What Is Olanzapine/Fluoxetine?

Olanzapine tablets, the indication is that olanzapine is used to treat schizophrenia. For patients who have responded to initial therapy, olanzapine is able to maintain basic clinical results during maintenance therapy. Olanzapine is used in the treatment of severe manic episodes. Olanzapine can be used to prevent the recurrence of bipolar disorder in patients with manic episodes who are effectively treated with olanzapine.

Drug Name: Olanzapine tablets

Drug type: Prescription drugs, medicines for medical workers' injuries
Use classification: Other antipsychotics

Olanzapine warnings

WARNINGS Elderly patients with dementia-associated psychosis have an increased mortality rate-compared with placebo, elderly patients with dementia-associated psychosis are at increased risk of death when using atypical antipsychotics. Analysis of 17 placebo-controlled clinical studies in elderly patients with dementia-related psychosis (mean mode treatment time was 10 weeks) found that the risk of death in patients in the drug-treated group was 1.6 to 1.6 in the placebo-controlled group. 1.7 times. In a typical 10-week controlled clinical study, the mortality rate was 45% in the drug treatment group and 2.6% in the placebo control group. Although the causes of death vary, most die from cardiovascular disease (such as heart failure, sudden death) or infection (such as pneumonia). Reproxil (olanzapine) is not approved for the treatment of dementia-related psychosis (see [Notes])

Olanzapine tablets composition

Olanzapine chemical name: 2-methyl-4- (4-methyl-1-piperazinyl) -10H-thieno [2,3-6] [1,5] benzodiazine Chemical structural formula:

Molecular formula: C ₁₇ H ₂₀ N ₄ S
Molecular weight: 312.44

Olanzapine sheet traits

White coated tablets, pale yellow to yellow after removal of coating.

Olanzapine indications

Olanzapine is used to treat schizophrenia.
For patients who have responded to initial therapy, olanzapine is able to maintain basic clinical results during maintenance therapy.
Olanzapine is used in the treatment of severe manic episodes.
Olanzapine can be used to prevent the recurrence of bipolar disorder in patients with manic episodes who are effectively treated with olanzapine.

Olanzapine tablets specifications

(1) 2.5mg (2) 5mg (3) 10mg

Olanzapine tablets dosage

Schizophrenia:
The recommended starting dose of olanzapine is 10 mg / day, once a day, regardless of food intake.
During the treatment of schizophrenia, the daily dose can be adjusted to 5 ~ 20mg / day according to the clinical status of the patient. It is recommended that after appropriate clinical evaluation, the dose be increased to more than the regular dose of 10mg / day, with a lot of interval In 24 hours. The dose should be gradually reduced when olanzapine is discontinued.
Manic episode:
The starting dose is 15 mg daily when used alone, and 10 mg daily when combined
Preventing the recurrence of bipolar disorder:
The recommended starting dose is 10 mg / day. For patients treated with olanzapine for manic episodes, the continuous treatment dose to prevent relapse is the same as before. For new manic, mixed or depressive episodes, olanzapine treatment should be continued (the dose should be adjusted appropriately when needed), and adjuvant drugs should be combined to treat emotional symptoms according to clinical conditions.
In the prevention and treatment of schizophrenia, manic episodes and bipolar disorder, the daily dose can be adjusted within the range of 5-20 mg / day according to the individual clinical conditions. It is recommended that only after appropriate clinical reassessment More than the recommended dosage can be used, and the interval between dosing should not be less than 24 hours. Olanzapine should be administered without taking into account the food. Food does not affect absorption. The dose should be gradually reduced when olanzapine is discontinued.
Patients with impaired kidney and / or liver function:
For these patients, a lower starting dose (5 mg) should be considered. Patients with moderate liver dysfunction (cirrhosis, Child-pugh grade A or B) have a primary dose of 5 mg and should be cautiously increased.
Female patients compared to men:
The starting dose and dose range for female patients generally do not need to be adjusted.
Compared with non-smokers:
The initial dose and dose range for non-smokers generally do not require adjustment.
When there is more than one factor that slows metabolism (female, old, non-smoker), consideration should be given to lowering the starting dose, and it should be conservative when it is necessary to increase the dose.

Olanzapine tablets adverse reactions

[u] Adult [/ u]
Weight < br In clinical trials, the average weight gain of olanzapine-treated patients was greater than that of patients in the placebo-treated group. Clinically significant weight gain was observed in all baseline body mass index (BMI) classifications.
In the long-term clinical trials (at least 48 weeks), both the degree of weight gain and the clinically significant increase in the weight of patients in the olanzapine-treated group were higher than in the short-term clinical trials. Percentage of patients (10%) who gained more than 25% of their baseline weight with long-term medication are common.
Glucose < br In the clinical trial (52 weeks), compared to the placebo group, the mean change in glucose was greater in the olanzapine group.
Olanzapine compared to placebo showed an increase in mean glucose in patients with evidence of baseline glucose disorders (including those diagnosed with diabetes or those meeting the criteria for hyperglycemia) who had glycated hemoglobin compared to placebo-treated patients ( HbA1c) increased even more.
The proportion of patients whose blood glucose changes from normal or critical baseline levels to high levels increases over time. In an analysis of patients who completed olanzapine for 9-12 months, the average glucose growth rate slowed after about 6 months.
Blood lipids < br In the 12-week clinical trial, compared with patients in the placebo group, the mean increase in fasting total cholesterol, LDL cholesterol, and triglyceride was greater in patients treated with olanzapine.
Patients without evidence of baseline dyslipidemia had greater fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides).
Regarding fasting HDL cholesterol, no statistically significant differences were observed between olanzapine-treated patients and placebo-treated patients.
Proportion of patients with changes in total cholesterol, LDL cholesterol, or triglycerides from normal or critical levels to high levels or proportion of patients with changes in HDL cholesterol from normal or critical levels to low levels in long-term clinical trials (at least 48 weeks) Are larger than short-term clinical trials. In a patient analysis that completed 12 months of treatment, there was no further increase in average non-fasting total cholesterol after about 4-6 months.
Prolactin < br In a controlled clinical trial (up to 12 weeks), prolactin was elevated in 10.5% of patients in the olanzapine group compared with 10.5% of patients in the placebo group. Most patients are mild. Prolactin levels in patients with schizophrenia decline as treatment continues, adverse menstrual events associated with prolactin elevation1 are more common (incidence rate <10%, 1%), and sexual function and breast Adverse events were uncommon (incidence rate <1%, 0.1%). Prolactin levels in patients with other mental illnesses ² continue to increase as treatment continues. Prolactin-related adverse sexual events are more common (incidence rate <10%, 1%), and adverse effects on breasts and menstruation Events were uncommon (incidence rate <1%, 0.1%).
(1) Analysis of TESEs for up to 52 weeks of treatment.
(2) Bipolar depression, psychotic depression, refractory depression, borderline personality disorder and bipolar mania.
Liver transaminase <br /> Occasional asymptomatic transient liver transaminase elevations, ALT / SGPT and AST / SGOT.
Eosinophilia <br /> I occasionally have asymptomatic eosinophilia.
Adverse Reactions in Specific Groups: In clinical trials performed in elderly patients with dementia, the most common (10%) adverse reactions associated with olanzapine treatment are abnormal gait and falls. In clinical trials conducted in patients with dementia in elderly psychiatric patients, common olanzapine treatment (<10% and 1%, adverse reactions are urinary incontinence and pneumonia. In drugs related to Parkinson's disease (dopamine agonist) In clinical trials of patients with induced psychosis, reports of exacerbation of Parkinson's symptoms are more common and more frequent than in the placebo group. Illusion reports are also common and more frequent than in the placebo group. In these clinical trials, patients are required to start the study Take a fixed minimum dose of an anti-Parkinson's disease drug (dopamine agonist) and maintain this dose throughout the study. The initial dose of olanzapine was 2.5 mg / day, and the dose was gradually increased according to the investigator's judgment, with a maximum dose of 15 mg /day.
The following table summarizes the term and frequency of core adverse drug reactions identified during oral trials and / or intramuscular injection of olanzapine during clinical trials and / or after marketing:
Core adverse drug reactions observed with olanzapine formulations

[u] Youth (age 13-17) [/ u]
The types of adverse reactions observed in adolescent patients treated with olanzapine were similar to those observed in adult patients treated with olanzapine. Although adolescent and adult comparative clinical trial designs were not conducted, adolescent clinical trial data and adult clinical trial data were compared.
Adolescents (median course of 3 weeks, weight gain of 4.6 kg) gained more weight on average than adults (median course of 7 weeks, weight gain of 2.6 kg).
In long-term clinical trials (at least 24 weeks), both the degree of weight gain and the clinically significant increase in body weight of adolescent patients in the olanzapine treatment group were higher than those in the short-term clinical trials and the adult group. With long-term medication, about half of adolescent patients gained more than 15% of their baseline weight and about one third of adolescent patients gained more than 25% of their baseline weight. Among adolescent patients, average weight gain was most pronounced in overweight or baseline obese patients.
The increase in fasting blood glucose levels was similar in adolescents and adults treated with olanzapine; however, there was a greater difference between the adolescent olanzapine group and the placebo group compared with adult patients.
In long-term clinical trials (at least 24 weeks), changes in blood glucose from normal baseline levels to high levels are uncommon (incidence rate: 0.1% -1%).
Olanzapine-treated adolescents generally have greater increases in fasting total cholesterol, LDL cholesterol, and triglycerides compared to adults; however, in short-term clinical trials, the difference between olanzapine and placebo was in adolescent patients It is similar to adult patients.
Compared with adults, olanzapine treatment caused a higher incidence of prolactin elevation in adolescents, and the mean value of elevated prolactin levels was greater.
The following table summarizes the adverse drug reactions and their rates determined during clinical trials in adolescent patients (ages 13-17) only:

Olanzapine taboo

Olanzapine is contraindicated in patients who are known to be allergic to any component of this product. Olanzapine is contraindicated in patients known to be at risk for narrow-angle glaucoma.

Precautions for Olanzapine tablets

Rarely, hyperglycemia has been reported. Patients with a history of diabetes have rare ketoacidosis or coma, and several deaths have been reported. Some cases have reported previous weight gain, which may be a contributing factor, and appropriate clinical monitoring of diabetic patients and those with high risk factors for diabetes is recommended.
When olanzapine is suddenly stopped, the following acute symptoms rarely occur, such as sweating, insomnia, tremor, anxiety, nausea or vomiting (<0.01%). When olanzapine is discontinued, a gradual reduction is recommended.
Complications: Olanzapine has been shown to have anticholinergic activity in vitro, but events related to anticholinergic activity in clinical trials are very low. However, olanzapine has limited clinical experience in treating patients with comorbid conditions, and it is recommended that olanzapine be used with caution in patients with prostatic hypertrophy or paralytic intestinal obstruction and related conditions.
Olanzapine is not recommended for Parkinson's disease and psychosis associated with dopamine agonists. In clinical trials, it has been reported that Parkinson's symptoms worsen or that hallucinations are more common and frequent than placebo after taking olanzapine (see Adverse Reactions). The placebo is comparable. In these trials, patients were required to use the lowest starting effective dose of anti-Parkinson's drug (dopamine agonist) to maintain a stable state, and to maintain the same type and dose of anti-Parkinson's drug used throughout the trial. Olanzapine started at 2.5 mg / day and was adjusted to a maximum of 15 mg / day at the discretion of the investigator.
Olanzapine is not approved for the treatment of dementia-related psychosis and / or behavioral disorders, nor is it recommended for this particular type of patient because it increases the risk of mortality and cerebrovascular events. In a placebo-controlled clinical trial (6-12 weeks), subjects were elderly (mean age 78 years) with mental illness and / or behavioral disorders with dementia. Compared with placebo, patients treated with olanzapine experienced a two-fold increase in mortality (3.5% and 1.5%, respectively). However, there was no positive correlation between the death rate and the dose of olanzapine (average daily dose of 4.4 mg) or the cycle of treatment. Risk factors leading to increased mortality include age greater than 65 years, difficulty swallowing, sedation, malnutrition and dehydration, lung diseases (such as inhaled or non-aspiration pneumonia), or simultaneous benzodiazepine use. However, excluding these risk factors, patients treated with olanzapine still have a higher mortality rate than patients taking placebo.
In the same clinical study, cerebrovascular adverse events (CVAE, or stroke, transient ischemic attack) were reported, including deaths. The incidence of cerebrovascular adverse events in patients treated with olanzapine was three times that of placebo (1.3% and 0.4%, respectively). All patients with cerebrovascular adverse events treated with olanzapine and placebo had pre-existing risk factors. Risk factors for CVAE associated with olanzapine treatment include those older than 75 years and vascular / mixed dementia. The effectiveness of olanzapine has not been demonstrated in these trials.
In the treatment of mental illness, the improvement of the patient's clinical condition may take days or even weeks. Patients should be closely monitored during this period.
Lactose: Olanzapine tablets contain lactose.
Patients often experience transient asymptomatic elevations of liver transaminase ALT and AST during medication, especially early in treatment. Therefore, olanzapine should be used with caution in patients with elevated ALT and / or AST, in patients with symptoms or signs of liver impairment, in patients who have shown limited liver function, and in patients who have been treated with potentially hepatotoxic drugs. If there is an increase in ALT and / or AST during treatment, you should pay attention to observation and consider reducing the dosage. In cases where hepatitis has been diagnosed, olanzapine treatment should be discontinued. Hepatitis has rarely been reported after listing, and very few reports of bile obstruction or mixed liver injury have been received.
Lipid changes: In placebo-controlled clinical trials, adverse lipid changes were found in patients receiving olanzapine (see [Adverse Reactions]), and appropriate clinical monitoring is recommended.
Cardiovascular death: In a retrospective observational study, patients treated with atypical antipsychotics (including olanzapine) or classic antipsychotics had presumed sudden cardiac death compared to patients who did not take antipsychotics The increased risk is dose-related (the latter is almost twice as risky as patients without antipsychotics). In the post-marketing report of olanzapine, reports of sudden cardiac deaths are rare.
Similar to other nerve blockers, olanzapine is used with caution in patients with reduced white blood cells and / or neutrophil counts, and in patients with known neutropenia, drug-induced bone marrow suppression / toxic effects Patients with a medical history, patients with concomitant disease, radiotherapy or chemotherapy causing myelosuppression, and patients with eosinophilia or myeloproliferative disease. Thirty-two patients with a history of neutropenia or agranulocytosis associated with clozapine did not experience neutropenia after olanzapine treatment, and neutropenia was common when olanzapine was combined with sodium valproate Cytocytosis.
Information on the combined use of lithium salts and sodium valproate is limited. There is no clinical data on the combined use of olanzapine and carbamazepine, only pharmacokinetic studies have been performed.
Nerve blocker malignant syndrome (NMS): NMS is a potentially lethal disease associated with antipsychotic drugs. NMS has rarely been reported in patients treated with olanzapine. The clinical features of NMS are high fever, myotonia, altered consciousness, and autonomic nervous system instability (pulse and blood pressure irregularities, tachycardia, sweating, and cardiac rhythm disorders). Additional symptoms include elevated creatine phosphokinase, myoglobinuria (striated muscle lysis), and acute renal failure. If the patient's symptoms and signs suggest NMS, or if they show unexplained high fever without other clinical features of NMS, then all antipsychotics, including olanzapine, should be discontinued on average.
Olanzapine is used with caution in patients with a history of convulsions and factors with reduced convulsive thresholds. There are few reports of convulsions caused by olanzapine, and the vast majority of these cases have reported a history of convulsions and risk factors for convulsions.
Tardive dyskinesia: In a one-year or shorter controlled study, dyskinesia occurred less frequently in olanzapine treatment and was statistically significant. However, long-term medication will increase the risk of tardive dyskinesia. Therefore, if patients treated with olanzapine develop symptoms and signs of tardive dyskinesia, they should consider reducing the dosage or discontinuing the medication. These symptoms may worsen transiently or worsen after stopping treatment.
Considering the basic effect of olanzapine on the central nervous system, caution should be exercised when used in combination with other centrally active drugs or in patients with alcohol. Since isolated olanzapine exhibits a dopamine antagonistic effect, it may antagonize the effect of a direct or indirect dopamine agonist.
Orthostatic hypotension is occasionally reported in clinical trials of olanzapine in elderly patients. As with other antipsychotics, olanzapine is recommended to monitor patients' blood pressure regularly when treating patients over 65 years of age.
In clinical trials, clinically significant QTc interval prolongation (baseline QTcF 500 milliseconds) in patients receiving olanzapine was uncommon (0.1% -1%), and there was no statistical difference compared to placebo. But like other antipsychotics, olanzapine should be used with other drugs known to extend the QTc interval, especially in elderly patients, patients with congenital long QT syndrome, patients with congestive heart failure, myocardial hypertrophy, Patients with hypokalemia or hypomagnesemia.
The transient link between olanzapine treatment and the occurrence of venous embolism is rarely reported (<0.01%), and the link between the two has not been confirmed. However, since patients with schizophrenia are often associated with the risk of acquired venous embolism, all risk factors that may be related to venous embolism (such as immobilization of the patient) should be considered and preventive measures taken.
Because olanzapine may cause drowsiness, patients should exercise extreme caution when operating hazardous machinery, including motor vehicles.

Olanzapine tablets for pregnant and lactating women

Pregnancy:
There are not enough controlled trials in pregnant women. Patients who are pregnant or who are planning to become pregnant during olanzapine treatment should notify their doctor. Due to limited experience, this drug should only be used when the potential benefits outweigh the potential danger to the fetus.
Spontaneous reports of tremor, high muscle tone, lethargy, and lethargy were rare in mothers who used olanzapine during the third trimester of pregnancy.
breast-feeding:
In a breastfeeding study of healthy women, olanzapine was excreted through milk. The average infant exposure (mg / kg) at steady state is estimated to be 1.8% of the maternal olanzapine concentration (mg / kg). If the patient is taking olanzapine, breastfeeding is not recommended.

Olanzapine tablets for children

There are no studies in people under 18 years of age.

Olanzapine tablets for the elderly

It is generally not necessary to consider using a lower starting dose (5mg / day), but for elderly people over 65 years of age, if there are clinical indications, you should still consider using a lower starting dose.

Olanzapine tablets drug interactions

Other drugs that potentially affect olanzapine: A single antacid (aluminum, magnesium) or cimetidine does not affect the oral bioavailability of olanzapine. However, combined use of activated carbon can reduce oral bioavailability of olanzapine by 50 to 60%. Fluoxetine (single dose of 60 mg or 60 mg / day for 8 days) increased the maximum concentration of olanzapine by 16%, and the average clearance of olanzapine decreased by 16%. The magnitude of the effect is small compared to the overall degree of variability among individuals, so routine adjustment of drug dose is not required. Simultaneous smoking (non-smokers have a 33% reduction in olanzapine clearance and 21% longer half-life at the end of the phase compared to smokers) or carbamazepine (olanzapine clearance increases 44% after taking carbamazepine , The end elimination half-life is 22% faster) may induce olanzapine metabolism. Smoking and carbamazepine treatment induced P450-1A2 activity.
Fluvoxamine is a P450-1A2 inhibitor that significantly inhibits the metabolism of olanzapine. After giving fluvoxamine, the Cmax of olanzapine increased by an average of 54% in non-smoker women, and increased by an average of 77% in smoking men. The olanzapine AUC values increased by 52% and 108%, respectively. Therefore, for patients who are using fluvoxamine or other P-45-1A2 inhibitors (eg, ciprofloxacin), consideration should be given to reducing the initial dose of olanzapine. For patients who begin to use P-45-1A2 inhibitors, the amount of olanzapine should be appropriately reduced.
Potential effects of olanzapine on other drugs: Olanzapine does not inhibit imipramine and normipramine (P450-2D6 or P450-3A / 1A2) in a single clinical trial, warfarin (P450- 2C19), theophylline (P450-1A2) or diazepam (P450-3A4 and P450-2C19). No interaction with lithium salt or Bipperiden. The inhibitory metabolic activity of olanzapine in vitro was examined with a nuclide-labeled pigment enzyme, and the inhibition constants of olanzapine were found to be 3A4 (491 M), 2C9 (751 M), 1A2 (36 M), 2C19 (920 M), 2D6 (89 M ), And the plasma concentration of olanzapine is only about 0.2 M. Therefore, the inhibition of olanzapine on the P450 system will not exceed 0.7%. The clinical significance of these findings is unknown.
In vitro studies using human liver microsomes have found that olanzapine hardly inhibits glucosinolation, the major metabolic pathway of valproate. It was also found that valproate had little effect on the metabolism of olanzapine in vitro. The daily combined administration of 10 mg nitrogen in vivo for 2 weeks did not affect the steady-state plasma concentration of valproate. Therefore, when olanzapine is used in combination, there is no need to adjust the dose of valproate.

Olanzapine tablets overdose

Symptoms and signs:
When olanzapine is overdose, the most common symptoms (incidence rate 10%) include tachycardia, agitation / aggression to the industry, dysarthria, various extrapyramidal symptoms, and decreased levels of arousal (from sedation to coma). Other important manifestations of olanzapine overdose include death, cramps, coma, suspicious MMS, respiratory depression, shortness of breath, high blood pressure or hypotension, arrhythmia (less than 2% in overdose), and cardiopulmonary function inhibition Wait. The lowest lethal dose of olanzapine reported to date is 450 mg, but there are also reports of surviving olanzapine doses in excess of 2 g.
How to deal with olanzapine excess:
At present, there is no specific olanzapine antidote, and no emetic method is used. Conventional overdose treatment methods (such as gastric lavage and carbon washing) can be used. Olanzapine's oral bioavailability is reduced by 50-60% when given an activated carbon formulation. At the same time, important organs should be monitored and treated based on clinical manifestations, including management of hypotension, circulatory failure, and maintenance of respiratory function. Do not use epinephrine, dopamine, or other sympathomimetic agents with receptor agonistic activity, as receptor agonists can aggravate hypotension and require monitoring of cardiovascular function for possible arrhythmias. Patients should be closely and continuously monitored until normal.

Olanzapine clinical trial

Schizophrenia < br Two short-term (6-week) controlled clinical trials in inpatients meeting DSM-IH-R schizophrenia criteria have determined the efficacy of oral olanzapine in the treatment of schizophrenia. One of the studies established droperidol monotherapy as a positive control group, but the trial compared the overall clinically significant dose range of the two drugs. Various assessment tools were used in the trial, including the Concise Psychiatric Scale (BPRS), a general psychopathological questionnaire consisting of multiple items traditionally used to evaluate the effect of medications on schizophrenia, BPRS Psychiatric factors (concept disorders, hallucinations, suspicious and bizarre thinking content) are particularly suitable for evaluating patients with schizophrenia who are active in psychosis. The second traditional assessment tool is the Clinical Overall Impression Scale (CGI). It reflects the impression of observers who are more familiar and acquainted with schizophrenic performance on the overall clinical status of the patient. In addition, two scales just developed in recent years are used. One is a 30-item scale. The Symptom Scale covers 18 items of BPRS; the other is the Negative Symptom Scale. The following clinical trial summary summarizes the results in the following aspects: PANSS total score BPRS total score, BPRS psychiatric factor, PANSS negative symptom scale is SANS score; CGI severity, test results are as follows: (1) In a period In the 6-week placebo-controlled clinical trial, the olanzapine treatment group had two doses of 1 mg / day and 10 mg / day once a day. The 10 mg / day dose group received a total score of PANSS (including the total BPRS score calculated from it). , BPRS psychiatric factors, PANSS negative symptoms subscale and CGI severity score were better than the placebo group; but 1mg / day did not have this advantage. (2) In another 6-week placebo-controlled trial, the olanzapine treatment group was adjusted to three dose ranges, 5.0 ± 2.5 mg / day, 10.0 ± 2.5 mg / day, and 15.0 ± 2.5 mg / day, both Once a day, the two high-dose groups (the actual average doses were 12 and 16 mg / day, respectively) outperformed the placebo group in the total BPRS score, BPRS psychiatric factor, and CGI severity score; the highest-dose olanzapine group received a SANS score It is superior to the placebo group, and there is no obvious advantage in the high-dose group compared with the middle-dose group. Analysis of the subgroups (race and gender) found no difference in treatment preparation between these subgroups. In a longer clinical trial, adult outpatients (n = 326) who met the DSM-IV schizophrenia criteria and were stable with olanzapine for at least 8 weeks during the open treatment period were randomly assigned to continue use Current doses of olanzapine in the treatment group (range of 10-20 mg / day) or placebo. It was planned to observe the recurrence of patients during the 12-month follow-up period. The criteria for recurrence were increased BPRS positive symptoms or hospitalization. However, the test results met the criteria for early termination of the trial because the placebo group was similar to the olanzapine group. The specific recurrence rate is too high, and the main outcome index of this trial is the recurrence time. The olanzapine group is better than the placebo group. Therefore, for patients with stable disease for about 8 weeks and 8 months of follow-up observation period, olanzapine Better than placebo in maintaining efficacy.
Bipolar Disorder: A single treatmentin two short-term 3 and 4 week, placebo-controlled clinical trialsin patients with bipolar type I affective disorder with manic episodes and mixed episodes meeting DSM-IV criteria Given the efficacy of oral olanzapine in the treatment of acute manic or mixed episodes, patients in these clinical trials were with or without psychotic features and with or without a rapid cycling course. In these trials, the main assessment tool used to assess the symptoms of mania is the Young Mania Scale (Y-MRS), which has 11 entries and is traditionally used to evaluate mania symptoms (irritable, disruptive or The degree of aggression, sleep, increased sexiness, increased speech, increased activity, sexual interest, language into thinking disorder, thinking content, appearance, and self-knowledge), with scores ranging from 0 (no mania characteristics) to 60 (highest score). The main results of these trials indicate changes in the Y-MRS total score after baseline. The results of the clinical trials are as follows: (1) In a placebo-controlled clinical trial of 3 weeks, the dose range of olanzapine was 5 -20mg / day, once daily with a starting dose of 10mg / day. Olanzapine is better than placebo in the Y-MRS total score reduction value. In a clinical trial, olanzapine showed the same difference, but olanzapine was not superior to placebo in this outcome indicator, possibly due to sample size and intercenter differences. (2) In a 4-week placebo-controlled clinical trial, the dose range of olanzapine was 5-20 mg / day, once a day, with a starting dose of 15 mg / day, once a day, and a starting dose of 15 mg / Today, olanzapine is superior to placebo in the reduction of Y-MRS total score. (3) In another clinical trial, 361 patients met the criteria for manic or unisex seizures of DSM-IV bipolar affective disorder, and olanzapine 5-20 mg / The treatment was effective, and the patients were randomly divided into groups, one continued to use the same dose of olanzapine, and the other received a placebo to observe the recurrence. On day 59 of double-blind treatment, approximately 50% of patients in the olanzapine group terminated the trial; on day 23 of double-blind treatment, 50% of patients in the placebo group terminated the test. During the open treatment phase, the total Y-MRS score decreased to 12,21 Hamilton depression scale scores decreased to 8, then the treatment was considered effective, and the double-blind treatment period, the total score of Y-MRS or HAM-D21 increased] 15, or hospitalized because of mania or depression, are all diseased relapse. During the randomization period, the time to relapse was significantly longer in patients who continued taking olanzapine. Combined therapy-In two controlled clinical trials, the efficacy of oral olanzapine combined with lithium or valproate in the treatment of acute manic episodes was determined. Patients with DSM0-IV bipolar disorder disorder manic episodes or mixed The criteria for sexual manic episodes, with or without psychotic characteristics in patients with these clinical trials, and with or without rapid circulation disease, were as follows: (1) In a 6-week placebo-to-combination trial, 175 outpatients (Y-MRS 16 days) who did not completely control manic or mixed episodes with lithium or valproate were randomly divided into groups, and olanzapine was added to the original treatment. Or placebo, olanzapine (dose range 5-20mg / day, once daily, starting dose 10mg / day, combined with lithium salt or valproate (therapeutic drug concentration range 0.6-1.2mEq / L or 50 respectively -125g / ml) in the Y-MRS total score reduction value than lithium or valproate alone. (2) In a 6-week placebo-controlled combination trial, the service lithium or valproate will be served Treatment of 169 patients with manic or mixed episodes not completed Patients (Y-MRS 16 were randomly divided into groups, and on the basis of the original treatment drugs, olanzapine or placebo, olanzapine (dose range 5-20mg / day, once a day, starting dose 10mg / Today, the lithium salt or valproate is fully incorporated, and the lithium salt or valproate is superior to the Y-MRS total score reduction.

Olanzapine tablets pharmacology and toxicology

Pharmacological classification: Olanzapine is an antipsychotic and the ACT code is NO5AHO3 (diazepine and oxazapine). Olanzapine is an antipsychotic that acts on a variety of receptor systems and thus shows a wide range of pharmacological activities. In preclinical studies, olanzapine has shown affinity with the following receptors: serotonin 5-HT, cholinergic alkaloid receptors M1-M5; receptors; and histamine H1 receptors, animal behavior Studies have shown that olanzapine's antagonistic effects on serotonin and dopamine are consistent with its receptor binding effect. It has been demonstrated in vitro and in vivo models that the affinity ratio of olanzapine to serotonin 5-HT2 receptor is comparable to that of dopamine D2 receptor. High affinity. Electrophysiological studies have proven that olanzapine selectively reduces the discharge of dopaminergic neurons in the mesencephalic limbic system (A10), and has little effect on the striatum pathways involved in motor function. In animal experiments, it reduces the conditioned avoidance response It is related to the antipsychotic activity of the drug, and the effect of causing stiffness is related to the side effects of the drug. Olanzapine can reduce conditioned avoidance at doses that are less rigid than other antipsychotics. Olanzapine enhances the response to "anxiolytic" experiments. A positron emission scan study of healthy volunteers after a single oral dose showed that olanzapine occupies more 5-HT receptors than dopamine D2 receptors. In addition, a SPECT study of schizophrenia patients revealed Compared with patients who are effective with olanzapine and other antipsychotics, patients with effective olanzapine treatment have a lower striatum D2 receptor occupancy rate compared with clozapine. Two placebo-controlled studies of 2,900 schizophrenia patients with both positive and negative symptoms, and two of three active drug controlled studies showing improvement in positive symptoms of olanzapine Both were significantly better than the control. Acute (single-dose) toxicity: Symptoms of oral poisoning in rodents are characterized by the action of high-valence nerve blockers, reduced activity, coma, tremor, clonic convulsions, salivation, and weight gain and speed retardation, causing death The median dose was approximately 210 mg / kg and 175 mg / kg. Dogs can tolerate a single dose of up to 100 mg / kg. Clinical symptoms include sedation, ataxia, tremor, increased heart rate, breathing costs, diminished pupils, and decreased appetite. A single oral dose of 100 mg / kg in monkeys will lead to collapse and more High doses can cause a semi-coma. Toxicity upon repeated dosing; in a study of up to 3 months in mice and up to 1 year in rats and dogs, it was found that the main effect of olanzapine is the inhibitory effect on CNS, anticholinergic Energy and external hematological disorders, the inhibition of CNS will gradually develop tolerance. Growth parameters are reduced at high doses. Reversible changes consistent with increased prolactin in rats include significant declines in the ovaries and uterus, as well as morphological changes in the vagina and breast. Hematological toxicity; effects on hematological parameters were found in each animal, including dose-related reductions in mouse circulating white blood cells and non-specific reductions in circulating white blood cells in rats, but no evidence of bone marrow cell poisoning was found. Dogs treated with a trace of 8 or 10 mg / kg per day (total olanzapine exposure is 12 to 15 times higher than that of humans treated with 12 mg. Reversible granulocytopenia, thrombocytopenia, and anemia occur. No adverse effects on bone marrow hematopoietic progenitor cells and proliferative cells were found in dogs. Reproductive toxicity; olanzapine was not teratogenic. Sedative effects affected the mating performance of male rats. The dose of 1.1 mg / kg (3 times the maximum human dose) ) Affect the estrous cycle, giving rats 3 mg / kg (9 times the maximum human dose) affects their reproduction parameters, and a temporary decrease in fetal development is observed in the offspring of rats receiving olanzapine. Mutagenicity; standard tests for the total total dose range of olanzapine have no mutagenicity or mutagenicity on average, including bacterial mutation detection and in vitro and living mammalian testing. Carcinogenicity; based on studies in mice and rats It can be concluded that olanzapine is not carcinogenic.

Olanzapine tablets pharmacokinetics

Olanzapine is well absorbed after daily administration, reaching peak plasma concentration within 5-8 hours. Absorption is not affected by food. The absolute bioavailability of oral versus intravenous administration has not been determined.
Olanzapine is metabolized in the liver through binding and oxidation pathways. The main metabolite present in the circulatory system is 10-N-glucuronic acid, which does not cross the blood-brain barrier. The cytochrome enzymes P450-CYP1A2 and P450-CYP2D6 are involved in the formation of N-desmethyl and 2-hydroxymethyl metabolites, and these two metabolites show significant pharmacological activity in live animal experiments. The nitrogen level is small. The main pharmacological activity is derived from the parent drug olanzapine. After oral administration, the average terminal elimination half-life of olanzapine in health researchers varies by age and gender.
Compared with younger subjects, healthy elderly (65 years and older) had a longer mean elimination half-life (51.8hr and 33.8hr, respectively) and a slower elimination (17.5L / hr and 18.2L / hr, respectively). The observed pharmacokinetic variation in the elderly is within the variation range of other populations. 44 elderly patients with schizophrenia over 65 years of age were treated with 5-20 mg / day olanzapine without any special adverse events.
Olanzapine's pharmacokinetics are similar in adolescents (13-17 years) and adults. In clinical studies, the average exposure of olanzapine in adolescents was approximately 27% higher. Demographic differences between adolescents and adults include lower average weight and fewer adolescent smokers. These factors may be related to the observed higher average adolescent exposure.
The mean elimination half-life of women was somewhat longer than that of men (36.7 hr and 32.3 hr, respectively), and clearance was slowed (18.9 L / hr and 27.3 L / hr, respectively). However, olanzapine (5-20 mg) has been shown to be as safe in female patients (n = 467) as in male patients (n = 869).
Patients with renal failure (creatinine clearance <10ml / min) compared with healthy researchers on average elimination half-life (37.7h and 32.4hr) or drug clearance (21.1L / hr and 25.0L / hr, respectively) There were no significant differences. A mass conservation study showed that nearly 57% of radiolabeled olanzapine appears in urine, mainly as metabolites.
Compared with non-smokers (clearance half-life and removal rates were 48.8hr and 14.1L / hr, respectively), the mean elimination half-life (39.3hr) was longer in patients with smoking and mild liver impairment, and the clearance rate was 18.0L. / hr).
Non-smokers had a longer mean elimination half-life (38.6 hr and 30.4 hr, respectively) and reduced clearance (18.6 L / hr and 27.7 L / hr, respectively) compared to smoking patients (male and female).
Compared with young people, elderly patients, female patients compared with men, non-smokers and smokers have slower plasma clearance of olanzapine. However, the effects of age, sex, or smoking on olanzapine clearance and half-life were small compared to the overall variability among individuals.
No differences in pharmacokinetic parameters were found between the three populations in the study of Caucasians, Japanese people, and Chinese.
In a concentration range of about 7 to 1000 ng / mL, the plasma protein binding rate of olanzapine is about 93%, which mainly binds albumin and -acid glycoprotein.

Olanzapine tablets storage

Protected from light, sealed at 15-30 ° C.

Olanzapine Tablet Packaging

This product is packed in aluminum-plastic blister, 7 pieces, 14 pieces, 28 pieces, 56 pieces / box.

Olanzapine tablets

(1) 2.5mg; effective period is 24 months, (2) 5mg, 10mg effective period is 36 months.

Olanzapine Tablets

JX20070238 ^[1]