Clozapine interaction with other drugs

This appears to be an isolated case but it is consistent with the way rifampicin interacts with other drugs. Clozapine serum levels should be well monitored if rifampicin is added, being alert for the need to increase its dosage. An alternative (as in this case) is to use another antibacterial. However, note that there are reports of an interaction between clozapine and ciprofloxacin , (p.749). 

Hypersensitivity to the drug or any other component of the product (cross-sensitivity between phenothiazines may occur) comatose or greatly depressed states caused by CNS depressants or from any other cause (phenothiazines, clozapine, loxapine, molindone, pimozide, haloperidol) coadministration with other drugs that prolong the QT interval and in patients with congenital long QT syndrome or history of cardiac arrhythmias (mesoridazine, thioridazine, pimozide, ziprasidone see Drug..Interactions). 

Pharmacodynamic interactions also occur. In particular, the adverse effects of any drug can be increased by other drugs with similar properties. One example is the reciprocal potentiation of the neurotoxic effects of carbamazepine and lamotrigine in patients taking a combination of these drugs (180). Some drugs (for example ciclosporin, clozapine) have a proconvulsant effect and can reduce the efficacy of antiepileptic drugs. 

Antidepressants are commonly used in combination with antipsychotics to treat depressive symptoms in individuals with schizophrenia. Different antidepressants have been reported to inhibit metabolism of different P450 pathways. Table 66-10 summarizes the potential metabolic drug interactions between antidepressants and SGAs. Potential enzyme inhibitor interactions with clozapine are the most clinically significant. Increased clozapine serum concentrations with a CYP 1A2 inhibitor such as fluvoxamine may precipitate seizures. With the newer atypical antipsychotics, enzyme inhibitors are more likely to cause side effects such as increased sedation, orthostatic hypotension, or increased risk of akathisia and other extrapyramidal side effects. 

V. Drug or laboratory interactions. There is some evidence that milk thistle may inhibit CYP2C9 and CYP3A4 enzyme activity, which might theoretically increase plasma levels of dmgs metabolized by these enzymes, including amitriptyline, diazepam, clozapine, warfarin, mirtazapine, ketoconazole, and others. Drug interactions with milk thistle extract have not been reported in humans. 

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