Tapentadol

Products

Tapentadol is approved in film-coated tablet, sustained-release tablet, and solution forms (Palexia /-retard). It was released in many countries in late February 2011 and went on sale in the fall. Tapentadol, like tramadol (Tramal, generics), was developed at Grünenthal. The sustained-release tablets were approved in 2013 and the solution went on sale in many countries in 2014.

Structure and properties

Tapentadol (C14H23NO, Mr = 221.3 g/mol) has structural similarities to tramadol but is not a racemate or a prodrug. In the drug product, it is present as tapentadol hydrochloride.

Effects

Tapentadol (ATC N02AX06) has central analgesic properties. Like opioids, it binds to μ-receptors and additionally inhibits the reuptake of norepinephrine. The corresponding drug group is therefore also referred to as MOR-NRI (“μ-opioid receptor agonists / norepinephrine reuptake inhibitors”). Tapentadol has a similar profile to tramadol, but is reported to be only weakly serotonergic. It binds to μ-receptors with a lower affinity than morphine. The half-life is short at 4 hours, which is why additional sustained-release dosage forms have been developed.

Indications

For the treatment of moderate-to-severe pain. Tapentadol is effective against nociceptive and neuropathic pain (nerve pain).

Dosage

According to the SmPC. The dose is increased slowly at the beginning of treatment and adjusted individually. Discontinuation is by slow tapering. The drug is taken with water independently of meals.

Contraindications

  • Hypersensitivity
  • Conditions in which opioids are contraindicated (e.g., respiratory depression)
  • Intestinal obstruction
  • Therapy with an MAO inhibitor
  • Epilepsy not adequately controlled by treatment.
  • Acute alcohol, drug or medication intoxication

For complete precautions, see the drug label.

Interactions

Tapentadol has marked metabolism and is almost completely biotransformed (97%). Bioavailability is only about 32% due to high first-pass metabolism. Tapentadol is mainly glucuronidated via UGT1A6, UGT1A9, and UGT2B7. A small proportion is metabolized by CYP2C9, CYP2C19, and CYP2D6. Interactions are possible via these mechanisms, but have not been observed in interaction studies and are considered unlikely. The resulting metabolites are inactive and excreted primarily via the kidneys. Unlike tramadol, it is not a prodrug. Interactions may occur in combination with MAO inhibitors, central depressant drugs, opioids, and opioid antagonists. Concomitant administration of serotonergic drugs may rarely cause serotonin syndrome.

Adverse effects

The most common adverse effects include dizziness, drowsiness, headache, nausea, and constipation. Other common adverse effects include lack of appetite, anxiety, depressed mood, sleep disturbances, nervousness, attention deficit disorder, tremor, flushing, respiratory disturbances, indigestion, weakness, fatigue, and dry mucous membranes.