A recent Drug Safety Update (DSU) has highlighted the risks of seizures and serotonin syndrome in patients prescribed tapentadol in conjunction with other drugs that either reduce the seizure threshold or have serotonergic activity.

Tapentadol

Tapentadol is an opioid analgesic initially launched in the UK in 2013. It is marketed under the brand name Palexia® and is available in the following formats:

• Oral solution 20mg/ml
• Immediate release tablets 50mg/75mg
• Modified release tablets 50mg/100mg/150mg/200mg/250mg

The licensing indications for these products varies with:

• the oral solution being licensed for relief of moderate to severe acute pain in children from 2 years of age and in adults,
• the immediate release tablets being licensed for the relief of moderate to severe acute pain in adults
• the modified release products being licensed for the management of severe chronic pain in adults [1]

In all cases tapentadol is indicated for pain that can only be adequately managed with an opioid analgesic.

Current literature advises that oral tapentadol has approximately a third of the potency of oral morphine, with 50mg oral tapentadol being approximately equivalent to 15mg oral morphine[2].

Clinical use of tapentadol in children is restricted to hospital use to ensure that adequate facilities for respiratory support are available.

Seizure Risk

The risk of seizures is a recognised adverse reaction for all opioid medicines. The use of tapentadol in patients with a history of seizure disorders or epilepsy should only be initiated with care following a risk assessment. The warnings relating to seizures have been strengthened on the relevant Summary of Product Characteristics and Patient Information Leaflets.

A recent EU review of safety data for tapentadol has highlighted that approximately 50% of spontaneous reports of seizures detailed co-administration of medicines that are recognised to reduce seizure threshold, including selective serotonin-re-uptake inhibitors (SSRIs), serotonin noradrenaline reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs) and antipsychotics.

Serotonin syndrome

Serotonin syndrome is a rare but potentially life-threatening condition associated with excessive serotonergic activity in the central and peripheral nervous systems. Serotonin syndrome can occur as a result of a single drug or combination of drugs that increase serotonergic activity.

There have been reports of serotonin syndrome linked to the use of tapentadol in combination with drugs possessing serotonergic activity such as SSRIs, SNRIs, TCAs and also antipsychotics.

Patients suffering from serotonin syndrome may initially present with anxiety, diaphoresis, and tachycardia. However, diagnostic symptoms include:

• Spontaneous clonus (involuntary, rhythmic, muscular contractions and relaxations)
• Inducible or ocular clonus (rapid and equal movements of the eyes) with agitation or diaphoresis (excessive, abnormal sweating)
• Tremor and hyperreflexia (overactive or overresponsive reflexes)
• Hypertonia (excessive muscle tone) and temperature above 38°C ,

Management of serotonin syndrome is effectively symptomatic along with withdrawal of the serotonergic medication, which usually brings about a rapid improvement. Cessation of tapentadol can result in withdrawal symptoms.

Advice for healthcare professionals

• Like 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 serotonergic antidepressants
• Withdrawal of the serotonergic medicine, together with supportive care, usually brings about a rapid improvement in serotonin syndrome
• Suspected adverse drug reactions, including those resulting from interactions, between drugs should be reported on a Yellow Card