⚠️ Warnings
A very important consideration during tapentadol therapy is its addictive potential. Patients taking opioid receptor agonists must be continuously monitored to detect any non-medical misuse or dependence. Both prescribers and dispensers should inform the patient about this risk.
In cases of polypharmacy, i.e., when a patient is taking multiple medications concurrently, including sedative agents such as benzodiazepines in addition to tapentadol, 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 of concomitant medications and timing of administration should be reviewed, or alternative treatment methods should be considered to avoid potentiated adverse effects. It is essential to inform the patient about the effects of combining medications from the above-mentioned groups.
Central nervous system or respiratory depressant substances, 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 a history of or confirmed elevated intracranial pressure, those in a coma, or those with impaired consciousness should not use tapentadol. Patients in this risk group are continuously monitored, and this drug could obscure the true clinical picture.
In patients with seizure disorders or those at increased risk of seizures, the use of tapentadol is not recommended. When taken with other drugs that lower the seizure threshold, there is a risk of seizure occurrence. There are no clinical data 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 initiation 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 known pancreatic or biliary tract diseases should use tapentadol-containing products with particular caution.
In the case of tapentadol therapy combined with drugs possessing mixed agonist-antagonist properties (e.g., pentazocine) or with partial opioid receptor agonists (e.g., buprenorphine), particular caution should be exercised due to the potential for intensified adverse effects, which requires 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 seizures. Furthermore, serotonin syndrome has been reported. Discontinuation of serotonergic agents generally improved the patient's condition.
Inhibition of uridine diphosphate transferase, involved in the elimination pathway of tapentadol, by drugs such as fluconazole, ketoconazole, or meclofenamic acid, may result in increased systemic exposure to tapentadol.
Substances that induce uridine diphosphate transferase, such as rifampicin, phenobarbital, or St. John's wort, may decrease the efficacy of tapentadol and increase the risk of intensified adverse effects.
Patients currently treated with monoamine oxidase inhibitors (MAOIs) or who have discontinued MAOI therapy less than 14 days prior should not use tapentadol due to the high risk of hypertensive crisis caused by elevated norepinephrine concentrations at the synapses.
