Olanzapine Tablets

1. Pharmacotherapeutic classification: Olanzapine is an antipsychotic. ACT code N05AH03 (diazepine and oxazepine). 2. Olanzapine is an antipsychotic that acts on multiple receptor systems, thereby showing a wide range of pharmacological activities. 3. In preclinical studies, olanzapine showed affinity for the following receptors (Ki100nM); serotonin 5-HT2A/2C, 5-HT3, 5-HT6; dopamine D1, D2, D3, D4, D5; cholinergic muscarinic receptors M1-M5; alpha; 1 receptors; and histamine H1 receptors. Animal behavioral studies have shown that olanzapine's antagonistic effects on serotonin, dopamine and cholinergics are consistent with its receptor binding effects. It has been demonstrated in in vitro and in vivo models that olanzapine has a higher affinity for serotonin 5-HT2 receptors than for dopamine D2 receptors. Electrophysiological studies have shown that olanzapine selectively reduces the discharge of dopaminergic neurons in the mesolimbic system (A10), while having little effect on the striatal pathway (A9) involved in motor function. 4. In animal experiments, the reduction of conditioned avoidance responses is related to the antipsychotic activity of the drug, while the effect of causing rigidity is related to the motor side effects of the drug. Olanzapine can reduce conditioned avoidance responses at doses lower than those that cause rigidity. Unlike some other antipsychotics, olanzapine can enhance the response to anti-anxiety experiments. 5. Positron emission scanning (PET) studies on healthy volunteers after a single oral administration (10 mg) showed that olanzapine occupied more 5-HT2A receptors than dopamine D2 receptors. In addition, a SPECT study of schizophrenia patients revealed that patients who responded to olanzapine had a lower striatal D2 receptor occupancy rate than patients who responded to other antipsychotics such as risperidone, which was comparable to clozapine. 6. Two placebo-controlled studies of 2,900 schizophrenia patients with both positive and negative symptoms, as well as two of three active drug-controlled studies, showed that olanzapine was significantly superior to the control in improving both negative and positive symptoms.

Olanzapine

White coated tablets, light yellow to yellow after removing the coating.

1. Olanzapine is used to treat schizophrenia. 2. For patients who respond to initial treatment, olanzapine can maintain its clinical effect during maintenance treatment. 3. Olanzapine is used to treat moderate to severe manic episodes. 4. For patients with manic episodes who respond to olanzapine, olanzapine can be used to prevent the recurrence of bipolar disorder.

1. 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 5-20 mg/day according to the patient's clinical status. It is recommended that after appropriate clinical evaluation, the dose can be increased to above the conventional dose of 10 mg/day, with an interval of no less than 24 hours between dosing. The dose should be gradually reduced when olanzapine is discontinued. 2. Manic episode: The starting dose is 15 mg per day when used alone and 10 mg per day when used in combination therapy. Prevention of relapse of bipolar disorder: The recommended starting dose is 10 mg/day. For patients using olanzapine to treat manic episodes, the continuous treatment dose for prevention of relapse is the same as before. For new manic, mixed episodes or depressive episodes, olanzapine treatment should be continued (the dose should be adjusted appropriately when necessary), and adjuvant drugs should be combined to treat affective symptoms according to clinical conditions. During the prevention and treatment of schizophrenia, manic episodes and bipolar disorder, the daily dose can be adjusted accordingly within the range of 5-20 mg/day according to individual clinical conditions. It is recommended that the drug be used in excess of the recommended dose only after appropriate clinical re-evaluation, and the dosing interval should be no less than 24 hours. Olanzapine administration does not require consideration of food intake, and food does not affect absorption. The dose should be gradually reduced when olanzapine is discontinued. 3. Patients with renal and/or liver impairment: A lower starting dose (5 mg) should be considered for such patients. The initial dose for patients with moderate liver dysfunction (cirrhosis, Child-Pugh grade A or B) should be 5 mg, and the dose should be increased with caution. 4. Female patients compared with male patients: The starting dose and dose range for female patients generally do not need to be adjusted. 5. Non-smoking patients compared with smoking patients: The starting dose and dose range for non-smoking patients generally do not need to be adjusted. When more than one factor that slows metabolism (female, elderly, non-smoking) is present, a lower starting dose should be considered. When the dose needs to be increased, it should also be conservative.

Adults 1. Weight In clinical trials, the mean weight gain in olanzapine-treated patients was greater than that in placebo-treated patients. Clinically significant weight gain was observed in all baseline body mass index (BMI) categories. In long-term clinical trials (at least 48 weeks), the degree of weight gain and the proportion of patients in the olanzapine-treated group with clinically significant weight gain were higher than those in short-term clinical trials. The percentage of patients with weight gain exceeding 25% of baseline weight (ge; 10%) is common during long-term medication. 2. Glucose In clinical trials (52 weeks), the mean change in glucose was greater in the olanzapine group compared with the placebo group. Compared with placebo, the mean change in glucose was greater in patients with evidence of baseline glucose dysregulation (including those diagnosed with diabetes or those who met the criteria for hyperglycemia), and these patients had greater increases in glycated hemoglobin (HbAIc) than placebo-treated patients. The proportion of patients whose blood glucose changes increased from normal or borderline baseline levels to high levels increased over time. In an analysis of patients who completed 9-12 months of olanzapine treatment, the average blood glucose rate slowed down after about 6 months. 3. Blood lipids In a 12-week clinical trial, compared with patients in the placebo-treated group, patients treated with olanzapine had greater increases in mean fasting total cholesterol, LDL cholesterol, and triglyceride concentrations. Patients without evidence of baseline lipid disorders had greater fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides). No statistically significant differences were observed between olanzapine-treated and placebo-treated patients regarding fasting HDL cholesterol. In long-term clinical trials (at least 48 weeks), the proportion of patients whose total cholesterol, LDL cholesterol, or triglycerides changed from normal or borderline levels to high levels, or whose HDL cholesterol changed from normal or borderline levels to low levels, was greater than in short-term clinical trials. In an analysis of patients who completed 12 months of treatment, there was no further increase in mean non-fasting total cholesterol after approximately 4-6 months. 4. Prolactin In a controlled clinical trial (up to 12 weeks), compared with 10.5% of patients in the placebo group, 30% of patients in the olanzapine-treated group had elevated prolactin, and the vast majority of patients were mild. Prolactin levels in patients with schizophrenia decrease with continued treatment. Adverse events related to menstruation associated with increased prolactin are common (incidence 10%, ge; 1%), while adverse events related to sexual function and breast are uncommon (incidence 1%, ge; 0.1%). Prolactin levels in patients with other mental illnesses continue to increase with continued treatment. Adverse events related to sexual function are common (incidence 10%, ge; 1%), while adverse events related to breast and menstruation are uncommon (incidence 1%, ge; 0.1%). 5. Asymptomatic transient increases in liver transaminases, ALT/SGPT and AST/SGOT, are occasionally seen. 6. Eosinophilia Occasionally, asymptomatic eosinophilia is seen. 7. Adverse reactions in special groups: In clinical trials conducted in elderly patients with dementia and psychosis, very common (10%) adverse reactions associated with olanzapine treatment were abnormal gait and falls. In clinical trials conducted in elderly patients with dementia and psychosis, common adverse reactions associated with olanzapine treatment (10% and ge; 1%) were urinary incontinence and pneumonia. In clinical trials of patients with Parkinson's disease-related drug-induced psychosis (dopamine agonists), reports of worsening Parkinson's symptoms were common and more frequent than in the placebo group. Reports of hallucinations were also common and more frequent than in the placebo group. In these clinical trials, patients were required to take a fixed minimum dose of anti-Parkinson's disease medication (dopamine agonist) before starting the study and maintain this dose throughout the study. The initial dose of olanzapine was 2.5 mg/day, and the dose was gradually increased at the discretion of the investigator to a maximum dose of 15 mg/day. Adolescents (13-17 years) 1. The types of adverse reactions observed in adolescent patients treated with olanzapine were similar to those observed in adult patients treated with olanzapine. Although no comparative clinical trial design was conducted for adolescents and adults, data from adolescent clinical trials were compared with data from adult clinical trials. 2. The average weight gain in adolescents (median treatment course of 3 weeks, weight gain of 4.6 kg) is greater than that in adults (median treatment course of 7 weeks, weight gain of 2.6 kg). 3. In long-term clinical trials (at least 24 weeks), the degree of weight gain and the proportion of adolescent patients with clinically significant weight gain in the olanzapine treatment group were higher than those in short-term clinical trials and adult patients. 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, the average weight gain was most obvious in overweight or obese patients at baseline. 4. Compared with adult patients, adolescent patients treated with olanzapine had similar average increases in fasting blood glucose levels; however, the difference between the olanzapine group and the placebo group was greater in adolescents compared with adult patients. 5. In long-term clinical trials (at least 24 weeks), changes in blood glucose from normal baseline levels to high levels were uncommon (incidence 0.1%-1%). 6. Compared with adults, adolescents treated with olanzapine generally have greater mean increases in fasting total cholesterol, LDL cholesterol, and triglyceride levels; however, in short-term clinical trials, the differences between the olanzapine and placebo groups were similar in adolescents and adults. 7. Compared with adults, adolescents treated with olanzapine have a higher incidence of increased prolactin and a greater mean increase in prolactin levels.

Olanzapine is contraindicated in patients with a known hypersensitivity to any of the components of the product. Olanzapine is contraindicated in patients known to be at risk for narrow-angle glaucoma.

Precautions for children: There are no studies in people under 18 years of age. Precautions for pregnancy and lactation: 1. Pregnancy: There are no adequate controlled trials for pregnant women. Patients who are already pregnant or planning to become pregnant during olanzapine treatment should inform their doctors. Due to limited experience, this drug can only be used when the possible benefits outweigh the potential risks to the fetus. Mothers who use olanzapine in the last 3 months of pregnancy have rarely reported spontaneous reports of tremors, high muscle tone, lethargy and somnolence in their infants. 2. Lactation: In a lactation study of healthy women, olanzapine was excreted through breast milk. The average infant exposure (mg/kg) at steady state was estimated to be 1.8% of the maternal olanzapine concentration (mg/kg). If the patient takes olanzapine, it is recommended not to breastfeed. Precautions for the elderly: It is usually not necessary to consider using a lower starting dose (5 mg/day), but for elderly people over 65 years old, if there is a clinical indication, a lower starting dose should still be considered.

1. Potentially other drugs that affect olanzapine: Single doses of antacids (aluminum, magnesium) or cimetidine do not affect the oral bioavailability of olanzapine. However, co-administration of activated carbon can reduce the oral bioavailability of olanzapine by 50-60%. Fluoxetine (60 mg single dose or 60 mg/day for 8 consecutive days) causes a 16% increase in the maximum concentration of olanzapine and a 16% decrease in the average clearance of olanzapine. The magnitude of the effect is small compared to the overall variability between individuals, so routine adjustment of drug dosage is not required. Simultaneous smoking (the clearance of olanzapine is decreased by 33% and the terminal half-life of the elimination phase is prolonged by 21% in non-smokers compared with smokers) or taking carbamazepine (the clearance of olanzapine increases by 44% and the terminal elimination half-life is accelerated by 22% after taking carbamazepine) may induce the metabolism of olanzapine. Smoking and carbamazepine treatment induce the activity of P450-1A2. 2. Fluvoxamine is a P450-1A2 inhibitor that can significantly inhibit the metabolism of olanzapine. After administration of fluvoxamine, the Cmax of olanzapine in non-smoking women increased by an average of 54%, while that in smoking men increased by an average of 77%. The AUC values of olanzapine increased by an average of 52% and 108%, respectively. Therefore, for patients who are currently taking fluvoxamine or other P-450-1A2 inhibitors (e.g., ciprofloxacin), it is necessary to consider reducing the initial dose of olanzapine. For patients who are starting to use P-450-1A2 inhibitors, the dosage of olanzapine should also be appropriately reduced. 3. Potential effects of olanzapine on other drugs: In clinical trials of single-dose administration, olanzapine did not inhibit imipramine and desipramine (P450-2D6 or P450-3A/1A2), warfarin (P450-2C19), theophylline (P450-1A2), or diazepam (P450-3A4 and P450-2C19). There is no interaction when used in combination with lithium salts or biperiden. The inhibitory metabolic activity of olanzapine in vitro was tested using radionuclide-labeled chromatase, and the inhibition constants of olanzapine were found to be 3A4 (491mu;M), 2C9 (751mu;M), 1A2 (36mu;M), 2C19 (920mu;M), and 2D6 (89mu;M), while the plasma concentration of olanzapine was only about 0.2mu;M. Therefore, the maximum inhibition of olanzapine on the P450 system will not exceed 0.7%. The clinical significance of these findings is unclear. 4. In vitro studies using human liver microsomes found that olanzapine hardly inhibited the main metabolic pathway of valproate, glucuronidation. In addition, it was found that valproate had little effect on the metabolism of olanzapine in vitro. Daily co-administration of 10 mg of olanzapine for 2 weeks in vivo did not affect the steady-state plasma concentration of valproate. Therefore, when co-administered with olanzapine, there is no need to adjust the dose of valproate.

Protect from light and store in sealed container at 15-30℃.

2.5 mg

2.5mg: valid for 24 months. 5mg, 10mg: valid for 36 months