Zyprexa Relprevv (olanzapine pamoate long-acting injection) / Eli Lilly, Cheplapharm - LARVOL DELTA

Patient and Healthcare Professional Attitudes and Trial Experiences with a Subcutaneous Long-Acting Injectable Olanzapine (TV-44749) for Schizophrenia Treatment. (PubMed, Adv Ther) - P3 | "Overall, this study highlights the differential value of TV-44749 and where it may address barriers associated with IM LAI olanzapine pamoate use. Additionally, these results provide insight into differences in attitudes and experiences among patients and HCPs regarding use of LAIs and help to identify opportunities where education could improve LAI adoption. Graphical plain language summary available for this article."

Journal • CNS Disorders • Psychiatry • Schizophrenia

Olanzapine for Extended-Release Injectable Suspension for Subcutaneous Use (TV-44749) Designed to Avoid the Risk of PDSS: In Vitro Release Studies in Human Plasma and In Vivo Impact of Extrinsic Factors on Pharmacokinetics. (PubMed, Pharmaceutics) - P3 | " To evaluate the robustness of the TV-44749 formulation, an in vitro release (IVR) study in human plasma was conducted, comparing TV-44749 to the commercially available intramuscular (im) long-acting injection formulation of olanzapine pamoate monohydrate. Additionally, in vivo rat studies found that manipulation of the injection site after TV-44749 administration, by either heating or rubbing at different time-points, resulted in no meaningful effect on overall olanzapine exposure. The presented findings support the robustness of the TV-44749 formulation in maintaining controlled-release properties, even under conditions that could otherwise compromise release performance."

Journal • PK/PD data • Preclinical • Anesthesia • CNS Disorders • Psychiatry • Schizophrenia

Cost-effectiveness analysis of treatment strategies initiating with second-generation antipsychotic long-acting injectables in patients with schizophrenia in the United States. (PubMed, J Manag Care Spec Pharm) - "To compare the cost-effectiveness of treatment strategies initiating with 4 SGA LAIs, aripiprazole monohydrate, aripiprazole lauroxil, olanzapine pamoate, and risperidone, with the strategy initiating with monthly paliperidone palmitate in patients with schizophrenia from the US health care sector perspective...Patients transitioned to additional lines of therapy (another SGA LAI and then clozapine) after relapse or intolerance to side effects...Sensitivity analysis confirmed the robustness of these findings, with LAI drug costs and relapse probabilities being the most influential parameters. Over a 5-year horizon, the treatment strategy initiating with paliperidone emerged as a favorable LAI option, providing the highest QALY gains at comparable or lower costs than the other LAI-initiating strategies."

Clinical • HEOR • Journal • CNS Disorders • Diabetes • Metabolic Disorders • Psychiatry • Schizophrenia

Efficacy and Safety of Olanzapine Long-acting Injection in Schizophrenia and Schizoaffective Disorder: A Systematic Review and Meta-analysis. (PubMed, Clin Psychopharmacol Neurosci) - "Based on low-certainty evidence from limited RCTs, olanzapine LAI appears comparable in efficacy and tolerability to oral olanzapine. It may be considered for patients with adherence difficulties, but careful safety monitoring is required and further head-to-head trials are needed."

Journal • Retrospective data • Review • Anesthesia • CNS Disorders • Psychiatry • Schizophrenia

Olanzapine long acting injectable in new application form-Hope for the absence of post-injection delirium/sedation syndromes (PubMed, Nervenarzt) - No abstract available

Journal • Review • Anesthesia • CNS Disorders

Selinexor (KPT-330) in Combination With Temozolomide and Radiation Therapy in Patients With Newly Diagnosed Glioblastoma (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jul 2026 ➔ Jul 2028

Trial completion date • Brain Cancer • Glioblastoma • Gliosarcoma • Oncology • Sarcoma • Solid Tumor

Preparing House Officers for Emergencies in a Psychiatric Setting with Simulation-Based Learning. (PubMed, Acad Psychiatry) - "Simulation-based learning was acceptable and increased the confidence of house officers managing emergencies in a psychiatric setting. Simulation-based learning can potentially improve the quality of care provided in psychiatric hospitals and the preparedness of new doctors entering these work environments."

Journal • Psychiatry

Cost-Effectiveness Analysis of Second-Generation Antipsychotic Long-Acting Injectables in Patients with Schizophrenia in the United States (ISPOR 2025) - "Our objective was to compare the cost-effectiveness of four intramuscular SGA LAIs (aripiprazole, aripiprazole lauroxil, olanzapine pamoate, and risperidone) to paliperidone palmitate in patients with schizophrenia from the US health care sector perspective...Patients transitioned to additional lines of therapy (another SGA LAI and then clozapine) when they experienced relapse or intolerance to side effects... Our estimation of 5-year costs and outcomes demonstrated similar total costs and QALYs across the SGA LAIs. Further studies to refine model inputs are needed to better differentiate between the SGA LAIs and to validate our findings."

Clinical • Cost effectiveness • HEOR • CNS Disorders • Psychiatry • Schizophrenia

Shortage antipsychotic medication supply hits vulnerable patients most (PubMed, Ned Tijdschr Geneeskd) - "The intramuscular depot of olanzapine (Zypadhera) was not available over a long period of time...Therefore, the medication shortages can have a life altering effect. As healthcare workers we feel obliged to report about the consequences of the severity of the rising number of medication shortages and highlight the consequences of the vulnerability of psychiatric patients."

Journal • CNS Disorders • Psychiatry

Clozapine-induced myocarditis – prevention, detection, and management (ECNP 2024) - "Recent findings indicate that the efficacy of clozapine re-initiation is superior compared to alternative approaches including treatment with olanzapine, long-acting injectable antipsychotics, and electroconvulsive therapy. To date, there is clear evidence for the singular importance of slow clozapine titration regimes to reduce side-effect rates. Importantly, combining this approach with a safe minimum CIM screening regime could increase global clozapine use. Finally, establishing a consensus regarding the minimal requirements for monitoring algorithms will aid in determining a balance between patient safety and the burden of CIM screening."

CNS Disorders • Pain • Psychiatry • Schizophrenia

Long-acting subcutaneous injectable olanzapine (TV-44749) demonstrates efficacy in patients with schizophrenia: Results from a randomised, double-blind, placebo-controlled trial (SOLARIS) (ECNP 2024) - P3 | "The Subcutaneous OLAnzapine extended-Release Injection Study (SOLARIS; NCT05693935) is an ongoing phase 3 study designed to assess the efficacy, safety and tolerability of TV-44749 in patients with schizophrenia. In patients with schizophrenia, once-monthly subcutaneous TV-44749 demonstrated significantly greater efficacy versus placebo with no reported PDSS. TV-44749 may provide an effective LAI olanzapine formulation while avoiding the risk of PDSS and will be further studied in the open-label, long-term safety period of SOLARIS."

Clinical • CNS Disorders • Psychiatry • Schizophrenia

Therapeutic drug monitoring of long-acting injectable antipsychotics and psychopathological assessment in schizophrenia spectrum disorders: a longitudinal characterisation of relapse risk (ECNP 2024) - "LAI antipsychotics were aripiprazole (41.3%), olanzapine pamoate (26.1%), paliperidone palmitate once monthly (13.0%), paliperidone palmitate every 3 months (19.6%)... The present study suggests a role for TDM in real-world practice, as finding under-range LAI plasma levels in clinically stable outpatients may prompt monitoring for relapses especially in younger patients. Moreover, the study suggests that relapses in patients with adequate LAI antipsychotic plasma levels may be tied to worse affective and negative symptoms, and to a worse subjective experience of treatment - underlining the need for a thorough psychopathological assessment beyond psychotic symptoms."

Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry • Schizophrenia

Safety and tolerability of TV-44749: Results from a randomised, placebo-controlled phase 3 trial in patients with schizophrenia (SOLARIS) (ECNP 2024) - P3 | "The Subcutaneous OLAnzapine extended-Release Injection Study (SOLARIS; NCT05693935) is an ongoing phase 3 study designed to assess the efficacy, safety and tolerability of TV-44749 in patients with schizophrenia. Results from Period 1 of the SOLARIS trial indicate that the safety profile of TV-44749 was consistent with other approved formulations of olanzapine, no new safety signals were identified, and there were no reported cases of PDSS. Safety and tolerability will be further investigated in the open-label, long-term safety period of SOLARIS."

Clinical • P3 data • CNS Disorders • Psychiatry • Schizophrenia

A long-acting subcutaneous injectable formulation of olanzapine is designed to eliminate the causes of post-injection delirium/sedation syndrome (ECNP 2024) - "Introduction Use of the intramuscular (im) formulation of olanzapine (Zyprexa Relprevv, Eli Lilly) has been limited because of a black-box warning of post-injection delirium sedation syndrome (PDSS) and associated REMS. Overall the sc route of administration and formulation characteristics of TV-44749 appear to eliminate the causes of PDSS. These Results are further supported by the lack of PDSS events in the phase 1 study."

CNS Disorders • Psychiatry • Schizophrenia

Olanzapine postinjection delirium/sedation syndrome after long-acting olanzapine depot injection presenting to the emergency department: practical guidelines for diagnosis and management. (PubMed, Emerg Med J) - "In this article, we give an overview of the current literature outlining the key aspects of managing this syndrome in a critical care setting, illustrated by a typical fictional clinical case. We discuss several useful and practical aspects of PDSS for emergency physicians and critical care physicians, including pharmacological background, common symptoms, diagnostic criteria and therapeutic options."

Journal • Review • Anesthesia • CNS Disorders • Critical care • Psychiatry • Schizophrenia

Acute Urinary Retention Associated with Olanzapine Long-acting Injection: A Case Report. (PubMed, Indian J Psychol Med) - No abstract available

Journal

TV-44749, A Long-Acting Subcutaneous (sc) Injectable Formulation of Olanzapine is Designed to Provide Sustained Controlled Concentrations and to Eliminate the Causes of Post-Injection Delirium/Sedation Syndrome (PDSS) (SIRS 2024) - "The results show that both APIs were stable in human plasma, however, olanzapine base in crystalline form II in TV-44749 showed 1.8 times lower solubility than olanzapine pamoate monohydrate of the IM formulation. For the IM formulation, 39% of olanzapine is released within first 0.5 h with complete release achieved within 24 hours. For TV-44749, only 3% of olanzapine is released within 4 hours and at the end of IVR experiment at 72 hours, only 14% of olanzapine is released."

CNS Disorders • Schizophrenia

Prevention, Detection, and Management of Clozapine-Induced Myocarditis (SIRS 2024) - "Moreover, recent findings indicate that the efficacy of clozapine re-initiation is superior compared to alternative approaches including treatment with olanzapine, long-acting injectable antipsychotics, and electroconvulsive therapy. Slowing clozapine titration rates and early routine use of therapeutic drug monitoring (TDM) can reduce the risk of dangerously fast increases in plasma clozapine levels which constitutes an established risk factor for CIM. Prescribers should also consider the pharmacokinetic effects of concomitant medication including valproate, olanzapine, and altered clozapine 2024 Congress of the Schizophrenia International Research Society metabolism related to changes in CYP1A2 enzyme activity due to inflammation. Additionally, stringent CIM screening and management ensure timely detection of CIM thus increasing patient safety and the chance for a restitutio ad integrum."

CNS Disorders • Schizophrenia • CRP • CYP1A2 • NPPB

In brief: Three new injectable antipsychotic drugs. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry • Schizophrenia

The SOLARIS protocol: a phase 3, randomized, double-blind, placebo-controlled trial assessing safety and efficacy of TV-44749 in adults with schizophrenia (ECNP 2023) - P3 | "When complete, this study will provide efficacy data (change from baseline to week 8 in PANSS, CGI-S, and PSP, among others) for multiple doses of once-monthly subcutaneous TV-44749, a LASCA olanzapine extended-release injectable suspension. Additionally, this study will provide safety and tolerability data and include active monitoring for PDSS events and other adverse events of interest (via AIMS, BARS, C-SSRS) for TV-44749 for the treatment of schizophrenia in adults."

Clinical • P3 data • CNS Disorders • Depression • Psychiatry • Schizophrenia

Clozapine in Combination With Olanzapine Long-Acting Injection: The Intersection of Treatment-Resistant Schizophrenia and Poor Medication Adherence-A Case Report. (PubMed, J Clin Psychopharmacol) - No abstract available

Adherence • Combination therapy • Journal • CNS Disorders • Psychiatry • Schizophrenia

Clozapine in Combination With Olanzapine Long-Acting Injection: The Intersection of Treatment-Resistant Schizophrenia and Poor Medication Adherence-A Case Report. (PubMed, J Clin Psychopharmacol) - No abstract available

Adherence • Combination therapy • Journal • CNS Disorders • Psychiatry • Schizophrenia

Real-world effectiveness of pharmacological treatments for bipolar disorder: register-based national cohort study. (PubMed, Br J Psychiatry) - "Lithium and certain LAI antipsychotics were associated with lowest risks of psychiatric admission. Lithium was the only treatment associated with decreased risk of both psychiatric and somatic admissions."

Journal • Real-world • Real-world effectiveness • Real-world evidence • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry

Evaluation of Patient Assistance Programs and Eligibility Criteria Offered for Long-Acting Antipsychotics Used in Patients With Schizophrenia (APA 2023) - "Of those, 70% (8/10) offer a PAP which covers the full cost for uninsured US residents, including: Abilify Maintena, Abilify Aristada, Invega Sustenna, Invega Trinza, Invega Hayfera, Risperdal Consta and Haldol Decanoate. With LAI’s such as Zyprexa Relprevv, Prolixin and Perseris being the exceptions... While these PAP’s cover the entirety of the cost of most of the available medications for those without insurance, they only aid a small subset of the population of patients suffering from schizophrenia. Efforts will need to be made to decrease the gap between costs of treatment and available financial assistance programs, especially for those expereincing financial difficulty who have some form of medical insurance and high copayments."

Clinical • CNS Disorders • Psychiatry • Schizophrenia

Evaluation of the REMs Programs for Psychiatric Medications (APA 2023) - "Conference participants will be engaged to discuss areas for improvement to the REMS programs for psychiatric medications. The speakers in the session will include two psychiatric pharmacists and a health services researcher.Learning Objectives Objective One: Describe Risk Evaluation and Mitigation Strategies (REMS) and provide an overview of the REMS programs for three psychiatric medications: esketamine, olanzapine pamoate, and clozapine Objective Two: Review a research protocol evaluating the three REMS programs Objective Three: Describe the perspectives of different healthcare professionals from the evaluation of the REMS programs Objective Four: Discuss recommendations and best practices for utilization of REMS programs for psychiatric medications so that members of the mental health team may better advocate for their clients Objective Five:"

Infectious Disease • Novel Coronavirus Disease • Psychiatry