The Effects of Co-prescription of Pantoprazole on the Clozapine Metabolism

Kuzin, Maxim; Schoretsanitis, Georgios; Haen, Ekkehard; Dammann, Gerhard; Hiemke, Christoph; Gründer, Gerhard; Paulzen, Michael

doi:10.1055/a-1021-8827

Cited by 5 publications

(9 citation statements)

References 35 publications

(36 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1, List of included studies see Table 1). Twenty-one articles (8,16,(23)(24)(25)(26)(27)(28)(29)(30)(31)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43) investigated differences between smokers and non-smokers as between-subject analyses and two studies (32,33) compared differences as within-subject analyses change of blood levels among smokers after institutional smoking ban). In total, data from 7125 samples were included for the primary outcome (clozapine blood levels in ng/ml) in this meta-analysis.…”

Section: Resultsmentioning

confidence: 99%

“…Of these, 4925 were from smokers and 2185 from non-smokers (N = 21, between-subject analyses) and 15 were smokers and subsequent non-smokers (N = 2, within-subject analyses). 18 out of 23 studies were performed exclusively in schizophrenia-spectrum populations, with the remaining five additionally including (a small amount of) patients with bipolar disorder (26,33), unspecified psychiatric disorders (38,43), and psychiatric disorders except organic disorders (27).…”

Section: Resultsmentioning

confidence: 99%

“…Clozapine blood levels. The 16 studies (8,23,(25)(26)(27)(28)(29)(30)(31)34,35,(37)(38)(39)41,42) reported on blood levels for samples of smokers (n = 4925) and non-smokers (n = 2185). Overall, study quality was moderate, with 6/16 rated as high-quality (23,26,31,35,39,41) and 10 as low/moderate-quality according to modified Newcastle-Ottawa Rating Scale (see Appendix S1).…”

Section: Between-subject Analysesmentioning

confidence: 99%

See 2 more Smart Citations

Impact of smoking behavior on clozapine blood levels – a systematic review and meta‐analysis

Wagner

McMahon

Falkai

et al. 2020

Acta Psychiatr Scand

View full text Add to dashboard Cite

Objective Tobacco smoking significantly impacts clozapine blood levels and has substantial implications on individual efficacy and safety outcomes. By investigating differences in clozapine blood levels in smoking and non‐smoking patients on clozapine, we aim to provide guidance for clinicians how to adjust clozapine levels for patients on clozapine who change their smoking habits. Methods We conducted a meta‐analysis on clozapine blood levels, norclozapine levels, norclozapine/clozapine ratios, and concentration to dose (C/D) ratios in smokers and non‐smokers on clozapine. Data were meta‐analyzed using a random‐effects model with sensitivity analyses on dose, ethnic origin, and study quality. Results Data from 23 studies were included in this meta‐analysis with 21 investigating differences between clozapine blood levels of smokers and non‐smokers. In total, data from 7125 samples were included for the primary outcome (clozapine blood levels in ng/ml) in this meta‐analysis. A meta‐analysis of all between‐subject studies (N = 16) found that clozapine blood levels were significantly lower in smokers compared with non‐smokers (Standard Mean Difference (SMD) −0.39, 95% confidence interval (CI) −0.55 to −0.22, P < 0.001, I2 = 80%). With regard to the secondary outcome, C/D ratios (N = 16 studies) were significantly lower in the smoker group (n = 645) compared with the non‐smoker group (n = 813; SMD −0.70, 95%CI −0.84 to −0.56, P < 0.00001, I2 = 17%). Conclusion Smoking behavior and any change in smoking behavior is associated with a substantial effect on clozapine blood levels. Reductions of clozapine dose of 30% are recommended when a patient on clozapine stops smoking. Reductions should be informed by clozapine steady‐state trough levels and a close clinical risk‐benefit evaluation.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Between-subject Analysesmentioning

confidence: 99%

See 1 more Smart Citation

Impact of smoking behavior on clozapine blood levels – a systematic review and meta‐analysis

Wagner

McMahon

Falkai

et al. 2020

Acta Psychiatr Scand

View full text Add to dashboard Cite

show abstract

“…Unanimously accepted is a strong inducing effect of smoking on cytochrome P450 (CYP) 1A2 isoenzyme activity. Decreased blood levels of CYP1A2 substrates such as clozapine and duloxetine as well as olanzapine are well described [7][8][9][10]; these effects are attributed to the induction of CYP1A2 by polycyclic aromatic hydrocarbons [11]. Case reports of adverse reactions in terms of smoking cessation or changes in smoking habits in clozapine-treated patients highlight the clinical relevance of the smoking effects on drug disposition [12,13].…”

Section: Introductionmentioning

confidence: 99%

Lack of Smoking Effects on Pharmacokinetics of Oral Paliperidone-analysis of a Naturalistic Therapeutic Drug Monitoring Sample

et al. 2020

Self Cite

View full text Add to dashboard Cite

Introduction Major smoking effects have been reported for a series of psychotropic agents, mainly including substrates of CYP450 1A2, although smoking may also affect alternative metabolic pathways. To our knowledge, smoking effects on paliperidone pharmacokinetics have not been assessed yet. Methods We compared plasma concentrations of paliperidone as well as dose-corrected-plasma concentrations (C/D) from a naturalistic database between smokers and nonsmokers using nonparametrical tests, such as the Mann-Whitney U-test (MWU). Additionally, we compared light and heavy smokers with nonsmokers separately. Results Comparing 55 smokers with 37 nonsmokers treated with oral paliperidone, no differences in the percentage of females, age, body weight, body mass index, and daily paliperidone dose were reported (p=0.709 for χ2, p=0.26, p=0.38, p=0.67, and p=0.8 for MWU). No differences were detected in plasma concentrations or C/D values (p=0.50 and p=0.96 for MWU). Likewise, differences in daily dose, plasma concentrations, or C/D values were not significant between light smokers (n=17) and nonsmokers (p=0.61, p=0.81, and p=0.33 for MWU) or heavy smokers (n=22) and nonsmokers (p=0.874, p=0.38, and p=0.59; MWU in all cases). Discussion Paliperidone is not affected by smoking, and paliperidone dose-adjustments in smokers may not be necessary. This may be seen as an essential difference to risperidone, whose cytochrome-mediated metabolism might be affected by smoking.

show abstract

“…Our findings with a lower CLZ concentration and a lower C/D ratio in smokers compared to non-smokers are well known 35,36 and also replicate previous findings. 14,37 In fact, the effect of the smoking on clozapine metabolism is known already more than 30 years. 38 A potential pharmacokinetic interaction between CLZ and a standard therapeutic dose of sertraline considering smoking status is likely to be of minor clinical importance and is consistent with results from older studies.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic interactions between clozapine and sertraline in smokers and non‐smokers

Kuzin

Schoretsanitis

Haen

et al. 2020

Basic Clin Pharma Tox

Self Cite

View full text Add to dashboard Cite

Clozapine is an effective antipsychotic drug for treatment‐resistant schizophrenia. Sertraline is a widely prescribed antidepressant and often concomitantly applied to address negative symptoms or depression. However, data on interactions between clozapine and sertraline are inconsistent. The aim of our study was to evaluate pharmacokinetic interactions between clozapine and sertraline analysing a therapeutic drug monitoring database of 1644 clozapine‐medicated patients. We compared four groups: non‐smokers (n = 250) and smokers (n = 326) with co‐medication without known effects on cytochrome P450 and without sertraline, and non‐smokers (n = 18) and smokers (n = 17) with sertraline co‐medication. Measured and dose‐corrected concentrations (C/D) of clozapine were compared between the groups using non‐parametrical tests with a significance level of 0.05. Post hoc analyses included pairwise comparisons to account for smoking status. Although we detected significant differences for clozapine levels and C/D values between study groups (P < .001 for Kruskal‐Wallis test in both cases), post hoc analyses revealed no differences for concentrations and C/D values of clozapine (P > .05 for Mann‐Whitney U test in both cases). A negative correlation between the sertraline dose and the clozapine concentration was found in non‐smokers (Spearman's rank correlation, rs = −0.535, P = .048). A potential pharmacokinetic interaction between clozapine and a standard therapeutic sertraline dose seems to be of minor clinical importance.

show abstract

The Effects of Co-prescription of Pantoprazole on the Clozapine Metabolism

Cited by 5 publications

References 35 publications

Impact of smoking behavior on clozapine blood levels – a systematic review and meta‐analysis

Impact of smoking behavior on clozapine blood levels – a systematic review and meta‐analysis

Lack of Smoking Effects on Pharmacokinetics of Oral Paliperidone-analysis of a Naturalistic Therapeutic Drug Monitoring Sample

Pharmacokinetic interactions between clozapine and sertraline in smokers and non‐smokers

Contact Info

Product

Resources

About