⚠️ Warnings
A very important aspect of tapentadol therapy is its addictive potential. Patients taking opioid receptor agonists must be continuously monitored to detect any non-medical misuse or dependence. Both the prescriber and the dispensing pharmacist should inform the patient about this risk.
In cases of polypharmacy, i.e. when a patient takes multiple medications simultaneously and the medication list includes, in addition to tapentadol, other sedating drugs such as benzodiazepines, particular caution should be exercised. Concomitant use of these agents may lead to enhanced sedation, somnolence, respiratory depression, coma, and even death. In such cases, the doses and timing of the medications should be reviewed, or alternative treatment methods should be considered to avoid potentiated adverse effects. It is important to inform the patient about this effect of combining medications from these drug classes.
Substances with CNS or respiratory depressant effects, such as benzodiazepines, antipsychotics, other opioids, antitussives, H1 antihistamines, barbiturates, and alcohol, when used concomitantly with tapentadol, increase the risk of coma and even death due to cumulative CNS depressant effects. Excessive sedation and respiratory depression may occur.
Patients with head injuries and those with a history of risk for or confirmed increased intracranial pressure, those in a comatose state, or with altered consciousness should not use tapentadol. Patients in this risk group require continuous monitoring, and the drug could mask the true clinical picture.
Tapentadol is not recommended in patients with seizure disorders or those at increased risk of seizures. When taken with other medicinal products that lower the seizure threshold, there is a risk of seizure occurrence. No clinical data are available on this topic, as patients with seizure disorders were excluded from clinical trials. The same applies to patients with renal impairment.
Particular caution should also be exercised in patients with hepatic impairment, especially at the beginning of therapy. Clinical data indicate increased systemic exposure to tapentadol compared to patients with normal hepatic parameters.
Opioid receptor agonists may cause spasm of the sphincter of Oddi, which may present as paroxysmal pain in the right hypochondrium (hepatic colic). Patients with known pancreatic and biliary tract diseases should use tapentadol-containing preparations with particular caution.
Particular caution should be exercised when tapentadol is used concomitantly with drugs possessing mixed agonist-antagonist properties (e.g. pentazocine) or partial opioid receptor agonists (e.g. buprenorphine), due to the risk of potentiated adverse effects requiring continuous patient monitoring.
Concomitant use of tapentadol with tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs), antipsychotics, and other medicinal products that lower the seizure threshold may increase the risk of seizures. Furthermore, cases of serotonin syndrome have been reported. Discontinuation of the serotonergic agents generally improved the patient's condition.
Inhibition of uridine diphosphate transferase, which is involved in the elimination pathway of tapentadol, by agents such as fluconazole, ketoconazole, and meclofenamic acid, may lead to increased systemic exposure to tapentadol.
Substances that induce uridine diphosphate transferase, such as rifampicin, phenobarbital, and St John's wort, may reduce the efficacy of tapentadol and increase the risk of potentiated adverse effects.
Patients treated with monoamine oxidase inhibitors or those who have discontinued MAOIs within the preceding 14 days should not use tapentadol, due to a high risk of hypertensive crisis caused by increased noradrenaline concentrations in the synaptic cleft.
