clozapine and Intestinal-Obstruction

This study compared the bioequivalence of FazaClo (clozapine orally disintegrating tablets) 100 mg to Clozaril (clozapine standard oral tablets) 100 mg after multiple doses in patients with schizophrenia.. This was a randomized, open-label, multiple-dose study in which patients with schizophrenia received FazaClo or Clozaril 100 mg twice daily for 5 days before crossing over to the alternate therapy. Blood samples were obtained at regular intervals during and after the completion of treatment, and standard pharmacokinetic parameters were calculated. Safety and patient satisfaction with FazaClo were also assessed.. Thirty-six patients were enrolled, of whom 33 completed the study and 30 were included in the steady-state analyses. All pharmacokinetic parameters for clozapine and desmethylclozapine (the major metabolite of clozapine) were similar between FazaClo and Clozaril in both the completer and steady-state populations. Geometric mean values for steady-state maximum and minimum concentrations and area under the plasma concentration-time curve for FazaClo were all within 95-105% of those for Clozarilwell within the range considered by the US FDA as acceptable for bioequivalence (80-125%). Patients also expressed a high level of satisfaction with the FazaClo orally disintegrating tablet formulation.. FazaClo produced pharmacokinetic profiles almost identical to those of Clozaril. This should provide clinicians with reassurance that patients who receive FazaClo will achieve plasma drug concentrations similar to those produced by the same daily dose of Clozaril, and that no cross-titration is necessary when switching from one of these clozapine formulations to the other.

Topics: Administration, Oral; Adolescent; Adult; Antipsychotic Agents; Area Under Curve; Clozapine; Cross-Over Studies; Disorders of Excessive Somnolence; Dose-Response Relationship, Drug; Drug Administration Schedule; Drugs, Generic; Female; Half-Life; Humans; Intestinal Obstruction; Intestine, Small; Male; Metabolic Clearance Rate; Middle Aged; Patient Dropouts; Patient Satisfaction; Schizophrenia; Sweating; Tablets; Therapeutic Equivalency

The authors compared the effectiveness of initiating treatment with either clozapine or a standard antipsychotic among adults with evidence of treatment-resistant schizophrenia in routine clinical practice.. U.S. national Medicaid data from 2001 to 2009 were used to examine treatment outcomes in a cohort of patients with schizophrenia and evidence of treatment resistance that initiated clozapine (N=3,123) and in a propensity score-matched cohort that initiated a standard antipsychotic (N=3,123). Interventions were new initiation of clozapine or a standard antipsychotic medication, defined as no exposure to the new medication in the prior 365 days. The primary outcome was hospital admission for a mental disorder. Secondary outcomes included discontinuation of the index antipsychotic, use of an additional antipsychotic, incidence of serious medical conditions, and mortality.. Initiation of clozapine was associated with a significantly decreased rate of psychiatric hospital admission (hazard ratio=0.78, 95% CI=0.69-0.88), index antipsychotic discontinuation (hazard ratio=0.60, 95% CI=0.55-0.65), and use of an additional antipsychotic (hazard ratio=0.76, 95% CI=0.70-0.82). Clozapine was associated with significantly increased incidence of diabetes mellitus (2.8% for clozapine vs. 1.4% for standard antipsychotic; hazard ratio=1.63, 95% CI=0.98-2.70), hyperlipidemia (12.9% for clozapine vs. 8.5% for standard antipsychotic; hazard ratio=1.40, 95%CI=1.09-1.78), and intestinal obstruction (0.9% for clozapine vs. 0.3% for standard antipsychotic; hazard ratio=2.50, 95% CI=0.97-6.44).. In adults with schizophrenia and evidence of treatment resistance, initiating clozapine compared with initiating a standard antipsychotic was associated with greater effectiveness on several important outcomes. Increasing the judicious use of clozapine is warranted together with vigilance to prevent and detect serious medical adverse effects.

Topics: Adult; Antipsychotic Agents; Clozapine; Cohort Studies; Databases, Factual; Diabetes Mellitus; Female; Hospitalization; Humans; Hyperlipidemias; Intestinal Obstruction; Logistic Models; Male; Medicaid; Mental Health Services; Middle Aged; Proportional Hazards Models; Psychotic Disorders; Retrospective Studies; Schizophrenia; Treatment Outcome; United States

Topics: Adult; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Clozapine; Colectomy; Humans; Intestinal Obstruction; Male; Piperazines; Quinolones

Topics: Adult; Antipsychotic Agents; Aripiprazole; Clozapine; Defecation; Drug Substitution; Drug Therapy, Combination; Humans; Intestinal Obstruction; Lamotrigine; Male; Piperazines; Quinolones; Risk Factors; Schizophrenia; Treatment Outcome; Triazines

Schizophrenic women can now complete a pregnancy successfully, mostly due to psychiatric stabilization obtained with neuroleptic treatment. Side effects of classic neuroleptics are largely described in adults. On the other hand, effects of atypical neuroleptics, which are indicated when there is chronic severe schizophrenia with resistance or major intolerance to classic neuroleptics, are little known in newborn infants. We report the case of a hypertrophic full-term newborn whose mother received clozapine treatment alone with decreasing posology during the course of pregnancy. On his 2nd day of life, this newborn infant presented delayed peristalsis that required hospitalization in the digestive surgery department for more than 2 weeks. We assume that the anti-cholinergic effect of this molecule associated with a substantial plasmatic concentration and a possible increased half-life elimination were involved. Neonatal delayed peristalsis associated with clozapine treatment alone during pregnancy is poorly described in the medical literature. We only found one report on plasmatic concentrations of clozapine and its metabolite in a newborn, published in 1994. Close digestive monitoring is needed in the first days of life after in-utero exposure to clozapine and we believe that the question of a delayed initiation of enteral feeding after meconium elimination and in the absence of abdominal distension is debatable.

Topics: Adult; Antipsychotic Agents; Clozapine; Female; Humans; Infant, Newborn; Intestinal Obstruction; Male; Peristalsis; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Schizophrenia

Topics: Adult; Antipsychotic Agents; Clozapine; Colon; Colonic Diseases; Drug Therapy, Combination; Fatal Outcome; Fecal Impaction; Female; Humans; Intestinal Obstruction; Lung; Male; Middle Aged; Rectal Diseases; Rectum; Respiratory Aspiration; Schizophrenia

Topics: Antipsychotic Agents; Clozapine; Gastrointestinal Motility; Humans; Ileus; Intestinal Obstruction; New Zealand; United Kingdom

Topics: Adult; Antipsychotic Agents; Clozapine; Humans; Intestinal Obstruction; Male; Middle Aged

Topics: Adenocarcinoma; Adult; Cecal Neoplasms; Clozapine; Comorbidity; Humans; Intestinal Obstruction; Male; Postoperative Complications; Schizophrenia

Topics: Adult; Clozapine; Gastric Outlet Obstruction; Humans; Intestinal Obstruction; Male; Schizophrenia, Paranoid