Editing Clozapine (section)

== Drug interactions ==
[[Fluvoxamine]] inhibits the metabolism of clozapine leading to significantly increased blood levels of clozapine.<ref>{{cite journal | vauthors = Sproule BA, Naranjo CA, Brenmer KE, Hassan PC | title = Selective serotonin reuptake inhibitors and CNS drug interactions. A critical review of the evidence | journal = Clinical Pharmacokinetics | volume = 33 | issue = 6 | pages = 454–471 | date = December 1997 | pmid = 9435993 | doi = 10.2165/00003088-199733060-00004 | s2cid = 36883635 }}</ref>

When [[carbamazepine]] is concurrently used with clozapine, it has been shown to decrease plasma levels of clozapine significantly thereby decreasing the beneficial effects of clozapine.<ref>{{cite journal | vauthors = Tiihonen J, Vartiainen H, Hakola P | title = Carbamazepine-induced changes in plasma levels of neuroleptics | journal = Pharmacopsychiatry | volume = 28 | issue = 1 | pages = 26–28 | date = January 1995 | pmid = 7746842 | doi = 10.1055/s-2007-979584 | s2cid = 260249900 }}</ref><ref>{{cite journal | vauthors = Besag FM, Berry D | title = Interactions between antiepileptic and antipsychotic drugs | journal = Drug Safety | volume = 29 | issue = 2 | pages = 95–118 | year = 2006 | pmid = 16454538 | doi = 10.2165/00002018-200629020-00001 | s2cid = 45735414 }}</ref> Patients should be monitored for "decreased therapeutic effects of clozapine if carbamazepine" is started or increased. If carbamazepine is discontinued or the dose of [[carbamazepine]] is decreased, therapeutic effects of clozapine should be monitored. The study recommends [[carbamazepine]] to not be used concurrently with clozapine due to increased risk of [[agranulocytosis]].<ref>{{cite journal | vauthors = Jerling M, Lindström L, Bondesson U, Bertilsson L | title = Fluvoxamine inhibition and carbamazepine induction of the metabolism of clozapine: evidence from a therapeutic drug monitoring service | journal = Therapeutic Drug Monitoring | volume = 16 | issue = 4 | pages = 368–374 | date = August 1994 | pmid = 7974626 | doi = 10.1097/00007691-199408000-00006 | s2cid = 31325882 }}</ref>

[[Ciprofloxacin]] is an inhibitor of [[CYP1A2]] and clozapine is a major CYP1A2 substrate. Randomized study reported elevation in clozapine concentration in subjects concurrently taking [[ciprofloxacin]].<ref>{{cite journal | vauthors = Raaska K, Neuvonen PJ | title = Ciprofloxacin increases serum clozapine and N-desmethylclozapine: a study in patients with schizophrenia | journal = European Journal of Clinical Pharmacology | volume = 56 | issue = 8 | pages = 585–589 | date = November 2000 | pmid = 11151749 | doi = 10.1007/s002280000192 | s2cid = 20390680 }}</ref> Thus, the prescribing information for clozapine recommends "reducing the dose of clozapine by one-third of original dose" when [[ciprofloxacin]] and other [[CYP1A2]] inhibitors are added to therapy, but once [[ciprofloxacin]] is removed from therapy, it is recommended to return clozapine to original dose.<ref>Prescribing information. Clozaril (clozapine). East Hanover, NJ: Novartis Pharmaceuticals Corporation, September 2014.</ref>

[[Smoking]] induces [[CYP1A2]] enzyme activity, which accelerates the metabolism of clozapine and reduces its plasma concentrations. Smoking on average reduced the concentration by 30%, but some people may see as much as a 50% reduction.<ref>{{cite journal | vauthors = Wagner E, McMahon L, Falkai P, Hasan A, Siskind D | title = Impact of smoking behavior on clozapine blood levels - a systematic review and meta-analysis | journal = Acta Psychiatrica Scandinavica | volume = 142 | issue = 6 | pages = 456–466 | date = December 2020 | pmid = 32869278 | doi = 10.1111/acps.13228 | doi-access = free }}</ref>

The FDA warns that caution should be used when combining clozapine with drugs that depress the [[central nervous system]] ([[Alcohol (drug)|alcohol]], [[Benzodiazepine|benzodiazepines]], and [[Opioid|opioids)]]<ref name=":0">{{Cite web |last=Pharmaceuticals Corporation |first=Novartis |date=26 September 1989 |title=Norartis |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019758s062lbl.pdf |website=FDA}}</ref><ref>{{cite journal | vauthors = Faisal I, lindenmayer JP, Taintor Z, Cancro R | title = Clozapine-benzodiazepine interactions | journal = The Journal of Clinical Psychiatry | volume = 58 | issue = 12 | pages = 547–548 | date = December 1997 | pmid = 9448658 | doi = 10.4088/JCP.v58n1206a }}</ref> As using these drugs together can lead to a potentially life threatening complication known as [[Hypoventilation|Respiratory depression]].