Interaction between Clozapine and Mirtazapine
Major Synergy

ID DDInter419 and DDInter1230
Interaction Coadministration with other psychotropic agents may potentiate the adverse effects of clozapine on cardiovascular function. Orthostatic hypotension with or without syncope, in rare cases accompanied by profound collapse and cardiorespiratory arrest, has occurred during initiation of clozapine treatment alone and in combination with other psychotropic agents, occasionally even on the first dose.
acute pancreatitis adrenal insufficiency alcohol consumption aneurysm aphasia Aching joints Ataxia biliary tract disorder choking colostomy More
Management Caution is advised when clozapine is initiated in patients receiving other psychotropic drugs. Vital signs should be closely monitored. Patients who have had even a brief interval off clozapine (i.e. 2 or more days since the last dose) should be restarted with 12.5 mg once or twice daily. The potential for additive effects on the QT interval and increased risk of torsade de pointes arrhythmia should also be considered when clozapine is used in combination with phenothiazines, tricyclic antidepressants, some atypical antipsychotics (e.g., asenapine, quetiapine, iloperidone, iloperidone, paliperidone, risperidone, ziprasidone), or other psychotherapeutic agents that can prolong the QT interval such as amoxapine, haloperidol, maprotiline, mirtazapine, and trazodone. Serum electrolytes, including potassium, magnesium and calcium, should be measured at baseline and periodically during treatment, and any abnormalities corrected prior to initiating clozapine. Routine ECG assessment may detect QTc prolongation but is not always effective in preventing arrhythmias. Clozapine treatment should be discontinued if the QTc interval exceeds 500 msec. 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.
References
Alternative for Clozapine -
Alternative for Mirtazapine N06A

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.