Summary of Product Characteristic for Clozaril 25 mg Tablets. Updated on the emc: 12-May-2020 [Internet]. https://www.medicines.org.uk/emc/product/4411/smpc. Accessed Oct 2022

Sagud M (2015) Treatment-resistant schizophrenia: challenges and implications for clinical practice. Psychiat Danub 27(3):319–326

Google Scholar 

Mauri MC, Paletta S, Di Pace C, Reggiori A, Cirnigliaro G, Valli I, Altamura AC (2018) Clinical pharmacokinetics of atypical antipsychotics: an update. Clin Pharmacokinet 57(12):1493–1528. https://doi.org/10.1007/s40262-018-0664-3

Article  CAS  PubMed  Google Scholar 

Olmos I, Ibarra M, Vazquez M, Maldonado C, Fagiolino P, Giachetto G (2019) Population pharmacokinetics of clozapine and norclozapine and switchability assessment between brands in Uruguayan patients with schizophrenia. Biomed Res Int 2019:3163502. https://doi.org/10.1155/2019/3163502

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nielsen J, Damkier P, Lublin H, Taylor D (2011) Optimizing clozapine treatment. Acta Psychiatr Scand 123(6):411–422. https://doi.org/10.1111/j.1600-0447.2011.01710.x

Article  CAS  PubMed  Google Scholar 

Hiemke C, Bergemann N, Clement HW et al (2018) Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: update 2017. Pharmacopsychiatry 51(1–02):e1. https://doi.org/10.1055/s-0037-1600991

Article  CAS  PubMed  Google Scholar 

Grundmann M, Kacirova I, Urinovska R (2014) Therapeutic drug monitoring of atypical antipsychotic drugs. Acta Pharm 64(4):387–401. https://doi.org/10.2478/acph-2014-0036

Article  CAS  PubMed  Google Scholar 

Sheehan JJ, Sliwa JK, Amatniek JC, Grinspan A, Canuso CM (2010) Atypical antipsychotic metabolism and excretion. Curr Drug Metab 11(6):516–525

Article  CAS  PubMed  Google Scholar 

Mauri MC, Volonteri LS, Colasanti A, Fiorentini A, De Gaspari IF, Bareggi SR (2007) Clinical pharmacokinetics of atypical antipsychotics: a critical review of the relationship between plasma concentrations and clinical response. Clin Pharmacokinet 46(5):359–388. https://doi.org/10.2165/00003088-200746050-00001

Article  CAS  PubMed  Google Scholar 

Krivoy A, Gaughran F, Weizman A, Breen G, MacCabe JH (2016) Gene polymorphisms potentially related to the pharmacokinetics of clozapine: a systematic review. Int Clin Psychopharmacol 31(4):179–184. https://doi.org/10.1097/YIC.0000000000000065

Article  PubMed  Google Scholar 

Stark A, Scott J (2012) A review of the use of clozapine levels to guide treatment and determine cause of death. Aust N Z J Psychiatry 46(9):816–825. https://doi.org/10.1177/0004867412438871

Article  PubMed  Google Scholar 

Hommers L, Scharl M, Hefner G, Hohner M, Fischer M, Pfuhlmann B, Deckert J, Unterecker S (2018) Comedication of valproic acid is associated with increased metabolism of clozapine. J Clin Psychopharmacol 38(3):188–192. https://doi.org/10.1097/JCP.0000000000000877

Article  CAS  PubMed  Google Scholar 

Tang YL, Mao P, Li FM, Li W, Chen Q, Jiang F, Cai ZJ, Mitchell PB (2007) Gender, age, smoking behaviour and plasma clozapine concentrations in 193 Chinese inpatients with schizophrenia. Br J Clin Pharmacol 64(1):49–56. https://doi.org/10.1111/j.1365-2125.2007.02852.x

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mayerova M, Ustohal L, Jarkovsky J, Pivnicka J, Kasparek T, Ceskova E (2018) Influence of dose, gender, and cigarette smoking on clozapine plasma concentrations. Neuropsychiatr Dis Treat 14:1535–1543. https://doi.org/10.2147/NDT.S163839

Article  CAS  PubMed  PubMed Central  Google Scholar 

Marazziti D, Palego L, Betti L, Giannaccini G, Massimetti E, Baroni S, Ciapparelli A, Lucacchini A, Mucci F, Dell’Osso L (2018) Effect of valproate and antidepressant drugs on clozapine metabolism in patients with psychotic mood disorders. Ther Drug Monit 40(4):443–451. https://doi.org/10.1097/FTD.0000000000000513

Article  CAS  PubMed  Google Scholar 

Rajkumar AP, Poonkuzhali B, Kuruvilla A, Jacob M, Jacob KS (2013) Clinical predictors of serum clozapine levels in patients with treatment-resistant schizophrenia. Int Clin Psychopharmacol 28(1):50–56. https://doi.org/10.1097/YIC.0b013e32835ac9da

Article  PubMed  Google Scholar 

Palego L, Biondi L, Giannaccini G, Sarno N, Elmi S, Ciapparelli A, Cassano GB, Lucacchini A, Martini C, Dell’Osso L (2002) Clozapine, norclozapine plasma levels, their sum and ratio in 50 psychotic patients: influence of patient-related variables. Prog Neuropsychopharmacol Biol Psychiatry 26(3):473–480. https://doi.org/10.1016/s0278-5846(01)00291-3

Article  CAS  PubMed  Google Scholar 

Jovanovic M, Vucicevic K, Miljkovic B (2020) Understanding variability in the pharmacokinetics of atypical antipsychotics - focus on clozapine, olanzapine and aripiprazole population models. Drug Metab Rev 52(1):1–18. https://doi.org/10.1080/03602532.2020.1717517

Article  CAS  PubMed  Google Scholar 

Rostami-Hodjegan A, Amin AM, Spencer EP, Lennard MS, Tucker GT, Flanagan RJ (2004) Influence of dose, cigarette smoking, age, sex, and metabolic activity on plasma clozapine concentrations: a predictive model and nomograms to aid clozapine dose adjustment and to assess compliance in individual patients. J Clin Psychopharmacol 24(1):70–78. https://doi.org/10.1097/01.jcp.0000106221.36344.4d

Article  CAS  PubMed  Google Scholar 

Hefner G, Shams ME, Unterecker S, Falter T, Hiemke C (2016) Inflammation and psychotropic drugs: the relationship between C-reactive protein and antipsychotic drug levels. Psychopharmacology 233(9):1695–1705. https://doi.org/10.1007/s00213-015-3976-0

Article  CAS  PubMed  Google Scholar 

Castberg I, Westin AA, Skogvoll E, Spigset O (2017) Effects of age and gender on the serum levels of clozapine, olanzapine, risperidone, and quetiapine. Acta Psychiatr Scand 136(5):455–464. https://doi.org/10.1111/acps.12794

Article  CAS  PubMed  Google Scholar 

Lane HY, Chang YC, Chang WH, Lin SK, Tseng YT, Jann MW (1999) Effects of gender and age on plasma levels of clozapine and its metabolites: analyzed by critical statistics. J Clin Psychiatry 60(1):36–40. https://doi.org/10.4088/jcp.v60n0108

Article  CAS  PubMed  Google Scholar 

Diaz FJ, Santoro V, Spina E, Cogollo M, Rivera TE, Botts S, de Leon J (2008) Estimating the size of the effects of co-medications on plasma clozapine concentrations using a model that controls for clozapine doses and confounding variables. Pharmacopsychiatry 41(3):81–91. https://doi.org/10.1055/s-2007-1004591

Article  CAS  PubMed  Google Scholar 

Tsuda Y, Saruwatari J, Yasui-Furukori N (2014) Meta-analysis: the effects of smoking on the disposition of two commonly used antipsychotic agents, olanzapine and clozapine. BMJ Open 4(3):e004216. https://doi.org/10.1136/bmjopen-2013-004216

Article  PubMed  PubMed Central  Google Scholar 

Ng W, Uchida H, Ismail Z, Mamo DC, Rajji TK, Remington G, Sproule B, Pollock BG, Mulsant BH, Bies RR (2009) Clozapine exposure and the impact of smoking and gender: a population pharmacokinetic study. Ther Drug Monit 31(3):360–366. https://doi.org/10.1097/FTD.0b013e31819c7037

Article  CAS  PubMed  Google Scholar 

Longo LP, Salzman C (1995) Valproic acid effects on serum concentrations of clozapine and norclozapine. Am J Psychiatry 152(4):650. https://doi.org/10.1176/ajp.152.4.650a

Article  CAS  PubMed  Google Scholar 

Smith RL, Kylleso L, Haslemo T, Andreassen OA, Molden E (2019) Reduction in N-desmethylclozapine level is determined by daily dose but not serum concentration of valproic acid-indications of a presystemic interaction mechanism. Ther Drug Monit 41(4):503–508. https://doi.org/10.1097/FTD.0000000000000619

Article  CAS  PubMed  Google Scholar 

Smith RL, Wollmann BM, Kylleso L, Tran TTA, Tveito M, Molden E (2022) Effect of valproic acid on the metabolic spectrum of clozapine in patients with schizophrenia. J Clin Psychopharmacol 42(1):43–50. https://doi.org/10.1097/JCP.0000000000001507

Article  CAS  PubMed  Google Scholar 

Moffat AC, Osselton MD, Widdop B (ed) (2011) Clark's analysis of drugs and poisons, 4th edn. Pharmaceutical Press

Epocrates Interaction Check [Internet]. https://online.epocrates.com/interaction-check. Accessed Dec 2022

Couchman L, Morgan PE, Spencer EP, Flanagan RJ (2010) Plasma clozapine, norclozapine, and the clozapine:norclozapine ratio in relation to prescribed dose and other factors: data from a therapeutic drug monitoring service, 1993–2007. Ther Drug Monit 32(4):438–447. https://doi.org/10.1097/FTD.0b013e3181dad1fb

Article  CAS  PubMed  Google Scholar 

Wohkittel C, Gerlach M, Taurines R, Wewetzer C, Unterecker S, Burger R, Schreck D, Mehler-Wex C, Romanos M, Egberts K (2016) Relationship between clozapine dose, serum concentration, and clinical outcome in children and adolescents in clinical practice. J Neural Transm 123(8):1021–1031. https://doi.org/10.1007/s00702-016-1573-y

Article  CAS  PubMed  Google Scholar 

Corrigendum (2019) Erratum: Influence of dose, gender, and cigarette smoking on clozapine plasma concentrations [Corrigendum]. Neuropsychiatr Dis Treat 15:655. https://doi.org/10.2147/NDT.S205205

Article  Google Scholar 

Ellison JC, Dufresne RL (2015) A review of the clinical utility of serum clozapine and norclozapine levels. Mental Health Clin 5(2):68–73

Article  Google Scholar 

Remington G, Agid O, Foussias G, Ferguson L, McDonald K, Powell V (2013) Clozapine and therapeutic drug monitoring: is there sufficient evidence for an upper threshold? Psychopharmacology 225(3):505–518. https://doi.org/10.1007/s00213-012-2922-7

Article  CAS