Tapentadol

Tapentadol is a centrally acting analgesic combining mu-opioid agonism with noradrenaline reuptake inhibition. It is used for moderate to severe acute and chronic pain, including neuropathic components. It has no active metabolites and little cytochrome-mediated interaction, but it retains the full class risks of an opioid.

Class. Strong opioid analgesic (mu agonist and noradrenaline reuptake inhibitor).

Mechanism. Mu receptor agonism, with potency about 18 times lower than morphine at the receptor, plus inhibition of noradrenaline reuptake that adds to analgesia in neuropathic pain.

Pharmacokinetics. Oral bioavailability about 32% because of first-pass metabolism. Onset 30 minutes, peak 1.25 hours, duration 4 to 6 hours (12 hours for extended release). Half-life about 4 hours. Metabolised by glucuronidation to inactive metabolites; minimal CYP involvement; renal excretion.

Indications are moderate to severe acute pain and severe chronic pain, including painful diabetic peripheral neuropathy (extended release).

Adults

• Immediate release: 50 mg every 4 to 6 hours (50, 75 or 100 mg each dose). Maximum 600 mg in 24 hours; maximum 700 mg on day 1 if a second dose is given 1 hour after the first.
• Extended release: start 50 mg every 12 hours in opioid-naive patients. Increase by 50 mg twice daily every 3 days. Usual effective range 100 to 250 mg every 12 hours. Maximum 500 mg daily.
• Conversion from other opioids is imprecise; start at a low dose and titrate.
• Diabetic peripheral neuropathy pain: extended release, 50 mg twice daily, titrate to 100 to 250 mg twice daily.

Children. Not advised under 18 years.

Conversion. Roughly 50 mg of tapentadol is equal to 20 to 25 mg of oral morphine.

Contraindications. Respiratory depression without ventilatory support; acute severe asthma; paralytic ileus; monoamine oxidase inhibitor within 14 days; hypersensitivity; severe hepatic impairment.

Boxed-warning-level risks. Addiction, abuse and misuse; life-threatening respiratory depression; accidental exposure; neonatal opioid withdrawal syndrome; concurrent benzodiazepines and other depressants; serotonin syndrome and seizures.

Adverse effects. Common: nausea, vomiting, constipation (less than with equianalgesic morphine), dizziness, drowsiness, headache, pruritus. Serious: respiratory depression, seizures, serotonin syndrome, hypotension, urinary retention and opioid use disorder.

Interactions. Serotonergic drugs (SSRIs, SNRIs, tricyclic antidepressants, triptans, linezolid) increase serotonin syndrome and seizure risk. Monoamine oxidase inhibitors are contraindicated. Additive sedation with benzodiazepines, alcohol and gabapentinoids. Few pharmacokinetic interactions.

Common prescribing errors. Treating the dose as equal to oral tramadol or morphine; exceeding the daily maximum; adding it to an antidepressant without risk review; using in people with seizure disorders; rapid titration of extended release.

Special groups

• Pregnancy: avoid; neonatal withdrawal and respiratory depression.
• Breastfeeding: avoid.
• Older adults: start at the lowest dose.
• Kidney impairment: mild to moderate, no adjustment; severe (creatinine clearance under 30 mL/min), not advised.
• Liver impairment: moderate (Child-Pugh B), immediate release 50 mg no more often than every 8 hours (maximum 3 doses in 24 hours), extended release 50 mg once daily with a maximum of 100 mg daily; avoid in severe disease.
• Regional: availability is limited; confirm the formulation stocked.

Formulations. Immediate-release tablets (50, 75, 100 mg), extended-release tablets (50 to 250 mg), oral solution in some markets.

Administration. Oral doses with or without food. Swallow extended-release tablets whole. Do not crush or chew.

Baseline. Seizure history, concurrent serotonergic drugs, hepatic and renal function, opioid exposure history and respiratory status.

Monitoring. Pain, nausea, sedation, respiratory rate and mental state. Review after 1 to 2 weeks of a stable dose. Bowel function.

Therapeutic drug monitoring. Not used.

Dose reduction and stopping thresholds. Stop for seizures or serotonin syndrome. Reduce for excessive sedation or respiratory rate under 10 breaths/minute. After more than 1 week of regular use, reduce by 10 to 25% every few days.

Referral and escalation. Respiratory depression or serotonin syndrome needs emergency care. Persistent need after 3 months warrants specialist pain review.