PATIENTS RECEIVING OTHER OPIOID AGONIST ANALGESICS, GENERAL ANESTHETICS, PHENOTHIAZINES, ANTIEMETICS, OTHER TRANQUILIZERS, SEDATIVES, HYPNOTICS, CENTRALLY ACTING MUSCLE RELAXANTS, OR OTHER CNS DEPRESSANTS (INCLUDING ALCOHOL) CONCOMITANTLY WITH TAPENTADAOL MAY EXPERIENCE ADDITIVE CNS DEPRESSION. THE CO-ADMINISTRATION OF ALCOHOL WITH TAPENTADAOL MAY RESULT IN INCREASED SERUM LEVELS AND A POTENTIALLY FATAL OVERDOSE OF TAPENTADOL. CONTRAINDICATED IN PATIENTS WHO ARE RECEIVING MONOAMINE OXIDASE (MAO) INHIBITORS OR WHO HAVE TAKEN THEM WITHIN THE LAST 14 DAYS DUE TO POTENTIAL ADDITIVE EFFECTS ON NOREPINEPHRINE LEVELS, WHICH MAY RESULT IN ADVERSE CARDIOVASCULAR EVENTS. IF CONCOMITANT TREATMENT OF TAPENTADAOL WITH SEROTONERGIC DRUGS LIKE SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIS), SEROTONIN AND NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIS), TRICYCLIC ANTIDEPRESSANTS (TCAS), TRIPTANS, DRUGS THAT AFFECT THE SEROTONERGIC NEUROTRANSMITTER SYSTEM (E.G. MIRTAZAPINE, TRAZODONE, AND TRAMADOL), AND DRUGS THAT IMPAIR METABOLISM OF SEROTONIN (INCLUDING MAOIS) IS CLINICALLY WARRANTED, CAREFUL OBSERVATION OF THE PATIENT IS ADVISED, PARTICULARLY DURING TREATMENT INITIATION AND DOSE INCREASES. TAPENTADAOL WITH MIXED AGONIST/ANTAGONISTS (E.G., BUTORPHANOL, NALBUPHINE, AND PENTAZOCINE) AND PARTIAL AGONISTS (E.G., BUPRENORPHINE) COULD LEAD TO A REDUCTION OF THE ANALGESIC EFFECT BY COMPETITIVE BLOCKING OF OPIOID RECEPTORS, AND/OR WITHDRAWAL. TAPENTADAOL WITH ANTICHOLINERGIC PRODUCTS MAY INCREASE THE RISK OF URINARY RETENTION AND/OR SEVERE CONSTIPATION, WHICH MAY LEAD TO PARALYTIC ILEUS.