaysia in 2015, no ADR reports suspected to be related to tapentadol have been received by NPRA².

Advice for Healthcare Professionals

• Like other opioid drugs, tapentadol may induce seizures.
• Care should be taken when prescribing tapentadol to patients with a history of seizure disorders or epilepsy.
• Tapentadol may increase the risk of seizures in patients who are taking other drugs that lower seizure threshold, i.e. antidepressants such as serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, and antipsychotics.
• Serotonin syndrome has been reported in patients receiving tapentadol together with serotoninergic antidepressants. Counsel patients and their caretakers to report any symptoms suggestive of serotonin syndrome such as sweating, agitation, tremor, hyper-reflexia, hypertonia, fever, spontaneous clonus (involuntary, rhythmic, muscular contraction and relaxation) and inducible ocular clonus.
• Withdrawal of serotoninergic drugs and supportive symptomatic care are recommended for a rapid improvement in serotonin syndrome.
• Please report all adverse events suspected to be related to the use of tapentadol to NPRA.

References

1. Medicines and Healthcare products Regulatory Agency (2019). Tapentadol (Palexia): Risk of seizures and reports of serotonin syndrome when co-administered with other medicines. Drug Safety Update.
2. The Malaysian Adverse Drug Reactions database, NPRA [Accessed: March 2019].

DISCLAIMER

This publication is aimed at health professionals. The information is meant to provide updates on medication safety issues, and not as a substitute for clinical judgement. While reasonable care has been taken to verify the accuracy of the information at the time of publication, the NPRA shall not be held liable for any loss whatsoever arising from the use of or reliance on this publication.