{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T01:58:29Z","timestamp":1792979909507,"version":"4.5.0"},"reference-count":27,"publisher":"American Association of Psychiatric Pharmacists (AAPP)","issue":"3","license":[{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"},{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n        <jats:p>Clozapine is primarily metabolized via cytochrome P450(CYP)1A2 and to a lesser extent CYP3A4, CYP2C19, and CYP2D6. Metabolic inhibitors of clozapine, such as fluvoxamine and ciprofloxacin, are important to recognize to avoid adverse drug events. Estrogen-containing oral contraceptives (eOCPs) are weaker CYP1A2 and CYP2C19 inhibitors but are associated with a 2-fold increase of clozapine concentrations. The potential for phenoconversion due to a CYP genetic polymorphism can add additional complexities when considering drug interactions. A case report is presented of a suspected interaction between newly initiated clozapine and a prescribed eOCP for which the patient\u2019s pharmacogenomic status was known. A 17-year-old, nonsmoking, White female with a history of schizophrenia was initiated on clozapine 12.5 mg at bedtime with a plan to increase by 25 mg every 4 days in the outpatient setting. The patient was a known rapid CYP1A2 metabolizer without identified sources of CYP1A2 induction and a CYP2C19 rapid metabolizer. Based on pharmacogenomic testing, there was no suspicion for significant gene-drug interactions. Yet, as the patient was prescribed an eOCP, a clozapine concentration was obtained after reaching 150 mg at bedtime. This steady-state clozapine concentration was found to be 560 ng\/mL, correlating with worsening sedation and constipation. Given ongoing side effects, clozapine was lowered to 100 mg at bedtime; however, ongoing intolerance ultimately led to clozapine discontinuation. This case highlights the potential interaction between clozapine and eOCP in a CYP1A2 and CYP2C19 rapid metabolizer, leading to clozapine intolerance and discontinuation. The concomitant use of clozapine and eOCPs should be undertaken judiciously.<\/jats:p>","DOI":"10.9740\/mhc.2024.06.220","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T00:02:05Z","timestamp":1717372925000},"page":"220-223","source":"Crossref","is-referenced-by-count":6,"title":["The potential influence of estrogen-containing oral contraception on clozapine metabolism in a patient with known pharmacogenomic status"],"prefix":"10.9740","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3875-9199","authenticated-orcid":true,"given":"Alyssa K.","family":"Kuhn","sequence":"first","affiliation":[{"name":"Pharmacy Student, University of Wisconsin-Madison School of Pharmacy, Madison, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0479-9462","authenticated-orcid":true,"given":"Meina L.","family":"Determan","sequence":"additional","affiliation":[{"name":"Pharmacy Student, Texas A&M University School of Pharmacy, Kingsville, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9659-4875","authenticated-orcid":true,"given":"Jessica A.","family":"Wright","sequence":"additional","affiliation":[{"name":"Pharmacist, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9436-8137","authenticated-orcid":true,"given":"Eric","family":"Matey","sequence":"additional","affiliation":[{"name":"Pharmacist, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3836-9375","authenticated-orcid":true,"given":"Jonathan G.","family":"Leung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4719","reference":[{"key":"i2168-9709-14-3-220-b01","author":"DailyMed-CLOZAPINE tablet","unstructured":"DailyMed-CLOZAPINE tablet\n          . 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DOI: 10.1176\/appi.psy.48.2.170"},{"issue":"4","key":"i2168-9709-14-3-220-b17","series-title":"Eur J Clin Pharmacol","first-page":"343","article-title":"Determination of -3858G\u2013>A and -164C\u2013>A genetic polymorphisms of CYP1A2 in blood and saliva by rapid allelic discrimination: large difference in the prevalence of the -3858G\u2013>A mutation between Caucasians and Asians","volume":"59","author":"Todesco","year":"2003","unstructured":"Todesco\n              L,\n            \n            \n              T\u00f6r\u00f6k\n              M,\n            \n            \n              Kr\u00e4henb\u00fchl\n              S,\n            \n            \n              Wenk\n              M.\n            \n          \n          Determination of -3858G\u2013>A and -164C\u2013>A genetic polymorphisms of CYP1A2 in blood and saliva by rapid allelic discrimination: large difference in the prevalence of the -3858G\u2013>A mutation between Caucasians and Asians. Eur J Clin Pharmacol. 2003;59(4):343-6. DOI: 10.1007\/s00228-003-0623-1"},{"issue":"12","key":"i2168-9709-14-3-220-b18","series-title":"Eur J Clin Pharmacol","first-page":"887","article-title":"Rapid genotyping for relevant CYP1A2 alleles by pyrosequencing","volume":"61","author":"Skarke","year":"2005","unstructured":"Skarke\n              C,\n            \n            \n              Kirchhof\n              A,\n            \n            \n              Geisslinger\n              G,\n            \n            \n              L\u00f6tsch\n              J.\n            \n          \n          Rapid genotyping for relevant CYP1A2 alleles by pyrosequencing. Eur J Clin Pharmacol. 2005;61(12):887-92. DOI: 10.1007\/s00228-005-0029-3"},{"issue":"1","key":"i2168-9709-14-3-220-b19","series-title":"Pharmacogenomics J","first-page":"60","article-title":"Genetic susceptibility to tardive dyskinesia in chronic schizophrenia subjects: i. association of CYP1A2 gene polymorphism","volume":"5","author":"Tiwari","year":"2005","unstructured":"Tiwari\n              AK,\n            \n            \n              Deshpande\n              SN,\n            \n            \n              Rao\n              AR,\n            \n            et al.\n          \n          Genetic susceptibility to tardive dyskinesia in chronic schizophrenia subjects: i. association of CYP1A2 gene polymorphism. Pharmacogenomics J. 2005;5(1):60-9. DOI: 10.1038\/sj.tpj.6500282"},{"issue":"2","key":"i2168-9709-14-3-220-b20","series-title":"Pharmacogenomics J","first-page":"192","article-title":"Impact of CYP1A2, CYP2C19, and CYP2D6 genotype- and phenoconversion-predicted enzyme activity on clozapine exposure and symptom severity","volume":"20","author":"Lesche","year":"2020","unstructured":"Lesche\n              D,\n            \n            \n              Mostafa\n              S,\n            \n            \n              Everall\n              I,\n            \n            \n              Pantelis\n              C,\n            \n            \n              Bousman\n              CA.\n            \n          \n          Impact of CYP1A2, CYP2C19, and CYP2D6 genotype- and phenoconversion-predicted enzyme activity on clozapine exposure and symptom severity. Pharmacogenomics J. 2020;20(2):192-201. 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DOI: 10.1080\/15622975.2017.1347712"},{"key":"i2168-9709-14-3-220-b22","series-title":"Asian J Psychiatry","first-page":"102126","article-title":"Unusually high serum levels of clozapine associated with genetic polymorphism of CYP3A enzymes","volume":"57","author":"John","year":"2021","unstructured":"John\n              AP,\n            \n            \n              Kecanovic\n              A.\n            \n          \n          Unusually high serum levels of clozapine associated with genetic polymorphism of CYP3A enzymes. Asian J Psychiatry. 2021;57:102126. DOI: 10.1016\/j.ajp.2020.102126"},{"issue":"7","key":"i2168-9709-14-3-220-b23","series-title":"Int J Neuropsychopharmacol","first-page":"529","article-title":"Potential role of patients\u2019 CYP3A-status in clozapine pharmacokinetics","volume":"20","author":"T\u00f3th","year":"2017","unstructured":"T\u00f3th\n              K,\n            \n            \n              Csukly\n              G,\n            \n            \n              Sirok\n              D,\n            \n            et al.\n          \n          Potential role of patients\u2019 CYP3A-status in clozapine pharmacokinetics. Int J Neuropsychopharmacol. 2017;20(7):529-37. DOI: 10.1093\/ijnp\/pyx019"},{"issue":"1","key":"i2168-9709-14-3-220-b24","series-title":"Sci Rep","first-page":"21283","article-title":"Association of clozapine-related metabolic disturbances with CYP3A4 expression in patients with schizophrenia","volume":"10","author":"Menus","year":"2020","unstructured":"Menus\n              \u00c1,\n            \n            \n              Kiss\n              \u00c1,\n            \n            \n              T\u00f3th\n              K,\n            \n            et al.\n          \n          Association of clozapine-related metabolic disturbances with CYP3A4 expression in patients with schizophrenia. Sci Rep. 2020;10(1):21283. DOI: 10.1038\/s41598-020-78474-0"},{"issue":"1","key":"i2168-9709-14-3-220-b25","series-title":"Indian J Psychol Med","first-page":"4","article-title":"Do Asian patients require only half of the clozapine dose prescribed for Caucasians? A critical overview","volume":"42","author":"de Leon","year":"2020","unstructured":"de Leon\n              J,\n            \n            \n              Rajkumar\n              AP,\n            \n            \n              Kaithi\n              AR,\n            \n            et al.\n          \n          Do Asian patients require only half of the clozapine dose prescribed for Caucasians? A critical overview. Indian J Psychol Med. 2020;42(1):4-10. DOI: 10.4103\/IJPSYM.IJPSYM_379_19"},{"issue":"1","key":"i2168-9709-14-3-220-b26","series-title":"Transl Psychiatry","first-page":"198","article-title":"Identification of a novel polymorphism associated with reduced clozapine concentration in schizophrenia patients\u2014a genome-wide association study adjusting for smoking habits","volume":"10","author":"Smith","year":"2020","unstructured":"Smith\n              RL,\n            \n            \n              O\u2019Connell\n              K,\n            \n            \n              Athanasiu\n              L,\n            \n            et al.\n          \n          Identification of a novel polymorphism associated with reduced clozapine concentration in schizophrenia patients\u2014a genome-wide association study adjusting for smoking habits. Transl Psychiatry. 2020;10(1):198. DOI: 10.1038\/s41398-020-00888-1"},{"issue":"1","key":"i2168-9709-14-3-220-b27","series-title":"Acta Psychiatr Scand","first-page":"15","article-title":"Augmentation of clozapine with a second antipsychotic\u2014a meta-analysis","volume":"125","author":"Taylor","year":"2012","unstructured":"Taylor\n              DM,\n            \n            \n              Smith\n              L,\n            \n            \n              Gee\n              SH,\n            \n            \n              Nielsen\n              J.\n            \n          \n          Augmentation of clozapine with a second antipsychotic\u2014a meta-analysis. Acta Psychiatr Scand. 2012;125(1):15-24. 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