Interaction between Tramadol and Asenapine
Major Synergy

ID DDInter1841 and DDInter125
Interaction Asenapine may cause dose-related prolongation of the QT interval. Tramadol may also prolong the QT interval, and theoretically, coadministration of multiple agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. Concomitant use of opioids such as tramadol with other central nervous system (CNS) depressants such as asenapine may result in hypotension, profound sedation, respiratory depression, coma, and death.
Management Coadministration of asenapine with tramadol should generally be avoided. If coadministration is necessary, the dosage and duration of each drug should be limited to the minimum required to achieve the desired clinical effect. Patients should have regular ECGs and be monitored for arrhythmias when the QT interval is prolonged. Persistent QTc measurements exceeding 500 msec will require suspension of asenapine therapy and immediate action to correct any concomitant risk factors before resuming treatment. Particular care should be exercised in patients suspected to be at an increased risk of torsade de pointes. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. In addition, patients should be monitored closely for signs and symptoms of respiratory depression and sedation, and advised to avoid driving or operating hazardous machinery until they know how these medications affect them.
References
Alternative for Tramadol N02A
Naloxone
Ibuprofen
Acetaminophen
Acetylsalicylic acid
Naltrexone
Alternative for Asenapine -

Potential Metabolism Interactions

Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.