Olanzapine Tablets Research Articles

A single-dose, randomized, two-way crossover study comparing two olanzapine tablet products in healthy adult male volunteers under fasting conditions

Background: Olanzapine is a psychotropic agent that belongs to the thienobenzodiazepine class. Objective: The aim of this study was to assess the bioequivalence of 2 commercial 10-mg tablet formulations of olanzapine by statistical analysis of the pharmacokinetic parameters C max, AUC from 0 to 72 hours after dosing (AUC 0-72), and AUC 0-∞ as required by the Egyptian health authority for the marketing of a generic product. Methods: This bioequivalence study was carried out in healthy male volunteers using a single-dose, randomized, 2-way crossover design under fasting conditions. Statistical analysis of the pharmacokinetic parameters C max, AUC 0-72, and AUC 0-∞ was conducted to determine bioequivalence (after log-transformation of data using analysis of variance and 90% CIs) and to gain marketing approval in Egypt. The formulations were considered to be bioequivalent if the log-transformed ratios of the 3 pharmacokinetic parameters were within the predetermined bioequivalence range (ie, 80%–125%), as established by the US Food and Drug Administration (FDA). Both the test product (Trademark: Integrol ® [Global Napi Pharmaceuticals, Cairo, Egypt]) and the reference product (Trademark: Zyprexa ® [Eli Lilly and Company, Basingstoke, Hampshire, United Kingdom]) were administered as 10-mg tablets with 240 mL of water after an overnight fast on 2 treatment days, separated by a 2-week washout period. After dosing, serial blood samples were collected for 72 hours. Plasma samples were analyzed using a sensitive, reproducible, and accurate liquid chromatography-tandem mass spectrometry method capable of quantitating olanzapine in the range of 0.167 to 16.7 ng/mL, with a lower limit of quantitation of 0.167 ng/mL. Adverse events were reported by the volunteers as instructed or observed by the resident physician, and were recorded, tabulated, and evaluated. Results: Twenty-four healthy adult male volunteers participated in this study. Their mean (SD) age was 24.7 (6.2) years (range, 19–41 years), mean weight was 73.4 (6.7) kg (range, 64–89 kg), and mean height was 174.25 (4.6) cm (range, 168–186 cm). Values for C max, AUC 0-72, AUC 0-∞, T max, t 1/2, and the terminal disposition rate constant were found to be in agreement with previously reported values. The differences between the 2 products did not reach statistical significance at P ≤ 0.05 (90% CIs: C max, 101.82–124.79; AUC 0-72, 93.36–102.04; and AUC 0-∞, 88.57–101.77). The test/reference ratio of these parameters was within the acceptance range of the FDA criterion for bioequivalence. Both formulations were apparently well absorbed from the gastrointestinal tract (ie, no specific gastrointestinal tract-related adverse events were reported). Conclusions: In this small study in healthy male volunteers, there were no statistically significant differences in any of the calculated pharmacokinetic parameters between the 10-mg test and reference tablets of olanzapine. The 90% CIs for the ratios of mean C max, AUC 0-72, and AUC 0-∞ were within the range of 80% to 125% (using log-transformed data), meeting the FDA regulatory criterion for bioequivalence. Both formulations were well tolerated.

Neuroleptic malignant syndrome developing after acute overdose with olanzapine and chlorpromazine

Neuroleptic malignant syndrome (NMS) is a relatively uncommon side effect that may develop after a recent increase in the therapeutic dose of an antipsychotic medication or the addition of a new agent in therapeutic doses. We report a case of NMS developing in a 36-year-old female patient 2 days following deliberate self-poisoning with 30 x 10-mg olanzapine tablets, 7 x 100-mg chlorpromazine tablets and an unknown amount of escitalopram. These were the patient's own medications. She had not been taking these for several weeks. The patient initially presented with sedation from her overdose which resolved over the next 24 hours. Following this, over the subsequent 24 hours, she became progressively confused, ataxic, hypertonic, ferbrile and tachycardic, with marked lead pipe rigidity of the limbs. Head CT, lumbar puncture and septic screen were all negative. She was treated with intravenous midazolam infusion, nasogastrically administered bromocriptine, external cooling and was mechanically ventilated. She gradually improved over a period of 10 days, with residual confusion lasting another week, and was discharged well with no deterioration from her premorbid neurologic state. To our knowledge, although there are numerous cases reported with therapeutic use, NMS has not been reported to develop following acute olanzapine overdose. Clinicians should be aware that this may be an uncommon side effect of antipsychotic medication.

Treating Mania in Wilson's Disease with Lithium

Treating Mania in Wilson's Disease with Lithium

Orally disintegrating olanzapine and potential differences in treatment‐emergent weight gain

Several papers and communications have reported possible weight reduction or less weight gain when patients start or switch to orally disintegrating olanzapine, as contrasted with standard oral olanzapine tablets. In this paper, the current literature is reviewed and hypothesized mechanisms of action are discussed. The data are still preliminary and mechanisms of action are not well understood. Randomized controlled trials are needed to further evaluate change in weight during treatment with orally disintegrating olanzapine.

Effectiveness and medication acceptance of olanzapine disintegrating tablets compared to standard olanzapine tablets in acutely treated psychiatric patients

This study compared effectiveness and acceptance of orally disintegrating olanzapine tablets (ODT) with standard-coated tablets (SOT) in acutely ill psychiatric patients admitted to psychiatric hospitals for emergency treatment. Large, prospective, observational study at hospital emergency units across Germany in patients with a diagnosis or tentative diagnosis of acute schizophrenia treated with ODT or SOT. Clinical (CGI-S and CGI-I) outcomes, attitudes towards medication (Nursing Assessment of Medication Acceptance, NAMA) scale, suicidal ideation, and adverse events were assessed at start of treatment and after 2 weeks. Both olanzapine formulations, ODT (N = 247) and SOT (N = 207), showed similar effectiveness after 2 weeks. CGI-I improved in 92.1% of patients (ODT: 91.8%, SOT: 92.3%). In patients receiving both formulations suicidal ideations were reduced (ODT from 53.9% to 20.6%, SOT from 51.2% to 22.7%). ODT was preferably given to severely ill (SOT: 49.8%, ODT: 64.4%) and aggressive patients. Adverse events were reported for 6.5% of ODT- and 2.9% of SOT-patients. This difference was possibly caused by the characteristics of patients receiving ODT. This non-randomized, observational study shows comparable outcomes and tolerability in patients treated with both olanzapine formulations. In an acute treatment setting, orally disintegrating tablets were preferably used for more severely ill and aggressive patients with low medication acceptance.

Lower weight gain with the orally disintegrating olanzapine than with standard tablets in first‐episode never treated psychotic patients

A post-hoc analysis of the data from a randomised clinical trial involving prescription of antipsychotic treatment to never treated first-onset psychotic patients was used to compare the weight change after 6-week olanzapine treatment (standard tablets vs. orally disintegrating formulation). In the subgroup of 38 patients randomised to olanzapine, standard olanzapine tablets were non-randomly and consecutively prescribed to the first 19 patients, with the orally disintegrating formulation being prescribed to the following 19 patients. After 6-week treatment with olanzapine, a significant higher increase in weight was noted in those patients on standard tablets (mean weight increase 6.3 +/- 1.9 Kg) as compared to those on orally disintegrating olanzapine (mean weight increase 3.3 +/- 3.2 Kg) (F = 7.7; p = 0.009). BMI increase was also significantly higher in the olanzapine tablet group (mean increase of 2.1 Kg/m(2) as compared with 1.1 Kg/m(2) in the orally disintegrating group) (F = 4.7; p = 0.036). Substantial weight gain (SWG) (> or =7% increase from baseline weight) was noted in 84.2% (n = 16) of the olanzapine tablet patients and in 31.6% (n = 6) of the orally disintegrating olanzapine patients, with the olanzapine tablet group showing a significant increase in the mean percentage of weight gain (F = 4.0; p = 0.014). Partial sublingual absorption occurring with orally disintegrating olanzapine may bypass gastrointestinal metabolisation and hence lead to differences in metabolite versus parent compound ratios. However, the need arises to replicate the present study with a longer follow-up.

P.3.c.008 Weight change after switching from olanzapine tablets to olanzapine orally disintegrated tablets in obese patients with schizophrenia

P.3.c.008 Weight change after switching from olanzapine tablets to olanzapine orally disintegrated tablets in obese patients with schizophrenia

Introduction: Methods, Commentary, and Summary

Objectives.Due to inherent dangers and barriers to research in emergency settings, few data are available to guide clinicians about how best to manage behavioral emergencies. Key constructs such as agitation are poorly defined. This lack of empirical data led us to undertake a survey of expert opini

Intravenous Valproate Use in Bipolar II Disorder After Gastric Bypass Surgery

Intravenous Valproate Use in Bipolar II Disorder After Gastric Bypass Surgery

P.2.062 The short-term effect of orally disintegrating olanzapine tablets on agitation and cooperation in clinical practice

P.2.062 The short-term effect of orally disintegrating olanzapine tablets on agitation and cooperation in clinical practice

27. Rapid Onset of Absorption with Olanzapine Orally Disintegrating Tablets

Orally disintegrating tablets (ODT) of olanzapine may be useful as an alternative formulation for acutely agitated patients and are favored by clinicians because of a clinical impression of rapid action. In a posthoc analysis, we evaluated olanzapine concentration profiles following ODT and standard oral tablets (SOT) to assess differences in absorption.

Reply: Treatment Noncompliance with Orally Disintegrating Olanzapine Tablets

Reply: Treatment Noncompliance with Orally Disintegrating Olanzapine Tablets

Orally disintegrating olanzapine: a possible alternative to injection of antipsychotic drugs.

1. The orally disintegrating formulation of olanzapine dissolves rapidly on contact with saliva. 2. In certain cases, orally disintegrating olanzapine may be administered, instead of injection of an antipsychotic agent. 3. Orally disintegrating olanzapine is intended to deliver a dose analogous to regular olanzapine tablets.

Dissolution profile, tolerability, and acceptability of the orally disintegrating olanzapine tablet in patients with schizophrenia.

This pilot study investigates the dissolution profile, tolerability, and acceptability of an orally disintegrating olanzapine tablet in patients with schizophrenia. Eleven patients with schizophrenia stabilized on oral olanzapine (mean dosage 12.7 mg daily [SD5.2]) were given an orally disintegrating olanzapine tablet, rather than their usual tablet, daily for 7 days. At each visit, visual assessments were made for elapsed time to initial disintegration (every 15 seconds) and complete disintegration (every 1 minute). At the end of the study, patients completed a drug-acceptance questionnaire. The mean time to initial disintegration was 15.78 seconds, and mean time to complete disintegration was 0.97 minutes. All patients found the orally disintegrating tablet acceptable and expressed positive comments. Nonserious clinically significant adverse events, asthenia, purpuric rash, headache, depression, and insomnia (preexisting, except for asthenia and insomnia) were reported in 3 patients. The orally disintegrating olanzapine tablet disintegrates rapidly and is a well-tolerated and acceptable alternative to standard olanzapine tablets in patients with schizophrenia.

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Acute olanzapine overdose

Olanzapine, a thiobenzodiazepine derivate, is a recently released novel antipsychotic medication. The authors report the first case of overdose of olanzapine in an apparent suicide attempt. A 38-year-old schizophrenic patient was brought to a hospital emergency room following the ingestion of 12 10-mg tablets of olanzapine. There were no serious clinical adverse effects. Copyright © 1999 John Wiley & Sons, Ltd.