A Review of the Effect of Vaping on the Plasma Levels of Clozapine and Its Clinical Implications

Nkechinyere Mary Harry *

Vinnytsia National Pirogov Medical University, Vinnytsia Oblast, Ukraine.

Ibrahim L. Folorunsho

Badr Al Janoub Hospital, Najran, Saudi Arabia.

Kenechukwu Anona

University of Ibadan, Ibadan, Nigeria.

Nnenna Okafor

All Saints University, College of Medicine, St Vincent and the Grenadines, Caribbean.

Gibson O. Anugwom

Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas, USA.

*Author to whom correspondence should be addressed.


Background: Clozapine is an antipsychotic medication essential for treating treatment-resistant schizophrenia. Its plasma levels are influenced by cytochrome P450 (CYP450) enzymes, particularly CYP1A2. Vaping and traditional smoking may impact clozapine metabolism.

Objective: This study aims to explore how vaping affects the plasma levels of clozapine, focusing on the pharmacokinetic interactions between clozapine and vaping constituents, and the implications for clinical practice.

Methods: A literature review was conducted to examine the interactions between nicotine smoking, CYP450 enzymes, and clozapine metabolism. Additionally, case reports were analyzed to understand the clinical implications for patients on clozapine who switch from smoking to vaping.

Results: Unlike traditional smoking, vaping lacks combustion products like polycyclic aromatic hydrocarbons (PAHs), leading to reduced CYP1A2 induction. Case reports showed that switching from smoking to vaping often results in elevated plasma clozapine levels due to decreased CYP1A2 activity, causing adverse effects from toxicity. However, some vape products containing combustible products like aldehydes and carbonyls can induce CYP450 enzymes, leading to subtherapeutic plasma clozapine level.

Conclusion: Vaping may affect clozapine metabolism primarily through de-induction of CYP1A2 activity in patients who switch from smoking to vaping. Switching from smoking to vaping can reduce CYP1A2 induction, thereby raising the risk of toxicity due to increased serum clozapine levels. Hence, health professionals should carefully monitor plasma clozapine levels in patients who switch from smoking to vaping and adjust dosages as needed to maintain therapeutic efficacy and minimize adverse effects.

Keywords: Clozapine, vaping, nicotine, smoking, tobacco, cytochrome P450, CYP1A2, schizophrenia

How to Cite

Harry, Nkechinyere Mary, Ibrahim L. Folorunsho, Kenechukwu Anona, Nnenna Okafor, and Gibson O. Anugwom. 2024. “A Review of the Effect of Vaping on the Plasma Levels of Clozapine and Its Clinical Implications”. Journal of Advances in Medicine and Medical Research 36 (7):48-56. https://doi.org/10.9734/jammr/2024/v36i75484.


Download data is not yet available.


Crilly J. The history of clozapine and its emergence in the US market: a review and analysis. Hist Psychiatry. 2007 Mar;18(1): 39–60.

Gammon D, Cheng C, Volkovinskaia A, Baker GB, Dursun SM. Clozapine: why is it so uniquely effective in the treatment of a range of neuropsychiatric disorders? Biomolecules. 2021 Jul 15;11(7).

Müller HHO. Effective and underprescribed: what about clozapine? Ment Illn. 2017 Oct 19;9(2):7193.

Islam F, Hain D, Lewis D, Law R, Brown LC, Tanner J-A, et al. Pharmacogenomics of Clozapine-induced agranulocytosis: A systematic review and meta-analysis. Pharmacogenomics J. 2022 Jul;22(4):230–40.

Mijovic A, MacCabe JH. Clozapine-induced agranulocytosis. Ann Hematol. 2020 Nov;99(11):2477–82.

Idänpään-Heikkilä J, Alhava E, Olkinuora M, Palva IP. Agranulocytosis during treatment with clozapine. Eur J Clin Pharmacol. 1977;11(3):193–8.

Masellis M, Basile VS, Ozdemir V, Meltzer HY, Macciardi FM, Kennedy JL. Pharmacogenetics of antipsychotic treatment: lessons learned from clozapine. Biol Psychiatry. 2000 Feb 1;47(3):252–66.

a. Rao RK, McConnell DD, Litofsky NS. The impact of cigarette smoking and nicotine on traumatic brain injury: a review. Brain injury. 2022 Jan 2;36(1):1-20.

Kluznik JC, Walbek NH, Farnsworth MG, Melstrom K. Clinical effects of a randomized switch of patients from clozaril to generic clozapine. J Clin Psychiatry. 2001;62 Suppl 5:14–7; discussion 23.

Leung JG, Ehret M, Love RC, Cotes RO. Improving clozapine utilization will require continued advocacy, drug sponsor interest, and FDA support to address REMS issues. Expert Rev Clin Pharmacol. 2023 Mar;16(3):177–9.

Thomas AA, Friedman JH. Current use of clozapine in Parkinson disease and related disorders. Clin Neuropharmacol. 2010; 33(1):14–6.

Meltzer HY, Alphs L, Green AI, Altamura AC, Anand R, Bertoldi A, et al. Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Arch Gen Psychiatry. 2003 Jan;60(1):82–91.

Center for Disease Control. About E-Cigarettes (Vapes) | Smoking and Tobacco Use | CDC; 2024 [cited 2024 May 20]. Available:https://www.cdc.gov/tobacco/e-cigarettes/about.html?CDC_AAref_Val=https://www.cdc.gov/tobacco/basic_information/e-cigarettes/about-e-cigarettes.html.

DSHS. What is vaping? Texas DSHS; 2024 [cited 2024 May 23]. Available:https://www.dshs.texas.gov/vaping/what-is-vaping.

American Heart Association. Is Vaping Better Than Smoking? | American Heart Association [Internet]. [cited 2024 May 23]. Available:https://www.heart.org/en/healthy-living/healthy-lifestyle/quit-smoking-tobacco/is-vaping-safer-than-smoking.

HopkinsMedicine.org. Vape Flavors and Vape Juice: What You Need to Know | Johns Hopkins Medicine. [cited 2024 May 23]. Available:https://www.hopkinsmedicine.org/health/wellness-and-prevention/vape-flavors-and-vape-juice-what-you-need-to-know#:~:text=But%20there%20are%20unknowns%20%E2%80%94%20research,more%20than%20just%20the%20lungs.

Ding JB, Hu K. Cigarette smoking and schizophrenia: etiology, clinical, pharmacological, and treatment implications. Schizophr Res Treatment. 2021 Dec 13;2021:7698030.

Miller BJ, Wang A, Wong J, Paletta N, Buckley PF. Electronic cigarette use in patients with schizophrenia: Prevalence and attitudes. Ann Clin Psychiatry. 2017 Feb;29(1):4–10.

Prior TI, Chue PS, Tibbo P, Baker GB. Drug metabolism and atypical antipsychotics. Eur Neuropsychopharmacol. 1999 Jun;9(4): 301–9.

Pirmohamed M, Williams D, Madden S, Templeton E, Park BK. Metabolism and bioactivation of clozapine by human liver in vitro. J Pharmacol Exp Ther. 1995 Mar; 272(3):984–90.

Spina E, Avenoso A, Facciolà G, Scordo MG, Ancione M, Madia AG, et al. Relationship between plasma concentrations of clozapine and norclozapine and therapeutic response in patients with schizophrenia resistant to conventional neuroleptics. Psychopharmacology. 2000 Jan;148(1): 83–9.

Haslemo T, Eikeseth PH, Tanum L, Molden E, Refsum H. The effect of variable cigarette consumption on the interaction with clozapine and olanzapine. Eur J Clin Pharmacol. 2006 Dec;62(12): 1049–53.

Dean L. Clozapine therapy and CYP2D6, CYP1A2, and CYP3A4 genotypes. In: Pratt V, McLeod H, Dean L, Malheiro A, Rubinstein W, editors. Medical Genetics Summaries. Bethesda (MD): National Center for Biotechnology Information (US); 2012.

Blacker CJ. Clinical issues to consider for clozapine patients who vape: A case illustration. Focus (Am Psychiatr Publ). 2020 Jan 24;18(1):55–7.

Thorn CF, Müller DJ, Altman RB, Klein TE. PharmGKB summary: clozapine pathway, pharmacokinetics. Pharmacogenet Genomics. 2018;28(9):214–22.

Kocar T, Freudenmann RW, Spitzer M, Graf H. Switching from tobacco smoking to electronic cigarettes and the impact on clozapine levels. J Clin Psychopharmacol. 2018 Oct;38(5):528–9.

Costa-Dookhan KA, Agarwal SM, Chintoh A, Tran VN, Stogios N, Ebdrup BH, et al. The clozapine to norclozapine ratio: a narrative review of the clinical utility to minimize metabolic risk and enhance clozapine efficacy. Expert Opin Drug Saf. 2020 Jan;19(1):43–57.

psychopharmacologyinstitute.com. Psychopharmacology Institute [Internet]. [cited 2024 May Available:https://psychopharmacologyinstitute.com/section/managing-clozapine-related-sialorrhea-2688-5329

Conklin DJ, Ogunwale MA, Chen Y, Theis WS, Nantz MH, Fu X-A, et al. Electronic cigarette-generated aldehydes: The contribution of e-liquid components to their formation and the use of urinary aldehyde metabolites as biomarkers of exposure. Aerosol Sci Technol. 2018 Aug 23;52(11): 1219–32.

Ogunwale MA, Li M, Ramakrishnam Raju MV, Chen Y, Nantz MH, Conklin DJ, et al. Aldehyde detection in electronic cigarette aerosols. ACS Omega. 2017 Mar 31;2(3):1207–14.

Winters BR, Kochar TK, Clapp PW, Jaspers I, Madden MC. Impact of E-Cigarette Liquid Flavoring Agents on Activity of Microsomal Recombinant CYP2A6, the Primary Nicotine-Metabolizing Enzyme. Chem Res Toxicol. 2020 Jul 20;33(7):1689–97.

Li Y, Meng Q, Yang M, Liu D, Hou X, Tang L, et al. Current trends in drug metabolism and pharmacokinetics. Acta Pharm Sin B. 2019 Nov;9(6):1113–44.

Khorassani F, Kaufman M, Lopez LV. Supatherapeutic serum clozapine concentration after transition from traditional to electronic cigarettes. J Clin Psychopharmacol. 2018 Aug;38(4): 391–2.

Snyder M, Smith T. Case Report: The clinical implications of clozapine and cigarette smoking. Mental Health Clinician. 2011 Nov;1(5):107–9.

Mayerova M, Ustohal L, Jarkovsky J, Pivnicka J, Kasparek T, Ceskova E. Influence of dose, gender, and cigarette smoking on clozapine plasma concentrations. Neuropsychiatr Dis Treat. 2018 Jun 14;14:1535–43.

Montville DJ, Lindsey JM, Leung JG. Fluctuation between cigarette smoking and use of electronic nicotine delivery systems: Impact on clozapine concentrations and clinical effect. Ment Health Clin. 2021 Nov 8;11(6):365–8.

Tamargo J, Le Heuzey JY, Mabo P. Narrow therapeutic index drugs:A clinical pharmacological consideration to flecainide. Eur J Clin Pharmacol. 2015 May;71(5):549–67.