⚠️ Warnings
A very important aspect during tapentadol therapy is its addictive potential. Individuals taking opioid receptor agonists must be continuously monitored to detect misuse without medical indication and dependence. Both the prescriber and the dispensing pharmacist should inform the patient about this phenomenon.
In cases of polypharmacy, i.e. when a patient is taking several medications simultaneously that include, in addition to tapentadol, other sedating agents such as benzodiazepines, particular caution should be exercised. Concomitant use of such preparations may lead to enhanced sedation, somnolence, respiratory depression, coma, and even death. In such cases, the doses and timing of administration 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 taking medications from the aforementioned groups.
Substances with central nervous system 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 with a history of, or confirmed, increased intracranial pressure, those in a coma, or with impaired consciousness should not use tapentadol. Patients in this risk group are continuously monitored, and this drug could mask the true clinical picture.
In individuals who experience seizures or those at increased risk, the use of tapentadol is not recommended. When taken together with other drugs that lower the seizure threshold, there is a risk of seizure occurrence. No clinical data are available on this subject, as patients with seizure disorders were excluded from clinical trials. The same applies to patients with renal impairment.
In patients with hepatic impairment, particular caution should also be exercised, especially at the start of therapy. Clinical data indicate increased systemic exposure to tapentadol compared to individuals with normal hepatic function.
Opioid receptor agonists may cause spasm of the sphincter of Oddi, which may manifest as paroxysmal pain in the right hypochondrium (hepatic colic). Patients with diagnosed pancreatic and biliary tract diseases should use tapentadol-containing preparations with particular caution.
In the case of tapentadol therapy combined with drugs that have mixed agonist-antagonist properties (e.g. pentazocine) or with partial opioid receptor agonists (e.g. buprenorphine), particular caution should be exercised due to the risk of potentiated adverse effects, which necessitates continuous patient monitoring.
Tapentadol used concomitantly with tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), antipsychotics, and other medicinal products that lower the seizure threshold may increase the risk of convulsions. Furthermore, cases of serotonin syndrome have been reported. Discontinuation of serotonergic drugs usually improved the patient's condition.
Inhibition of uridine diphosphate transferase, which is involved in the elimination pathway of tapentadol, by drugs such as fluconazole, ketoconazole, and meclofenamic acid, may result in increased systemic exposure to tapentadol.
Substances that induce uridine diphosphate transferase, such as rifampicin, phenobarbital, and St. John's wort, may decrease the efficacy of tapentadol and increase the risk of potentiated adverse effects.
Patients being treated with monoamine oxidase inhibitors or who have discontinued such drugs within the preceding 14 days should not use tapentadol due to the high risk of hypertensive crisis caused by elevated norepinephrine concentrations at the synapses.
