Tapentadol: an opioid with a second pain-blocking action

The UK product information for tapentadol prolonged-release tablets states that they are indicated for the management of severe chronic pain in adults, and in children above 6 years and adolescents, that can be adequately managed only with opioid analgesics. That wording matters: it places tapentadol as a later-step treatment, not a first choice for everyday aches or short-lived pain.

It is a strong analgesic with mu-opioid agonist action and an additional noradrenaline reuptake inhibition property. It acts directly without a pharmacologically active metabolite, and clinical trials with prolonged-release tablets have verified efficacy in chronic nociceptive and neuropathic pain.

The information stresses that before starting, a treatment strategy including duration and goals and a plan for ending treatment should be agreed with the patient. The dosing regimen is individualised by pain severity, previous treatment and the ability to monitor the patient, and treatment should not be used longer than necessary. The prolonged-release tablets are taken twice daily, about every 12 hours.

For people not already taking opioids the starting dose is a single 50mg tablet twice a day, and for those switching from other opioids the initial dose takes the previous medicine and dose into account. After starting, the dose is titrated to a level giving adequate pain relief with tolerable effects.

Tolerance, physical and psychological dependence and opioid use disorder may develop with repeated use of opioids such as tapentadol, and higher doses and longer treatment raise the risk. Patients need monitoring for signs of drug-seeking behaviour, such as asking for refills too early, and clinicians should review concomitant opioids and psychoactive medicines.

Clinicians should be vigilant for withdrawal after repeated administration and avoid abrupt cessation. Never stop or change a prescribed opioid without speaking to your prescriber, who can taper the dose.

Combining tapentadol with sedating medicines such as benzodiazepines or related substances can cause sedation, respiratory depression, coma and death, so the combination is limited to situations where alternatives are not possible. Patients and carers should know to watch for breathing problems and sedation. Alcohol and other central nervous system depressants add to this effect, and acute intoxication with alcohol, hypnotics or other centrally acting analgesics is a contraindication.

Tapentadol can induce convulsions and increase the potential of SSRIs, SNRIs, tricyclic antidepressants, antipsychotics and other seizure-threshold-lowering medicines to cause them. Serotonin syndrome has been reported with serotonergic medicines, and signs include clonus, agitation, sweating, tremor, overactive reflexes, stiffness and a high temperature. Care is needed with mixed agonist-antagonist opioids and with buprenorphine, and with strong enzyme inducers such as rifampicin, phenobarbital and St John's wort.

The contraindications include hypersensitivity to tapentadol or any ingredient, situations where mu-opioid agonists are contraindicated, such as significant respiratory depression in unmonitored settings, any patient who has or is suspected of having paralytic ileus, and acute intoxication with alcohol, hypnotics, centrally acting analgesics or psychotropic substances.

Caution is needed in people susceptible to raised pressure in the skull after a head injury, with respiratory problems, and with seizure disorders. The information also says not to use the prolonged-release product for acute post-operative pain because of the risk of persistent post-operative opioid use and ventilatory impairment.

There is very limited data in pregnant women. Animal studies did not show teratogenic effects, but it should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus, and long-term maternal opioid use can lead to neonatal withdrawal. It is not recommended during or immediately before labour. A risk to a breastfed infant cannot be excluded.

It may have a major influence on the ability to drive and use machines. Reactions listed include dizziness, drowsiness and headache (common), nausea and constipation, with less common effects including anxiety, confusion, tremor, palpitations and flushing, and rarer ones including convulsion and drug dependence. Seek help promptly for slowed breathing, confusion or seizures.