What Is a Schizophrenia Injection?

Long-acting olanzapine injection is a test formula that combines the atypical antipsychotic Zyprexa (R) (olanzapine) and parabensic acid (which produces a salt), which can convert olanzapine The drug effect is maintained for up to 4 weeks. For those with schizophrenia, long-acting injectable antipsychotics can improve results because they have difficulty sticking to daily treatment.

Long-acting olanzapine injection

Long-acting olanzapine injection is a test formula that combines the atypical antipsychotic Zyprexa (R) (olanzapine) and parabensic acid (which produces a salt), which can convert olanzapine The drug effect is maintained for up to 4 weeks. For those with schizophrenia, long-acting injectable antipsychotics can improve results because they have difficulty sticking to daily treatment.

Drug Name

Long-acting olanzapine injection

Whether prescription drugs

prescription

Dosage form

Injection

Athletes use with caution

Use with caution

Whether to include health insurance

Incorporate

"Some patients with schizophrenia have benefited from olanzapine drugs, but they still suffer from the disease because they can't persist for a long time," said David McDonnell, MD, a clinical researcher at Lilly. These studies were presented at the conference. Provide some insights on the role of long-acting olanzapine injection in the treatment of patients. Since the nature of schizophrenia is long-term and severe, and it is difficult to adhere to long-term treatment, and the number of drug distribution institutions is very limited, Therefore, if the long-acting olanzapine injection is approved, the preparation will be a very valuable treatment option. "

An independent regulatory review of long-acting olanzapine injections is about to begin between the European Union, Canada, Australia and the United States. At present, long-acting olanzapine injection is undergoing review by the European Union's Committee on Medicinal Products for Human Use (CHMP), and CHMP's opinion will determine whether the preparation can be submitted to regulatory authorities and obtain market licenses in various countries.

Introduction to HGKA (a 24-week efficacy study)

A total of 1,065 adult outpatients with schizophrenia participated in this 24-week double-blind maintenance study. The patients who had previously taken open oral olanzapine (10 mg, 15 mg, or 20 mg per day) for 4 to 8 weeks had stabilized their condition. They were randomly assigned to three groups, each receiving: a one of three doses of long-acting olanzapine injection (150 mg every 2 weeks, 300 mg every 2 weeks, or 405 mg every 4 weeks); b long-acting Low reference dose of azapine injection (45 mg every 4 weeks); c maintain their previous stable dose of oral olanzapine. No supplemental oral antipsychotics were allowed during the study.

Evaluation of clinical stability is based on changes in oral olanzapine doses and standard measures, including the "Clinical Efficacy Rating Scale-Improved Condition" (CGI-I) and the Concise Psychiatric Rating Scale (BPRS) ratings . Symptom severity is evaluated based on the Positive and Negative Symptom Scale (PANSS), the BPRS derived from the PANSS, and the Overall Clinical Efficacy Scale-Severity of the Condition (CGI-S) and " CGI-I "rating.

Studies have shown that the positive effects of long-acting olanzapine injections can last up to 6 months. Among patients receiving long-acting olanzapine injections (150 mg every 2 weeks, 300 mg every 2 weeks, and 405 mg every 4 weeks), the average change from the beginning to the end of the PANSS score was similar to that of those receiving the reference dose. Patients had significant differences (the ratio of the former and the latter were: 2.7, -2.2, -0.1 to 7.3; all p <0.001). Significant differences in total PANSS scores between the two groups receiving the treatment dose (150 mg every 2 weeks, 300 mg every 2 weeks, 405 mg every 4 weeks) and the reference dose (45 mg every 4 weeks) since the 11th week after the trial It started to appear on the 3rd, 2nd and 3rd weeks, and this situation continued until the end of the study (p <0.05).

Similar differences between the therapeutic and reference doses of long-acting olanzapine injections also appeared in the total BPRS score, CGI-I score, and CGI-S score. Oral olanzapine group PANSS total score from the beginning to the end of the average change (-1.7) and the group receiving the long-acting olanzapine injection of the highest change (-2.2, 300 mg every 2 weeks; p = 0.606) was not significant The difference was significantly higher than that of the other groups receiving long-acting olanzapine injections (p <0.01).

Except for injection-related cases, the safety record of long-acting olanzapine injection is consistent with oral olanzapine. During 6 months of treatment, the discontinuation rate was low. Patients receiving oral olanzapine (21.4%) and those receiving per-week olanzapine injections (8.3%, P less than or equal to 0.05), and those receiving each Patients treated with 150 mg long-acting olanzapine injection at 2 weeks (16.4%), patients treated with 300 mg long-acting olanzapine injection at 2 weeks (20.7%), and 405 mg long-acting olanzapine injection at 4 weeks Patients treated with fluid (15.2%,) gained 7% or more weight from baseline. The incidence of all injection site reactions, including injection pain, was 2.8%. Adverse reactions reported in more than 5% of patients include insomnia, weight gain, restlessness, nasopharyngitis, drowsiness, and headache. In HGKA, two patients developed post-injection syndrome with long-acting olanzapine injection, but both have fully recovered, including a series of sedative symptoms (severity ranging from mild to coma) and / or Symptoms of delirium (including confusion, obsession, restlessness, restlessness, and other cognitive impairments). Other symptoms include extrapyramidal symptoms, dysarthria, dyskinesias, aggressiveness, dizziness, fatigue, excessive tension, and convulsions.

Earlier this year, the Congress of the International Association for the Study of Schizophrenia (SIRS) disclosed data on primary endpoints for the recurrence of conditions related to this study. These data indicate that the relapse interval is longer for all high-dose patients receiving three long-acting olanzapine injections compared to those receiving the reference dose; and those receiving 405 mg every 4 weeks and 150 mg every 2 weeks Compared with patients treated with a 300 mg dose every 2 weeks, patients with oral olanzapine had similar relapse intervals.

As with all medications, there are risks associated with the use of long-acting injections. Throughout all clinical trials of long-acting olanzapine injections, long-acting olanzapine injections have shown similar safety to oral preparations, with the exception of cases related to injection and post-injection syndrome of long-acting olanzapine injections.

This analysis aims to study cases of post-injection syndrome of long-acting olanzapine injections in clinical trials of long-acting olanzapine injections to develop appropriate risk and medical management recommendations. The safety data collection of all completed and ongoing long-acting olanzapine clinical trials as of September 30, 2007 has been completed; the review of adverse event data as of May 31, 2008 has also been completed.

As of May 31, 2008, after using more than 40,000 long-acting olanzapine injections in 28 patients, the incidence of their syndrome was 29. According to statistics, the incidence was 0.07% per injection and 1.4 per patient. %, Or about one case per 1400 injections. No clinical signs of weakened vital signs were found, and all patients recovered completely within 1.5 to 72 hours, getting rid of the signs and symptoms of long-acting olanzapine injection syndrome. About 70% of patients continue to receive the injection after rehabilitation. The cumulative risk of a case of long-acting olanzapine injection syndrome after one year of treatment is 0.7% to 1.2%. (Because the injection interval is uncertain, these data represent only one range).

No other cases of long-acting olanzapine injection syndrome have occurred in all clinical trials as of July 31.

After extensive review of safety data from all clinical trials of long-acting olanzapine injections, and using knowledge of these cases as the main method of identifying and minimizing related symptoms, Eli Lilly proposed a comprehensive control of long-acting olanzapine injections. Comprehensive risk plan, including a detailed drug labeling, a post-injection observation period plan, and a training and education plan for a wide range of healthcare providers.

Brief introduction of long-acting antipsychotic injection

According to guidelines from the World Federation of Biological Psychiatric Associations (WFSBP), poor and partial adherence to treatment is a major problem in long-term treatment of schizophrenia. When patients are willing to receive this treatment because of convenience, and long-acting preparations can avoid the phenomenon of non-compliance of patients with oral drugs, long-acting preparations should be considered as an alternative treatment option. (2)

When using long-acting antipsychotics, treatment compliance has been improved, and treatment failure rates have been reduced. (3) By implementing long-acting drug therapy, the medical commissioner can know when the patient has received the drug treatment, and can quickly diagnose the patient's non-compliance when the patient does not receive the injection at the scheduled time. (4) Different from oral and short-acting injection preparations, long-acting antipsychotic preparations can maintain a stable and effective blood concentration of the active drug within the therapeutic range for a long period of time. (5)

Schizophrenia is a severe and debilitating disease with symptoms such as delusions (wrong beliefs cannot be corrected with reason), hallucinations (usually manifested as non-existent sounds or sights), disordered speech, and severe disorders or behaviors tension. These signs and symptoms are associated with significant impairments in social or occupational function. The constitutional characteristics of schizophrenia include that patients show typical signs and symptoms of the above category for most of the 1-month period, and some symptoms of the above category of disorders that last at least 6 months. (6) In addition to these symptoms, patients with schizophrenia are more likely to develop drug complications than the general population.

About Olanzapine

Since olanzapine was marketed in 1996, about 24 million patients worldwide have been treated with the preparation. Olanzapine should be used with caution in patients under 18 years of age.

In Europe, olanzapine is essential in schizophrenia and clinical trials, and can play a significant role in maintaining clinical efficacy in the continuous treatment of patients who show initial treatment effects. It is also essential for treating patients with moderate and severe manic episodes, and it can also be used to prevent bipolar disorder in patients with manic episodes who have achieved significant results after receiving olanzapine. Relapse.

Security Information

Olanzapine is rarely associated with symptoms such as exacerbation or worsening of hyperglycemia and / or diabetes associated with ketoacidosis or coma, including some fatal cases. In some cases, the use of the drug will first cause symptoms of weight gain, which may also be a trigger for the above symptoms. Appropriate clinical monitoring is a wise choice, especially for those with diabetes and those with risk factors for diabetes who are advised to receive regular blood glucose control.

Placebo-controlled clinical trials have observed adverse changes in blood lipids in patients treated with olanzapine. The average increase in fasting blood lipids (total cholesterol, low-density lipoprotein cholesterol, and triglycerides) was higher than those who had no signs of dyslipidemia at the start of treatment. Clinically, changes in blood lipids should be properly controlled, especially in patients with abnormal lipids and patients with risk factors for exacerbation of blood lipid disorders.

Over time, the number of patients with significant clinically adverse changes in weight gain, blood glucose, total / LDL / HDL cholesterol or triglycerides has also increased. After 9 to 12 months of treatment in adult patients, the average growth rate of blood glucose is lower than in patients treated for about 4-6 months.

As with all antipsychotics, patients receiving olanzapine rarely experience rare but potentially fatal Neuroleptic Malignant Syndrome (NMS). Once the onset of signs and symptoms of this disease occur, it is recommended to stop the medication immediately. The clinical symptoms of NMS are high fever, muscle stiffness, mental disorders, and autonomic disorders (pulse or blood pressure disorders, tachycardia, sweating, and arrhythmia). Other symptoms may include elevated creatine phosphokinase, myoglobinuria (striatum), and acute kidney failure.

At the same time, as with all antipsychotic treatments, olanzapine should be prescribed to meet the needs of minimizing tardive Dyskinesia (TD). The risk of exacerbation of tardive dyskinesia increases during treatment. Once the signs and symptoms of tardive dyskinesia are observed, you should consider reducing the dosage or stopping the medication. In addition, it should be noted that the above symptoms may worsen or even worsen after stopping the medication.

Other potentially serious adverse events include hypotension, convulsions, elevated prolactin levels, elevated liver enzymes, thromboembolism, neutropenia, sweating, insomnia, tremors, anxiety, nausea, or vomiting.

Patients with allergic symptoms to olanzapine and narrow-angle glaucoma cannot be treated with olanzapine. As the frequency of deaths and cerebrovascular accidents has been observed to increase clinically, patients with Alzheimer's-related psychosis and / or behavioral disorders cannot be treated with olanzapine. In addition, the drug cannot be used by patients with Parkinson's disease to treat dopamine agonists associated with psychosis.

In olanzapine treatment clinical trials, the most common adverse reactions in 1% or more of patients were drowsiness, weight gain, eosinophilia, prolactin, cholesterol, elevated blood glucose and triglyceride levels, diabetes, appetite, Dizziness, restlessness, Parkinson's disease, dyskinesia, orthostatic hypotension and increased anticholinergic symptoms, asymptomatic transient elevation of liver transaminase, rash, weakness, fatigue and edema.