The cytochrome P450 isoenzyme 1A2 is primarily responsible for clozapine metabolism, but 2C, 2D6, 2E1 and 3A3/4 appear to play roles as well. Agents that induce (e.g., cigarette smoke) or inhibit (e.g., theophylline, ciprofloxacin, fluvoxamine) CYP1A2 may increase or decrease, respectively, the metabolism of clozapine. For example, the induction of metabolism caused by smoking means that smokers require up to double the dose of clozapine compared with non-smokers to achieve an equivalent plasma concentration.Clozapine and norclozapine (desmethyl-clozapine) plasma levels may also be monitored, though they show a significant degree of variation and are higher in women and increase with age. Monitoring of plasma levels of clozapine and norclozapine has been shown to be useful in assessment of compliance, metabolic status, prevention of toxicity, and in dose optimisation. Society and culture
Economics
Despite the expense of the risk monitoring and management systems required, clozapine use is highly cost effective; with a number of studies suggesting savings of tens of thousands of dollars per patient per year compared to other antipsychotics as well as advantages regarding improvements in quality of life. Clozapine is available as a generic medication. Clozapine in the arts
Carrie Mathison, a fictional CIA operative in the television series Homeland secretly takes clozapine supplied by her sister for the treatment of bipolar disorder. In the film Out of Darkness, Diana Ross played the protagonist Paulie Cooper, "a paranoid schizophrenic" who is depicted as having a dramatic improvement on clozapine.
Despite the risk for numerous side effects, many side effects can be managed while continuing to take clozapine. Neutropenia and agranulocytosis
Clozapine Induced Neutropenia (CIN) occurs in approximately 3.8% of cases and Clozapine Induced Agranulocytosis (CIA) in 0.4%. These are potentially serious side effects and agranulocytosis can result in death. To mitigate this risk clozapine is only used with mandatory  absolute neutrophil count (ANC) monitoring (neutrophils are the most abundant of the granulocytes); for example, in the United States, the Risk Evaluation and Mitigation Strategy (REMS). The exact schedules and blood count thresholds vary internationally and the thresholds at which clozapine can be used in the U.S. has been lower than those currently used in the U.K. and Australasia for some time. The effectiveness of the risk management strategies used is such that deaths from these side effects are very rare occurring at approximately 1 in 7700 patients treated. Almost all the adverse blood reactions occur within the first year of treatment and the majority within the first 18 weeks. After one year of treatment these risks reduce markedly to that seen in other antipsychotic drugs 0.01% or about 1 in 10,000 and the risk of death is markedly lower still. When reductions in neutrophil levels are noted on regular blood monitoring then, depending on the value, monitoring may be increased or, if the neutrophil count is sufficiently low, then clozapine is stopped immediately and can then no longer be used within the medicinal licence. Stopping clozapine almost always results in resolution of the neutrophil reduction.