clozapine and Eosinophilia

Drug-induced pleural disease is uncommon and less known to clinicians than drug-induced parenchymal lung disease. Pleural reactions from drugs manifest as pleural effusions, pleural thickening, or pleuritic chest pain, and may occur in the absence of parenchymal infiltrates. The clinician should be cognizant of the possibility of a drug-induced pleural reaction. A detailed drug history, temporal relationship between symptom onset and initiation of therapy, and pleural fluid eosinophilia should raise the suspicion of a drug-related process. We suspect that as new drugs are marketed in the United States, the number of drugs that result in pleuropulmonary toxicity will continue to increase. Moreover, if the cause of an exudative pleural effusion is not clinically obvious after pleural fluid analysis, drug therapy withdrawal should be a consideration if clinically appropriate before initiating an extensive diagnostic evaluation that may entail unnecessary economic burden and discomfort for the patient.

Topics: Anti-Infective Agents, Urinary; Antimetabolites, Antineoplastic; Bleomycin; Cardiovascular Agents; Clozapine; Cyclophosphamide; Eosinophilia; Humans; Immunosuppressive Agents; Interleukin-2; Methotrexate; Methysergide; Nitrofurantoin; Penicillamine; Pleural Diseases; Pleural Effusion; Serotonin Antagonists

Topics: Antipsychotic Agents; Clozapine; Eosinophilia; Humans; Prognosis

While clozapine-associated agranulocytosis has received extensive attention, a number of recent publications have identified that the incidence of eosinophilia may also be of concern. This retrospective review identifies the incidence of eosinophilia within a group of people commencing clozapine at a large hospital in Australia.. The pathology reports of all people (n = 160) who commenced clozapine within a 3.5-year period were retrospectively reviewed for incidences of eosinophilia.. The incidence of eosinophilia was identified as 13%, comprising 17 males and four females. All cases of eosinophilia developed within 4 weeks of commencing clozapine. One male reached a peak eosinophil level of 9 x 10(9)/L, which resolved after clozapine was withdrawn. In all other cases, the eosinophilia resolved without intervention.. With a rate of eosinophilia at 13% in this population under review, and given that there have been reports of 25 cases of eosinophilic cardiomyopathy resulting in four deaths worldwide, clinicians should be alert to the incidence and sequelae of eosinophilia in people receiving clozapine treatment.

Topics: Adult; Aged; Antipsychotic Agents; Clozapine; Eosinophilia; Female; Humans; Incidence; Male; Middle Aged; Retrospective Studies

When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation.. Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine (N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial (olanzapine [N=19], quetiapine [N=15], or risperidone [N=16]).. Time until treatment discontinuation for any reason was significantly longer for clozapine (median=10.5 months) than for quetiapine (median=3.3), or risperidone (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation.. For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine's serious side effects.

Topics: Adult; Agranulocytosis; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Clozapine; Cross-Over Studies; Dibenzothiazepines; Drug Monitoring; Drug Resistance; Eosinophilia; Female; Follow-Up Studies; Humans; Male; Olanzapine; Piperazines; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Thiazoles; Treatment Outcome

The atypical antipsychotic clozapine carries a high risk of inducing agranulocytosis. We attempted to investigate whether eosinophilia during clozapine treatment has predictive value for subsequent neutropenia/agranulocytosis. One hundred and seventy-seven patients were studied in a prospective naturalistic design using haloperidol as the reference compound. Clozapine was found to differ from haloperidol in respect to their influence on neutrophil granulocytes. In the clozapine group patients with eosinophilia showed a decrease in neutrophil count (less than 2000/mm3 neutrophil granulocytes) significantly more often than patients without eosinophilia.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Biomarkers; Clozapine; Eosinophilia; Female; Haloperidol; Humans; Male; Middle Aged; Neutropenia; Prospective Studies; Schizophrenia

Myelotoxicity continues to hinder the widespread use of clozapine in the United States. It has been theorized that eosinophilia predicts later agranulocytosis and that agranulocytosis occurs due to an immunologic mechanism. Our study compares the rates of these dyscrasias in clozapine-treated patients and a control group.. Forty-one patients taking clozapine and 29 patients taking haloperidol were monitored for a period of 6 months. Rates of eosinophilia and neutropenia were compared between the two treatment groups.. Treatment-emergent eosinophilia occurred frequently in both haloperidol- and clozapine-treated patients. No significant difference was seen between groups in the incidence of eosinophilia and neutropenia.. We find no statistical difference between the rates of eosinophilia or neutropenia in haloperidol- and clozapine-treated patients. This study does not support the use of eosinophilia as a reliable predictor of neutropenia.

Topics: Adult; Clozapine; Double-Blind Method; Eosinophilia; Female; Haloperidol; Humans; Incidence; Male; Neutropenia; Probability; Retrospective Studies; Schizophrenia

Increasing reports have appeared of pleural effusion and peripheral eosinophilia associated with clozapine treatment. These reports describe the onset of pleural effusion from 2 to 5 weeks after initiation of clozapine. Here, we describe a case of a 28-year-old Chinese male who presented with pleural effusion and peripheral eosinophilia ∼17 weeks after initiation of clozapine. We discuss this delayed presentation and examine the potential significance of the patient's East Asian ethnicity. We recommend clinicians consider ethnicity and other factors that can affect the metabolism of clozapine when choosing a clozapine titration schedule and when monitoring during clozapine treatment.

Topics: Adult; China; Clozapine; Eosinophilia; Humans; Male; Pleural Effusion

Clozapine-related drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare adverse reaction. We aimed to screen a large pharmacovigilance database to identify clozapine-related DRESS cases, even if otherwise reported and provide a clinical overview. We screened spontaneous reports of clozapine-related DRESS syndrome in EudraVigilance database applying the European Registry on Severe Cutaneous Adverse Drug Reactions (RegiSCAR) criteria and scores to identify probable/definite DRESS syndrome cases. Clinical and demographic characteristics of included cases were provided and associations between RegiSCAR scores, and time to develop/recover DRESS were assessed. In a total of 262,146 adverse drug reactions reports for 75,190 clozapine-treated patients, 596 cases fulfilled RegiSCAR criteria; ultimately, 51 cases were rated as probable/definite DRESS according to RegiSCAR scores, of which 4 were previously published as case reports. The mean age of patients was 41.06 years (43.1% females), with 13 patients (25.5%) receiving reported co-medication with other DRESS culprit drugs. Median time between clozapine initiation and DRESS symptoms was 25 days. Clozapine dose was associated with days to develop symptoms (Spearman's ρ 0.40, p = 0.03). Organ involvement was reported in all cases followed by fever (n = 49; 96.1%) and eosinophilia (n = 47; 92.2%). Treatment involved clozapine discontinuation for 37 patients (72.5%), while 3.9% (n = 2) of cases ended fatally. Clozapine rechallenge was undertaken in 25 patients (49.0%). The screening of the EudraVigilance database revealed 47 novel clozapine-related DRESS cases, and only one was originally reported as DRESS. Clozapine-related DRESS may occur with clozapine monotherapy not only during dose titration, but also during maintenance treatment.

Topics: Adult; Clozapine; Databases, Factual; Drug Hypersensitivity Syndrome; Eosinophilia; Female; Humans; Male; Pharmacovigilance

To evaluate the incidence of clozapine induced haematological side effects among patients receiving clozapine.. Data of 333 patients who were on clozapine for a mean duration of 52.96 (45.18) months were reviewed for haematological abnormalities.. Clozapine is associated eosinophilia and thrombocytopenia, which are often benign and in majority of the patients these normalize with time.

Topics: Adolescent; Adult; Aged; Anemia; Antipsychotic Agents; Clozapine; Drug-Related Side Effects and Adverse Reactions; Eosinophilia; Female; Hematologic Diseases; Humans; Incidence; India; Male; Middle Aged; Neutropenia; Psychotic Disorders; Retrospective Studies; Schizophrenia; Thrombocytopenia; Young Adult

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; C-Reactive Protein; Clozapine; Eosinophilia; Female; Fever; Humans

Topics: Adult; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Monitoring; Eosinophilia; Humans; Lung; Male; Patient Care Management; Pulmonary Eosinophilia; Schizophrenia; Tomography, X-Ray Computed; Treatment Outcome

Eosinophilia has been associated with the use of clozapine. Where clozapine associated eosinophilia develops, and is associated with organ specific damage, clozapine is usually ceased. In cases of treatment associated eosinophilia without evidence of organ specific damage, clozapine would also typically be withdrawn. There are small numbers of reports in the literature describing patients who have had a successful rechallenge of clozapine having previously stopped treatment due to eosinophilia without associated organ specific inflammation. We report the case of a man who underwent a successful retrial of clozapine.. Case from authors' clinical practice reviewed.. We present the case of a young man with treatment resistant schizophrenia who underwent a successful re-challenge of clozapine, having previously ceased treatment due to an eosinophilia associated with treatment.. We believe that the current report provides further evidence that it may be unnecessary to cease treatment in all patients who develop an eosinophilia without organ dysfunction whilst on clozapine. Furthermore, where clozapine has been ceased due to an eosinophilia without evidence of organ specific inflammation, clozapine rechallenge with increased haematological monitoring should be considered.

Topics: Adult; Antipsychotic Agents; Clozapine; Eosinophilia; Humans; Leukocyte Count; Male; Schizophrenia

Topics: Adult; Antipsychotic Agents; Clozapine; Eosinophilia; Humans; Male; Schizophrenia

We report the case of a multiple drug interaction involving clozapine, antifungals and oral contraceptives, which resulted in an increased clozapine plasma level, pericarditis with pericardial effusion and eosinophilia in a young Caucasian woman. These symptoms and signs disappeared a few days after discontinuation of clozapine. At present, we are not aware of reports of clozapine-antifungals interaction, whereas there is only one other case report on the interaction between oral contraceptives and clozapine. The purpose of this case report is to show the risk of potentially serious adverse effects stemming from drug interactions involving medications routinely used in clinical practice.. A 29-year-old Caucasian woman diagnosed with a schizoaffective disorder was admitted to a psychiatric unit for acute psychosis (hallucinations, delusions and catatonic behavior). She denied smoking tobacco products and was on long-term oral contraceptives. During the first month of hospitalization she was treated with antipsychotics and for 1 week she took simultaneously fluconazole and miconazole gel, after being diagnosed with oral candidiasis. On the last day of antifungals treatment, 29 days after admission, clozapine was started with resolution of psychotic symptoms. After 3 weeks, her clozapine plasma level had increased to 542 ng/mL and eosinophilia was observed. She complained of nausea, vomiting and palpitations; echocardiography showed echocardiographic abnormalities and pericardial effusion. Oral contraceptives were discontinued and after 1 week clozapine was interrupted, with a complete resolution of side effects and pericardial effusion within 4 days.. Clozapine is metabolized by cytochrome P450. The use of inhibitors or other substrates of cytochrome P450, such as antifungals and oral contraceptives, can cause long-lasting interactions and clozapine toxicity. The Naranjo algorithm shows clozapine is a definite cause of pericarditis (score 9) and both clozapine-antifungals and clozapine-contraceptives interactions resulted probable (score 5) in Drug Interaction Probability Scale. A good knowledge on drugs that act as substrates, inhibitors or inducers of cytochrome P450 is mandatory. When those drugs are used in patients taking clozapine, blood level monitoring of clozapine should be recommended, since a lower dose of clozapine might be required to prevent clozapine toxicity.

Topics: Adult; Antifungal Agents; Antipsychotic Agents; Clozapine; Contraceptives, Oral; Drug Interactions; Eosinophilia; Female; Humans; Pericardial Effusion; Pericarditis; Psychotic Disorders; Tachycardia, Sinus

Mr. S is a 32-year-old male with schizophrenia. Due to poor responses to various antipsychotic medications, he was started on clozapine with the dose titrated to 300 mg/day during a 4-week period. The weekly checks of the complete blood cell count showed gradual increases in the eosinophil count from normal values to 4320 per mm(3). Mr. S did not have any symptoms except some increased salivation. Clozapine was suspended, and eosinophils gradually began to decline to the normal range. Clozapine was subsequently re-started and there were no changes in eosinophil counts. Mr. S exhibited improvement of symptoms but complained of acute auricular pain and increased salivation, 8 weeks after clozapine rechallenge. He also developed a swelling of his both parotid glands. The diagnosis of clozapine-induced parotitis was suggested. Symptomatic medication was prescribed with a favorable outcome.. We report a case of a patient who developed eosinophilia shortly after clozapine use, and then developed parotitis. There is debate in the literature over how to manage these complications of clozapine treatment. Generally they do not warrant clozapine discontinuation.

Topics: Adult; Antipsychotic Agents; Chlorpromazine; Clozapine; Eosinophilia; Humans; Leukocyte Count; Male; Parotitis; Schizophrenia

Clozapine has shown superior efficacy over other antipsychotics. However, its use is complicated by the development of life-threatening hematologic adverse effects.. This paper reports the incidence of clozapine-induced hematologic toxicity in Saudi Arab patients.. King Khalid University Hospital, Riyadh, Saudi Arabia.. Medical data of Saudi Arab hospitalized patients receiving clozapine was retrospectively reviewed during the period between August 2009 and August 2012. White blood cell (WBC) counts and differentials were recorded in a specific form to watch for any hematologic toxicity. The hematologic toxicities included in this report are: eosinophilia, thrombocytopenia, lymphocytopenia, and agranulocytosis/neutropenia/leukopenia combined.. Complete WBC count.. During the study period 147 charts were reviewed. The mean age of patients was 38 ± 11.42 years and 52 % were males. During the study period 61 patients (42 %) developed 82 blood dyscrasias. Sixteen patients (10.9 %) developed agranulocytosis, neutropenia and leukopenia combined, while nineteen patients (12.9 %) developed lymphocytopenia, and seven patients (4.8 %) developed thrombocytopenia. Eosinophilia developed in 40 patients (27.2 %). During the first 18 weeks of therapy with clozapine, 21 (26 %) hematologic side effects were developed.. The data collected in this study does appear to indicate there may be an increased incidence of blood dyscrasias in Saudi Arabs which warrants further, more detailed, study. It would be of concern to psychiatric clinicians if the case of a genetic predisposition to clozapine-induced blood dyscrasias were proven in the future.

Topics: Adult; Antipsychotic Agents; Clozapine; Drug Monitoring; Drug Therapy, Combination; Eosinophilia; Female; Hospitals, University; Humans; Incidence; Leukocyte Count; Leukopenia; Male; Medical Records; Middle Aged; Platelet Count; Retrospective Studies; Saudi Arabia; Severity of Illness Index; Thrombocytopenia

Although many patients with schizophrenia fail to respond adequately to trials of 2 or more antipsychotics, utilization of clozapine for these patients remains low, despite recommendations for its use by accepted treatment guidelines. Some experts estimate that 5-10 times more patients could benefit from clozapine than who are now receiving it. Learning how to manage the unique side effect profile of clozapine can potentially remove barriers to prescribing this agent and thus unlock its unique therapeutic efficacy for more patients.

Topics: Agranulocytosis; Antipsychotic Agents; Clozapine; Constipation; Diabetes Mellitus; Eosinophilia; Humans; Myocarditis; Neuroleptic Malignant Syndrome; Neutropenia; Practice Guidelines as Topic; Practice Patterns, Physicians'; Schizophrenia; Sialorrhea; Tachycardia; Weight Gain

Topics: Antipsychotic Agents; Clozapine; Eosinophilia; Humans; Male; Myocarditis; Schizophrenia, Paranoid; Time Factors; Treatment Outcome; Young Adult

To present a case of clozapine-induced peripheral and pleural fluid eosinophilia (PFE).. A 28-year-old man who was taking clozapine for bipolar disorder presented with a 2-week history of increasing shortness of breath. A large right-sided pleural effusion was identified, and eosinophilia was noted in peripheral and pleural fluid. An extensive workup ruled out other etiologies of PFE, and an objective causality assessment revealed that an adverse reaction to clozapine was probable. Clozapine was discontinued and the patient had complete resolution of symptoms, peripheral eosinophilia, and pleural effusion.. Drug-induced pleural disease is uncommon. Nearly 30 drugs have been implicated as causation of pleural disease. Much less common is PFE, with only 8 drugs implicated since 2004. Clozapine is a second-generation antipsychotic approved for treatment of resistant schizophrenia. It is often also used to treat bipolar disorder. Common adverse effects include tachycardia, somnolence, weight gain, and sialorrhea. Uncommon adverse reactions include pancreatitis and agranulocytosis. Through 2009, 11 cases of clozapine-induced pleural effusion, with and without polyserositis, have been reported; however, pleural fluid studies to demonstrate eosinophilia have not been done.. To our knowledge, this is the first documented report of clozapine-induced peripheral eosinophilia and PFE. Clinicians should consider clozapine as a possible cause of these reactions.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Eosinophilia; Humans; Male; Pleural Diseases

Clozapine is an antipsychotic agent used when patients experience excessive extrapyramidal side effects from other antipsychotic agents or for therapy resistant schizophrenia. However, clozapine is also known for its serious adverse effects e.g. granulocytopenia and agranulocytosis.. A 40-year-old male with known schizophrenia, presented with severe diarrhea and eosinophilia in the peripheral blood examination result, arising 2 weeks after starting clozapine. Histopathological examination demonstrated an eosinophilic colitis. After the patient discontinued clozapine, the symptoms disappeared completely.. Eosinophilic colitis is a rare adverse effect of clozapine. It is only possible to diagnose this using endoscopy and biopsy, so that the complaint is often not recognised. The exact pathophysiology underlying this eosinophilic colitis is not known.

Topics: Adult; Antipsychotic Agents; Clozapine; Colitis; Eosinophilia; Humans; Male; Schizophrenia

Topics: Adult; Antipsychotic Agents; Clozapine; Eosinophilia; Humans; Male; Schizophrenia, Paranoid; Treatment Outcome

Clozapine is known to induce neutropenia as well as agranulocytosis. Some cases of olanzapine- and risperidone-induced neutropenia and agranulocytosis have also been reported. We prospectively investigated schizophrenia patients treated with second generation antipsychotics with respect to alterations of white blood cell counts.. In an analysis of our drug monitoring program, we studied white blood cell counts in 104 patients receiving different second generation antipsychotics other than clozapine for at least six months and compared them with those of 28 patients receiving clozapine.. We found neutropenia (neutrophils <2 000/microL) in the mixed group in 17.6% and in 11.8% of patients treated with clozapine during the first 6 months. There was no statistically significant difference between those groups with respect to the risk to develop neutropenia during the investigation period. There was no case of agranulocytosis. Neutropenia was transient in all patients. Eosinophilia occurred in some patients that developed neutropenia later on but had no significant predictive value.

Topics: Adult; Antipsychotic Agents; Clozapine; Drug Monitoring; Eosinophilia; Female; Humans; Incidence; Leukocyte Count; Male; Neutropenia; Prospective Studies; Time Factors

To analyze cases of clozapine-induced myocarditis for clinical and diagnostic trends.. A case definition was developed by a multidisciplinary group using reports of myocarditis with clozapine submitted to the Australian Therapeutic Goods Administration. The definition uses for diagnosis either histology or the combination of new signs of cardiac dysfunction combined with a cardiac-specific diagnostic parameter occurring within 45 days of starting clozapine. Potential cases of clozapine-related myocarditis occurring between January 1993 and September 2008 and a comparative group of long-term clozapine users were documented from the patients' medical records.. Thirty-eight of 59 reviewed cases met the case definition. Three patients died, and the diagnosis for these was confirmed on cardiac histology. Nearly all of the remaining patients had persistent tachycardia and elevated troponin level. The time to onset was 14-22 days in all except 2 patients. Of the patients who survived, 66% (23 cases) had eosinophilia occurring 0-7 days (mean, 4.0) after the peak in troponin. C-reactive protein (CRP) level was elevated to above 100 mg/L (952 nmol/L) in 79% (23 cases), and some had elevated levels of CRP when troponin level was still normal. None of the control group (47 patients) met the case definition.. Eosinophil counts should not be relied on for diagnosis of clozapine-related myocarditis, but elevated CRP may be an early indicator of developing myocarditis. Patients starting clozapine should be actively monitored for myocarditis during the first 4 weeks, with extra care taken during week 3.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Aged; Antipsychotic Agents; Australia; C-Reactive Protein; Case-Control Studies; Clozapine; Echocardiography; Eosinophilia; Female; Fever; Gated Blood-Pool Imaging; Humans; Male; Middle Aged; Myocarditis; Tachycardia; Troponin

Topics: Antimanic Agents; Antipsychotic Agents; Clozapine; Drug Therapy, Combination; Eosinophilia; Female; Humans; Middle Aged; Pleural Effusion; Valproic Acid

Clozapine has proven effective in reducing morbidity and suicidality in chronic non-remitting patients with schizophrenia. Occasionally, despite good therapeutic response, clozapine must be stopped due to dangerous side effects such as agranulocytosis. Drug-induced eosinophilia is a non-dose-dependent side effect of clozapine. In cases of mild increments of eosinophils and if the patient is asymptomatic, there is no need to make an immediate decision. However, if the increment is severe and producing symptoms, withdrawing the probable causative drug is warranted. There is a possible association between eosinophilia and myocarditis, a life-threatening condition. The efficacy of corticosteroid therapy in the treatment of eosinophilia has not been clearly established. We present a case report where switching from clozapine to quetiapine maintained the improvement in clinical status, after remittance of eosinophilia.

Topics: Adult; Antipsychotic Agents; Clozapine; Dibenzothiazepines; Drug Hypersensitivity; Eosinophilia; Eosinophils; Humans; Leukocyte Count; Male; Patient Readmission; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Topics: Adult; Antipsychotic Agents; Clozapine; Eosinophilia; Humans; Male; Pericarditis; Schizophrenia

Topics: Antipsychotic Agents; Chemical and Drug Induced Liver Injury; Clozapine; Drug Resistance; Eosinophilia; Exanthema; Female; Fever; Humans; Middle Aged; Schizophrenia

Topics: Antipsychotic Agents; Blood Sedimentation; Clozapine; Colitis; Diarrhea; Eosinophilia; Fever; Humans; Male; Middle Aged; Schizophrenia

Topics: Antipsychotic Agents; Clozapine; Crohn Disease; Diagnosis, Differential; Eosinophilia; Eosinophils; Female; Gastroenteritis; Humans; Male

Clozapine, the first atypical antipsychotic, is indicated for the treatment of therapy-resistant schizophrenia. It needs to be monitored closely because of its well-known potential side-effects, especially agranulocytosis. We present a case of a middle-aged woman with chronic schizophrenia, who was treated with clozapine and developed a clinical syndrome of asymptomatic pancreatitis and eosinophilia within the fifth week of treatment. Asymptomatic pancreatitis has rarely been reported up to now and is not recognized as a typical side-effect of clozapine. In our opinion, pancreatic enzymes should be monitored especially in the first 6 weeks of clozapine treatment.

Topics: Adult; Amylases; Antipsychotic Agents; Clozapine; Eosinophilia; Female; Humans; Pancreatitis; Pancrelipase; Schizophrenia

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Eosinophilia; Humans; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors

Clozapine is a dibenzodiazepine derivative that is more effective than standard neuroleptic drugs in refractory schizophrenic patients, but its introduction in some countries was delayed by its propensity to cause blood dyscrasias. However, over the last ten years, different reports have clearly demonstrated that agranulocytosis and neutropenia can be easily prevented by means of strict hematologic surveillance. This article reviews the results of the first five years of the Italian Clozapine Monitoring System (ICLOS).. The hematologic parameters of 2,404 patients registered between 1995 and 1999 were collected in a central database, before the patients began clozapine-treatment, weekly for the first 18 weeks, and then monthly throughout the duration of therapy. On the basis of conventional criteria, different risk levels have been identified with total leukocyte <3. 0x10(9)/L and/or an absolute neutrophil count <1.5x10(9)/L leading to immediate discontinuation of the drug.. The analysis shows that 0.9% of the patients developed neutropenia and 0.7% agranulocytosis, mainly during the first 18 weeks of clozapine treatment. Drug discontinuation led to the normalization of hematologic parameters in all cases, and the use of growth factors reduced the risk of infectious complications. Transient leukocytosis and eosinophilia were also observed but these did not have any serious clinical effects.. The ICLOS study confirms that regular hematologic monitoring is highly effective in minimizing the incidence of clozapine-associated blood dyscrasias. The lower than initially expected rates of agranulocytosis and associated deaths are encouraging in view of the benefits of this drug in treatment-resistant schizophrenia and other neurologic disorders.

Topics: Adult; Agranulocytosis; Antipsychotic Agents; Clozapine; Eosinophilia; Female; GABA Antagonists; Granulocyte Colony-Stimulating Factor; Humans; Incidence; Italy; Leukocytosis; Male; Middle Aged; Neutropenia; Paraproteinemias; Retrospective Studies; Risk Factors; Schizophrenia; Serotonin Antagonists; Thrombocytopenia

Topics: Adult; Antipsychotic Agents; Clozapine; Drug Administration Schedule; Drug Hypersensitivity; Eosinophilia; Female; Humans; Neutropenia; Schizophrenia, Paranoid

This report describes a 48-year-old caucasian male with schizophrenia who developed hepatitis, hyperglycemia, pleural effusion, eosinophilia, hematuria and proteinuria early in clozapine treatment which resolved on drug discontinuation. The literature on similar cases is reviewed.

Topics: Antipsychotic Agents; Blood Cell Count; Chemical and Drug Induced Liver Injury; Clozapine; Eosinophilia; Hematuria; Humans; Hyperglycemia; Male; Middle Aged; Pleural Effusion; Proteinuria; Schizophrenia, Paranoid; Tomography, X-Ray Computed

Eosinophilia has been encountered from 0.2 to 61.7% in clozapine-treated patients, mostly with a transient course and spontaneous remission. There have been few reports, however, which have investigated a challenge with clozapine in patients previously showing eosinophilia. Two case reports are presented: the first with clozapine challenge after eosinophilia, the second under clozapine treatment and no previous haematological side effects. The challenge case showed eosinophilia with 1.2 10(9)/l (z = 1.79, p = 0.04) being followed by normalization despite clozapine continuation, whereas the maximum value reached 2.1 10(9)/l in the single episode case, with consecutive normalization and uninterrupted treatment. Eosinophilia caused by clozapine was observed in challenge, preceded by a faster neutrophil production and consecutive decrease (z = 2.27, p = 0.01). A challenge with clozapine was feasible and showed no clinical symptoms of eosinophilia.

Topics: Adolescent; Adult; Antipsychotic Agents; Clozapine; Depressive Disorder; Eosinophilia; Humans; Male; Schizophrenia; Treatment Outcome

Topics: Adult; Agranulocytosis; Antipsychotic Agents; Clozapine; Eosinophilia; Humans; Schizophrenia

Topics: Adult; Antipsychotic Agents; Cellulitis; Clozapine; Eosinophilia; Humans; Male; Pleural Effusion; Psychotic Disorders

Topics: Adult; Agranulocytosis; Antipsychotic Agents; Clozapine; Eosinophilia; Humans; Male

Topics: Agranulocytosis; Antipsychotic Agents; Clozapine; Eosinophilia; Humans

Topics: Adult; Chronic Disease; Clozapine; Eosinophilia; Eosinophils; Humans; Leukocyte Count; Male; Neutropenia; Schizophrenia

Four patients with diarrhea and eosinophilia associated with clozapine therapy are presented. In two cases clozapine therapy was interrupted but then restarted; all patients eventually tolerated clozapine well. A syndrome of clozapine-induced eosinophilic colitis is suggested.

Topics: Adult; Antipsychotic Agents; Clozapine; Colitis; Eosinophilia; Female; Humans; Male; Middle Aged; Schizophrenia

The aim of the study was to shed more light on the incidence and course of clozapine-induced transient white blood count (WBC) disorders.. In an analysis of our clozapine drug monitoring program, we evaluated the data of 68 patients receiving clozapine for the first time. Incidence rates were calculated by actuarial life table analysis. The potential influence of sex, age, dose, and plasma level was evaluated using discriminant analysis.. Two patients developed progressive neutropenia, leading to agranulocytosis in one case. We also found the following transient hematologic dysfunctions: neutropenia (22.0%), eosinophilia (61.7%), and leukocytosis (40.9%). One patient showed chronic leukocytosis. Additionally, minor changes in the number of lymphocytes, monocytes, and basophilic granulocytes were detected in the study population.. Hematologic side effects are frequently induced by the atypical antipsychotic clozapine. Next to agranulocytosis, a progressive and potentially lethal hematologic adverse effect, most of the WBC disorders are transient and appear to be harmless.

Topics: Actuarial Analysis; Adult; Agranulocytosis; Austria; Clozapine; Drug Monitoring; Eosinophilia; Female; Humans; Incidence; Leukocytosis; Male; Neutropenia; Prevalence; Prospective Studies; Schizophrenia

Eosinophilia associated with clozapine treatment has been reported in some studies and limited case reports. Because little is known regarding incidence, course, and relevance of this finding, clozapine therapy has been terminated prematurely in some patients with elevated eosinophil counts.. Records were reviewed on 118 consecutively hospitalized, acutely psychotic patients treated over a 1-year period with clozapine for at least 3 weeks. Demographic data were obtained on those patients, and white blood cell counts were analyzed. We reviewed the data for predisposing factors, associated medical findings, or clinical sequelae, and performed a two-sided Fisher's exact test to determine if sex or diagnosis was associated with a higher risk of developing eosinophilia. The literature pertaining to this blood dyscrasia and its relationship to clozapine was reviewed.. In our population, the cumulative incidence of eosinophilia among women was 23% (13/57), a statistically significant higher risk (p < .01) than that in men (7% [4/61]). In all cases, the eosinophilia was noted between Weeks 3 and 5 of treatment and resolved without medical or psychiatric complications.. Eosinophilia should be added to the list of commonly observed side effects of clozapine treatment. Women appear to be at significant risk. Eosinophilia usually occurs early in therapy, spontaneously resolves, and is not associated with any known complications. An otherwise healthy person with this blood dyscrasia may continue with treatment but should be monitored closely. Further investigation into this finding may provide insight into the mechanism of neutropenia and other adverse reactions to clozapine.

Topics: Acute Disease; Adult; Clozapine; Depressive Disorder; Eosinophilia; Female; Hospitalization; Humans; Incidence; Leukocyte Count; Male; Middle Aged; Psychotic Disorders; Risk Factors; Schizophrenia; Sex Factors

Topics: Adult; Clozapine; Diagnosis, Differential; Dose-Response Relationship, Drug; Drug Hypersensitivity; Eosinophilia; Fever of Unknown Origin; Humans; Male; Schizophrenia; Schizophrenic Psychology

Topics: Adult; Clozapine; Eosinophilia; Female; Finland; Humans; Schizophrenia

Topics: Adolescent; Clozapine; Eosinophilia; Female; Humans; Pancreatitis

Topics: Adult; Clozapine; Eosinophilia; Female; Humans; Schizophrenia

Topics: Adult; Clozapine; Eosinophilia; Humans; Leukocytosis; Male; Recurrence; Schizophrenia